WorldWideScience

Sample records for red-rumped agouti dasyprocta

  1. The lumbosacral plexus of the red-rumped agouti (Dasyprocta leporina Linnaeus, 1758 (Rodentia: Caviidae

    Directory of Open Access Journals (Sweden)

    Gleidson Benevides de Oliveira

    2016-12-01

    Full Text Available The red-rumped agouti is a small-sized wild rodent, belonging to the Dasyproctidae family, with great zootechnical potential, and it adapts well to captivity. In order to contribute to the species biology, this study describes the origin of the nerves forming the lumbosacral plexus. Twelve animals (six males and six females were used, from previous experiments. The animals were fixed in a 10% formaldehyde aqueous solution and eviscerated after 72 hours. Then, the major and minor psoas muscles were retracted, exposing the nerves forming the plexus. Cotton soaked with 20-volume hydrogen peroxide was placed on these nerves, remaining for 12 hours straight for bleaching and subsequent dissection. The topographical relations of the lumbosacral plexus were grouped into tables and arranged in terms of simple percentage. In 7 cases (58.34%, the lumbosacral plexus in the red-rumped agouti stemmed from the ventral roots of the last 4 lumbar nerves and the first 3 sacral nerves (Type I – L4-S3, in 4 animals (33.33% it stemmed from L5-S3 (Type II, and in 1 case (8.33% it stemmed from L5-S4 (Type III. The nerves participating of the lumbosacral plexus in the red-rumped agouti were: lateral femoral cutaneous, genitofemoral, femoral, obturator, sciatic, cranial gluteal, caudal gluteal, and pudendal nerve. The origin of the lumbosacral plexus and the spinal nerves making up this plexus in red-rumped agoutis were similar to that described in other rodents, such as rock cavy, lowland paca and spix's yellow-toothed cavy.

  2. The subplacenta of the red-rumped agouti (Dasyprocta leporina L)

    DEFF Research Database (Denmark)

    Rodrigues, Rosangela Felipe; Carter, Anthony M.; Ambrosio, Carlos Eduardo

    2006-01-01

    . Clusters of multinuclear giant cells occur in the transition zone between the subplacenta and decidua. There are prominent intercellular spaces between the cytotrophoblast cells. The basal membrane of these cells is often close to fetal blood vessels. The syncytiotrophoblast surrounds an extensive system....... We here describe the subplacenta of the red-rumped agouti and examine the possible functional correlates of this structure. METHODS: Placentae were collected from early in midgestation to near term of pregnancy and examined by standard histological techniques, immunohistochemistry and transmission...... electron microscopy. In addition, to study the microvasculature of the subplacenta, vessel casts were inspected by scanning electron microscopy. RESULTS: In the subplacenta, lamellae of connective tissue support a layer of mononuclear cytotrophoblast cells. Beneath this is found syncytiotrophoblast...

  3. Habitat use and relative abundance of the Spotted Paca Cuniculus paca (Linnaeus, 1766 (Rodentia: Cuniculidae and the Red-rumped Agouti Dasyprocta leporina (Linnaeus, 1758 (Rodentia: Dasyproctidae in Guatopo National Park, Venezuela

    Directory of Open Access Journals (Sweden)

    Elinor Jax

    2015-01-01

    Full Text Available The Spotted Paca Cuniculus paca and the Red-rumped Agouti Dasyprocta leporina are affected by habitat loss and hunting.  In Venezuela, their conservation status is unknown, even within protected areas.  The objective of this study was to estimate the relative abundance, activity patterns, habitat use, and effect of human activities on these species in Venezuela.  To achieve this, 26 camera-trap stations (20.8km2 were established in Guatopo National Park between February and April 2011, characterization of the habitat was undertaken and occupancy models were created.  The relative abundance of the Spotted Paca was 1.62 captures/100trap-nights, with a fully nocturnal activity pattern.  The relative abundance of the Red-rumped Agouti was 2.32 captures/100trap-nights, with a pronounced diurnal activity pattern. The occupation probability of the Red-rumped Agouti (0.61 SE 0.02 was higher than that of the Spotted Paca (0.27 SE 0.02. Spotted Pacas were mainly found in areas with mature forest and high tree density, whereas the  Red-rumped Agoutis were most frequently found in valleys with little disturbed forest.  A positive correlation was found between illegal hunting activities and areas occupied by the Spotted Paca.  It is important to strengthen the park control measurements to reduce illegal hunting of Spotted Pacas.

  4. The morphology of the pineal gland of the yellow-toothed cavy (Galea Spixii Wagler, 1831) and red-rumped agouti (Dasyprocta leporina linnaeus, 1758).

    Science.gov (United States)

    Câmara, Felipe Venceslau; Lopes, Igor Renno Guimarães; de Oliveira, Gleidson Benevides; Bezerra, Ferdinando Vinicius Fernandes; de Oliveira, Radan Elvis Matias; Oliveira Júnior, Carlos Magno; Silva, Alexandre Rodrigues; de Oliveira, Moacir Franco

    2015-08-01

    The pineal gland is an endocrine gland found in all mammals. This article describes the morphology of this important gland in two species of Caviideae, namely the yellow-toothed cavy and the red-rumped agouti. Ten adult animals of the two species used in current analysis were retrieved from the Center for the Multiplication of Wild Animals (CEMAS/UFERSA) and euthanized. The glands were removed and photographed in situ and ex situ. They were fixed in a paraformaldehyde solution 4% or glutaraldehyde 2.5% solution and submitted to routine histological techniques respectively for light and scanning electron microscopy. Macroscopically, the pineal gland with its elongated structure may be found between the cerebral hemispheres facing the rostral colliculi. Microscopically, pinealocytes and some glia cells were predominant. Contrastingly, to the cavy's pineal gland, a capsule covered the organ in the agouti, with the emission of incomplete septa to the interior, which divided it into two lobules. Light and scanning electron microscopes failed to show calcareous concretions in the pineal gland. Based on the topography of the cavy's and agouti's pineal gland, it may be classified as supra-callosum and ABC type. © 2015 Wiley Periodicals, Inc.

  5. The role of seed mass on the caching decision by agoutis, Dasyprocta leporina (Rodentia: Agoutidae

    Directory of Open Access Journals (Sweden)

    Mauro Galetti

    2010-06-01

    Full Text Available It has been shown that the local extinction of large-bodied frugivores may cause cascading consequences for plant recruitment and overall plant diversity. However, to what extent the resilient mammals can compensate the role of seed dispersal in defaunated sites is poorly understood. Caviomorph rodents, especially Dasyprocta spp., are usually resilient frugivores in hunted forests and their seed caching behavior may be important for many plant species which lack primary dispersers. We compared the effect of the variation in seed mass of six vertebrate-dispersed plant species on the caching decision by the red-rumped agoutis Dasyprocta leporina Linnaeus, 1758 in a land-bridge island of the Atlantic forest, Brazil. We found a strong positive effect of seed mass on seed fate and dispersal distance, but there was a great variation between species. Agoutis never cached seeds smaller than 0.9 g and larger seeds were dispersed for longer distances. Therefore, agoutis can be important seed dispersers of large-seeded species in defaunated forests.

  6. GASTROINTESTINAL PARASITES IN AGOUTI (Dasyprocta leporine PARASITAS GASTRINTESTINAIS DE CUTIAS (Dasyprocta leporina

    Directory of Open Access Journals (Sweden)

    Camila Belmonte Oliveira

    2008-04-01

    Full Text Available The objective of this work is reporting the parasitism in agouti (Dasyprocta leporine in Rio Grande do Sul, for that 24 samples of feces of animals originating from of a commercial creation were collected. The samples analyzed by the centrifugal-floating method presented different nematodes eggs and protozoaires of the genus Giardia and Eimeria. Keywords: Dasyprocta, parasitism, Giardia, Eimeria, helmints O objetivo deste trabalho é relatar o parasitismo em cutias (Dasyprocta leporina no Rio Grande do Sul, para isso foram coletadas 24 amostras de fezes de animais oriundos de uma criação comercial. As amostras analisadas pelo método de centrífugo-flutuação apresentaram diferentes ovos de nematóides e protozoários do gênero Giardia e Eimeria. Palavras - chave: Dasyprocta, parasitismo, Giardia, Eimeria, helmintos.

  7. Carrion consumption by Dasyprocta leporina (RODENTIA: DASYPROCTIDAE and a review of meat use by agoutis

    Directory of Open Access Journals (Sweden)

    L Figueira

    Full Text Available The consumption of the carrion of a tapiti by a reintroduced female Dasyprocta leporina was observed in the wild. Herein, besides describing this event, we reviewed other evidence of vertebrate consumption by agoutis. Most of the studies describing this behaviour have been carried out in captivity. The preyed animals included birds and small rodents, which were sometimes killed by agoutis. This pattern suggests that this is not an anomalous behaviour for the genus, reflecting its omnivorous habits. This behaviour can be a physiologically sound feeding strategy, so new studies should focus on the temporal variation in the consumption of this resource, possibly related to food scarcity periods or to reproductive seasons, when the need for high-quality food tends to increase.

  8. Computerized electrocardiogram in agoutis (Dasyprocta prymnolopha Wagler, 1831 anesthetized with ketamine and midazolam

    Directory of Open Access Journals (Sweden)

    Anaemilia N. Diniz

    Full Text Available ABSTRACT: An electrocardiogram is a test that assesses heart electrical activity and is applied more frequently in the veterinary care of wild animals. The present study aimed to define the electrocardiogram pattern of agoutis (Dasyprocta prymnolopha Wagler, 1831 anesthetized with ketamine and midazolam. Eighteen clinically healthy agoutis (D. prymnolopha were used from the Nucleus for Wild Animal Studies and Conservation (NEPAS of the Federal University of Piauí, Brazil. The animals were chemically restrained with 5% ketamine hydrochloride at a dose of 15mg/kg and midazolam at a dose of 1mg/kg by intramuscular injection. Electrocardiogram tests were carried out by a computerized method with the veterinary electrocardiogram [Acquisition Model for Computer (ECG - PC version Windows 95 Brazilian Electronic Technology (TEB consisting of an electronic circuit externally connected to a notebook computer with ECGPC-VET (TEB software installed on the hard disc. In analysing the EKG results, significant differences were observed for QRS complex duration, PR and QT intervals and for R wave millivoltage between the genders; but we observed a significant influence of weight despite the gender. In the present experiment, the anaesthetic protocol was shown to be well tolerated by the agoutis, and no arrhythmias occurred during the time the animals were monitored. The reference values obtained should be used to better understand the cardiac electrophysiology of the species and for its clinical and surgical management.

  9. Anatomical and histological characteristics of teeth in agouti (Dasyprocta prymnolopha Wagler, 1831

    Directory of Open Access Journals (Sweden)

    Daiane C. Baia da Silva

    2013-12-01

    Full Text Available The agouti species Dasyprocta prymnolopha (D. prymnolopha is a medium-sized rodent, diurnal, and characteristic of northeastern Brazil, south of the Amazon. Several studies have been made on these rodents. However, there is a lack of analysis of masticatory system, in particular morphology of the teeth. Thus, this research seeks to describe anatomical and histological aspects of the agouti teeth. For this purpose, we used adult agouti, in which measurements and descriptions of teeth and dental tissues were made. It was observed that the dental arch of D. prymnolopha comprises of twenty teeth, evenly distributed in the upper and lower arch, being inferior teeth larger than their corresponding higher. The incisors are larger, and between the posterior premolars and molars, there is a gradual increase in length in the anterior-posterior arch. In microscopic examination, a prismatic appearance was observed consisting of enamel prisms arranged in different directions, behind the enamel and dentin with standard tubular dentinal tubules with variable diameter and far between, also showing a sinuous path from the inner portion to the junction with more superficial enamel. Morphological analysis of dental tissues showed that an enamel with structural organization adapted to the act of chewing and high impact dentin compatible with standard tubular function resilience and mechanical damping of masticatory forces, as found in larger animals, confirming the understanding of eating habits that define much of its ecological functions within the ecosystem they inhabit.

  10. Interactions Among Different Devices and Electrical Stimulus on the Electroejaculation of Captive Agoutis (Dasyprocta leporina).

    Science.gov (United States)

    Castelo, T S; Souza, A L P; Lima, G L; Peixoto, G C X; Campos, L B; Oliveira, M F; Silva, A R

    2015-06-01

    The interactions among different electroejaculation devices associated with serial or continuous stimuli were investigated to improve the efficiency of the electroejaculation for semen collection in agoutis. Ten sexually matured male Dasyprocta leporina were restrained by the intramuscular administration of xylazine-ketamine association. Each individual was randomly subjected to four electroejaculation protocols, by combining two devices (one presenting longitudinal electrodes emitting square waves and other presenting ring electrodes emitting sine waves) and two electrical stimuli protocols (serial or continuous). A total of 40 attempts for electroejaculation were conducted in agoutis, being 10 per treatment. The most efficient treatment in providing ejaculates containing sperm (p electroejaculator connected to a probe with ring electrodes and associated with serial stimuli (4/7; 57%). In spite of semen parameters obtained by sine waves were adequate for using the samples for assisted reproduction, higher values for sperm motility and functional membrane integrity were obtained in the use of the square wave, independently of the electric stimulation protocol used (p electroejaculation in adults D. leporina. © 2015 Blackwell Verlag GmbH.

  11. Electrocardiogram assessment in non-anaesthetized clinically healthy agouti (Dasyprocta primnolopha, Wagler 1831

    Directory of Open Access Journals (Sweden)

    Anaemilia das N. Diniz

    2013-12-01

    Full Text Available The agouti is one of the most intensely hunted species throughout the Amazon and the semiarid regions of north-eastern Brazil. Considering the current tendency of wild animal management in captivity, the objective of this study was to determine heart reference values for agouti raised in captivity, based on electrocardiographic assessments (ECG. Adult agouti were selected without clinical signs of heart disease (n=30. The animals were restrained physically and then the ECG was performed. Standardized measurements were taken to establish the statistical analysis of the data. Analysis of the QRS complex showed values compatible with previous reports in peer animals and the limited data available for other wild and exotic species, except for the T wave that showed similar amplitude to the R wave in all the animals studied. The data obtained provided the first reference values for ECG tracings in agouti, contributing to a better understanding of heart electrophysiology in identifying myocardial pathology in these animals.

  12. CARDIOTHORACIC RATIO AND VERTEBRAL HEART SCALE IN CLINICALLY NORMAL BLACK-RUMPED AGOUTIS (DASYPROCTA PRYMNOLOPHA, WAGLER 1831).

    Science.gov (United States)

    de Moura, Charlys Rhands Coelho; das Neves Diniz, Anaemilia; da Silva Moura, Laecio; das Chagas Araújo Sousa, Francisco; Baltazar, Pollyana Irene; Freire, Larisse Danielle; Guerra, Porfírio Candanedo; de Sousa, João Macedo; Giglio, Robson Fortes; Pessoa, Gerson Tavares; de Sá, Renan Paraguassu; Alves, Flávio Ribeiro

    2015-06-01

    Wild rodents, such as the lowland paca (Cuniculus paca), capybara (Hydrochoerus hydrochaeris), rock cavy (Kerodon rupestris), guinea pig (Cavia aperea), and black-rumped agouti (Dasyprocta prymnolopha) are intensely hunted throughout Amazonia and at the semiarid regions of northeastern Brazil. To contribute to the preservation of these species, more information about their anatomy, physiology and pathophysiology is needed. The aim of this study was to standardize the vertebral heart scale (VHS) and cardiothoracic ratio (CTR) in clinically normal black-rumped agouti, as well as to compare the results of these two methods, which are commonly used to evaluate the cardiac silhouette in domestic animals. Twelve healthy black-rumped agoutis, divided into two groups (six males and six females), obtained from the Nucleus for Wild Animal Studies and Conservation at the Federal University of Piauí, were radiographed in right and left lateral and dorsoventral projections. The values of the VHS were 8.00±0.31v (the number of thoracic vertebral length spanned by each dimension, starting at T4) for males and 8.11±0.41v for females, and there was no statistical difference between the decubitus (right and left) or between males and females (P>0.05). The CTR mean values obtained were 0.51±0.03 for males, and 0.52±0.02 for females, and there was no statistical difference between the genders (P>0.05). However, there was positive correlation between VHS and CTR (r=0.77 right decubitus and r=0.82 left decubitus). The thoracic and heart diameter had mean values of 6.72±0.61 and 3.48±0.30 cm (males), and for the females, it was 6.61±0.51 and 3.5±0.30 cm, respectively, and there was statistical difference between the genders. The results demonstrated high correlation between the VHS and CTR producing similar results, indicating similar clinical precision for assessing the size of the cardiac silhouette in the black-rumped agoutis.

  13. Plasma concentration of progesterone and 17ß-estradiol of black-rumped agouti (Dasyprocta prymnolopha during the estrous cycle

    Directory of Open Access Journals (Sweden)

    Diva Anelie Guimarães

    2011-03-01

    Full Text Available Plasma concentration of progesterone and 17β-estradiol of black-rumped agouti (Dasyprocta prymnolopha during the estrous cycle. The agouti is a game animal that have been raised in captivity for conservation and sustainability purposes. However, the management of wild animals in an intensive breeding system requires an assertive knowledge of its reproductive parameters, one of the most important features for production improvement. Besides, little information is available regarding changes in reproductive hormone profiles in agouti. The objective of this study was to evaluate the hormonal profile of progesterone and 17β-estradiol during the estrous cycle of the agouti (Dasyprocta prymnolopha. The hormones were analyzed by radioimmunoassay. Blood samples were collected without sedation twice a week. The concentrations of progesterone were as follows: proestrus 0.78+0.39ng/ml, estrus 2.83+2.34ng/ml, metestrus 1.49+1.24ng/ml, diestrus 3.71+1.48ng/ml. In the estrous phase, an increase in the progesterone level was observed during a period of 24h. The average 17 β-estradiol levels were as follows: proestrus 2 030.98+961.00pg/ml, estrus 1 910.56+650.54pg/ml, metestrus 1 724.83+767.28pg/ml, diestrus 1 939.94+725.29pg/ml. The current results suggest that the progesterone plasma concentration during the estrous cycle in the agouti has a similar increasing, stabilizing and decreasing pattern, as in domestic mammals. Agoutis have two phases of follicular development, as two periods of 17β-estradiol peaks were observed, the first one in the metestrus and the second during the proestrus. Spontaneous ovulation seems to occur after the progesterone peak, possibly indicating that this hormone is associated with the ovulatory process. A more detailed investigation is needed for better understanding of how progesterone influences ovulation. Studies on the involvement of progesterone in follicular rupture can be carried out, using steroid biosynthesis

  14. Improving the efficiency of the preliminary electroejaculation technique developed for semen collection from the agouti (Dasyprocta leporina).

    Science.gov (United States)

    Mollineau, William M; Adogwa, Andrew O; Garcia, Gary W

    2010-12-01

    This study tested various combinations of ketamine and xylazine with the objective to improve on the efficiency of the preliminary electroejaculation technique developed for semen collection from the agouti (Dasyprocta leporina). There were two experiments, which were each replicated. Experiment 1 had six treatments: treatment 1 (30 mg/kg ketamine and 10 mg/kg xylazine), treatment 2 (20 mg/kg ketamine and 10 mg/kg xylazine), treatment 3 (30 mg/kg ketamine and 5 mg/kg xylazine), treatment 4 (20 mg/kg xylazine), treatment 5 (30 mg/kg xylazine), and treatment 6 (40 mg/kg xylazine). Experiment 2 included five treatments: treatment 7 (40 mg/kg xylazine), treatment 8 (20 mg/kg ketamine and 40 mg/kg xylazine), treatment 9 (15 mg/kg ketamine and 40 mg/kg xylazine), treatment 10 (10 mg/kg ketamine and 40 mg/kg xylazine), and treatment 11 (5 mg/kg ketamine and 40 mg/ kg xylazine). Mean induction times were 3:27 +/- 0:31 and 4:59 +/- 0.49; mean immobilization times were 1:55 +/- 0.11 and 1:19:06 +/- 0:11.7 hr, respectively, for experiments 1 and 2. Treatment 4 produced the best ejaculation time and semen volume, 4.53 +/- 0.52 min and 0.41 +/- 0.07 ml, respectively. Spermatozoa were observed in 75% of ejaculate samples collected when treatments 6 and 7 were applied. The best treatments were 6 and 7 (P electroejaculation.

  15. Colheita de sêmen por eletroejaculação em cutia-parda (Dasyprocta azarae Semen collection by electroejaculation in Azara´s agouti (Dasyprocta azarae

    Directory of Open Access Journals (Sweden)

    Antonio C. Martinez

    2013-01-01

    Full Text Available As cutias são animais que vivem nas Américas Central e do Sul, com potencial zootécnico e que despertam crescente interesse científico. O objetivo deste estudo foi estabelecer um padrão para colheita de sêmen por eletroejaculação em cutia-parda (Dasyprocta azarae. Foram utilizados machos adultos (n=4 anestesiados e submetidos a quatro séries de 20 estímulos eletroejaculatórios, com 3 segundos de duração cada, com uma intensidade de 2, 4, 6 e 8 volts, com dois minutos de intervalo entre cada série. A colheita de sêmen foi obtida em todos os animais, com ereção parcial com 2 volts, ereção evidente com 4 volts, ejaculação com 6 volts e exacerbação da glande e exteriorização das espículas penianas com 8 volts, observando-se espermatozoides em 100% das amostras. A técnica descrita para colheita de sêmen em cutia-parda foi eficaz.Agoutis are animals that live in South and Central America, present rearing potential and call increasing scientific interest. The aim of this paper was to establish a model for semen collection by electroejaculation in Azara´s agouti (Dasyprocta azarae. Anesthetized adult males (n=4 were submitted to four series of 20 electroejaculatory stimuli, during 3 seconds each and with 2, 4, 6 and 8 volts, with a 2 minutes rest among series. Semen collection was accomplished in every animal, with partial penis erection at 2 volts, makeable erection at 4 volts, ejaculation at 6 volts, glans and penis spines exposition at 8 volts, and sperm collected in all samples. The described technique for Azara's agouti semen collection was efficient.

  16. The quantification of testicular cells during the postnatal development in two Caviomorph rodents: the guinea pig (Cavia porcellus and the cutia (Dasyprocta agouti

    Directory of Open Access Journals (Sweden)

    LUCIANA S. SIMÕES

    2017-08-01

    Full Text Available ABSTRACT The germinative, Sertoli and Leydig cells of two caviomorph rodents (Cavia porcellus and Dasyprocta agouti were counted as well as the estimation of the total volume of the testis and the total volume of seminiferous tubules and interstitium in prepubertal, pubertal and adult animals. The number of spermatogonia, spermatocytes and spermatids cells increased during the pubertal phase in both rodents, notably the spermatid cells. The spermatocyte and spermatid slightly decreased in the adult of both rodents, but the increment in spermatogonia cells number was seen, mainly in cutias. The number of Sertoli cells increased in pubertal rodents, but in the adult the number reduced. Substantial number of Leydig cells was counted in pubertal and adult guinea pigs. In cutias, the number of Leydig cells increased in pubertal phase and decline in adults. The design-based stereological method has proven to be unbiased and reliable to be applied in reproduction studies.

  17. Organogenesis and foetal haemodynamics during the normal gestation of healthy black-rumped agoutis (Dasyprocta prymnolopha, Wagler, 1831) bred in captivity.

    Science.gov (United States)

    Sousa, Fca; Pessoa, G T; Moura, L S; Araújo, J R; Rodrigues, Rps; Barbosa, Maps; Diniz, A N; Souza, A B; Silva, E G; Lucena, L U; Sanches, M P; Silva-Filho, O F; Guerra, P C; Sousa, J M; Neves, W C; Alves, F R

    2017-02-01

    The objective of this study was to define the patterns of organogenesis and foetal haemodynamics during the normal gestation of healthy agoutis (Dasyprocta prymnolopha) kept in captivity. Thirty pregnant agoutis that ranged in size from small to medium and weighed between 2.5 and 3 kg underwent B-mode and Doppler ultrasonography for the biometric evaluation of the foetal organs. The foetal aortic blood flow proved to be predominantly systolic, and the measured flow velocity was 78.89 ± 2.95 cm/s, with a maximum pressure gradient of 2.12 ± 0.27 mmHg. The liver was characterized by its large volume, occupying the entire cranial aspect of the abdominal cavity, and it was associated cranially with the diaphragm and caudally with the stomach. The flow velocity in the portal vein was estimated to equal 12.17 ± 2.37 cm/s, with a resistivity index of 0.82 ± 0.05. The gallbladder was centrally located and protruded cranially towards the diaphragm. The spleen was visualized as an elongated structure with tapered cranial and caudal extremities, and the foetal kidneys were visualized bilaterally in the retroperitoneal region, with the right kidney positioned slightly more cranially than the left. The morphological characterization and hemodynamic analysis of the foetal organs of black-rumped agoutis via B-mode and Doppler ultrasonography allow determination of the vascular network and of reference values for the blood flow required for perfusing the anatomical elements essential for maintaining the viability of foetuses at different gestational ages. © 2016 Blackwell Verlag GmbH.

  18. Thoracic and heart biometrics of non-anesthetized agouti (Dasyprocta primnolopha Wagler, 1831 measured on radiographic images

    Directory of Open Access Journals (Sweden)

    Anaemilia das N. Diniz

    2013-03-01

    Full Text Available The agouti is a species intensively hunted throughout the Amazon and the semi-arid regions of northeastern Brazil. Considering the current trend in conservation management of wild species, the aim of this study was to determine the morphometric reference to the heart of agouti raised in captivity, based on thoracic and cardiac measurements in these animals. Thirty adult agoutis, 1 to 3 years of age, without clinical signs of cardiac disease were selected. The animals were physically restrained and radiographies in laterolateral (LL and ventrodorsal (VD recumbence were produced. The following measures were taken: the apicobasilar length of the heart (at the most cranial height of the Carina region to the heart apex (AB, maximum width of the heart perpendicular to AB (CD, heart inclination angle (AIC, trachea inclination angle (AIT, distance from the right heart wall (DPTd, distance from the left heart wall (DPTe and vertical depth of the thorax, and the ventral face of the vertebral column to the dorsal border of the sternum at the level of the trachea bifurcation (H. The ratios between AB/CD, AB/H and CD/H were also analyzed. To calculate the vertebral heart scale (VHS, the AB and CD measurements were laid over the thoracic vertebra starting at T4. Radiographic evaluation showed values consistent with those reported in small animals and some wild and exotic species. The main biometric values in the chest cavity and heart of agouti are arranged as follows: (1 The ratios between AB/H ratio and CD/H were not sensitive for identifying heart increases (p>0.05, while the ratio AB/CD was more sensitive in this identification (p<0.05; (2 AIC: 21.2±6.4º (mean between male and famale; (3 AIT for males and females: 9.93±3.23° and 8.4±3.94°; (4 DPTd and DPTe for males: 0.97±0.40cm and 0.7±0.30cm; (5 DPTd and DPTe for females: 1.12±0.42cm and 01.02±0.43cm; (6 VHS for males and females: 7.75±0.48v e 7.61±0.34v; (7 The caudal vena cava (CVC was

  19. Isolation, expansion and differentiation of cellular progenitors obtained from dental pulp of agouti (Dasyprocta prymnolopha Wagler, 1831

    Directory of Open Access Journals (Sweden)

    Yulla K.P. de Carvalho

    2015-06-01

    Full Text Available Abstract: The study aimed to isolate, expand, differentiate and characterize progenitor cells existent in the dental pulp of agouti. The material was washed with PBS solution and dissociated mechanically with the aid of a scalpel blade on plates containing culture medium D-MEM/F-12, and incubated at 5% CO2-37⁰C. The growth curve, CFU assay, osteogenic/adipogenic differentiation and characterization were obtained from the isolation. The cells began to be released from the explant tissue around the 7th day of culture. By day 22 of culture, cells reached 80% confluence. At the UFC test, 81 colonies were counted with 12 days of cultivation. The growth curves before and after freezing showed a regular growth with intense proliferation and clonogenic potential. The cell differentiation showed formation of osteoblasts and fat in culture, starting at 15 days of culture in a specific medium. Flow cytometry (FACs was as follows: CD34 (positive, CD14 (negative, CD45 (negative, CD73 (positive, CD79 (negative, CD90 (positive, CD105 (positive, demonstrating high specificity and commitment of isolated cells with mesenchymal stem cells strains. These results suggest the existence of a cell population of stem cells with mesenchymal features from the isolated tissue in the explants of agouti dental pulp, a potential model for study of stem cell strains obtained from the pulp tissue.

  20. Liquid and Frozen Storage of Agouti (Dasyprocta leporina) Semen Extended with UHT Milk, Unpasteurized Coconut Water, and Pasteurized Coconut Water.

    Science.gov (United States)

    Mollineau, W M; Adogwa, A O; Garcia, G W

    2010-09-14

    This study evaluated the effects of semen extension and storage on forward progressive motility % (FPM%) in agouti semen. Three extenders were used; sterilized whole cow's milk (UHT Milk), unpasteurized (CW) and pasteurized coconut water (PCW), and diluted to 50, 100, 150, and 200 × 10(6) spermatozoa/ml. Experiment 1: 200 ejaculates were extended for liquid storage at 5(∘)C and evaluated every day for 5 days to determine FPM% and its rate of deterioration. Experiment 2: 150 ejaculates were extended for storage as frozen pellets in liquid nitrogen at -195(∘)C, thawed at 30(∘) to 70(∘)C for 20 to 50 seconds after 5 days and evaluated for FPM% and its rate of deterioration. Samples treated with UHT milk and storage at concentrations of 100 × 10(6) spermatozoa/ml produced the highest means for FPM% and the slowest rates of deterioration during Experiment 1. During Experiment 2 samples thawed at 30(∘)C for 20 seconds exhibited the highest means for FPM% (12.18 ± 1.33%), 85% rate of deterioration. However, samples were incompletely thawed. This was attributed to the diameter of the frozen pellets which was 1 cm. It was concluded that the liquid storage method was better for short term storage.

  1. Morphology of the male agouti accessory genital glands (Dasyprocta prymnolopha Wagler, 1831 Morfologia das glândulas genitais acessórias em cutias (Dasyprocta prymnolopha Wagler, 1831

    Directory of Open Access Journals (Sweden)

    Danilo J. Ayres de Menezes

    2010-09-01

    Full Text Available The morphology of the accessory genital glands of the male agouti was studied in twenty-three animals that were raised in captivity. Twenty animals had their genital glands dissected in situ for macroscopic description. The samples of each gland were recovered, embedded in paraffin, sliced and stained by Hematoxylin-Eosin technique. It was founded four pairs of glands: the vesicular glands, the coagulating glands, the prostate and the bulbourethral glands. Histological characteristics of the vesicular, coagulating and prostate glands showed similar morphology, within the pseudostratified columnar epithelium. The tubulo-alveolar type of the bulbourethral glands showed a lack of connective tissue among the tubules, a small amount of red stained presented it the cytoplasm, and the presence of vacuoles in the tissue. This study concluded that the agouti showed to have similar morphological aspect described in the others species of rodents.A morfologia das glândulas genitais acessórias de cutias foram estudados em 23 animais criados em cativeiros. Vinte animais tiveram suas glândulas genitais dissecadas in situ para as descrições macroscópicas. Para o estudo microscópico foram utilizados três animais. Os fragmentos de cada glândula foram embebidos em parafina, seccionados e corados em hematoxilina e eosina. Foram encontrados quatro pares de glândulas: vesiculares, coaguladoras, próstata e bulbouretrais. As características histológicas da glândula vesicular, coaguladora e próstata mostraram morfologia similar, com epitélio colunar pseudoestratificado. O tipo tuboalveolar da glândula bulbouretral mostrou uma deficiência de tecido conjuntivo, citoplasma pouco corado e presença de vacúolos. Este estudo concluiu que a cutia apresenta as mesmas características morfológicas das glândulas genitais acessórias encontradas em roedores.

  2. Thoracic and heart biometrics of non-anesthetized agouti (Dasyprocta primnolopha Wagler, 1831 measured on radiographic images Biometria torácica e cardíaca de cutias não anestesiadas (Dasyprocta primnolopha Wagler, 1831 mensuradas em imagens radiográficas

    Directory of Open Access Journals (Sweden)

    Anaemilia das N. Diniz

    2013-03-01

    Full Text Available The agouti is a species intensively hunted throughout the Amazon and the semi-arid regions of northeastern Brazil. Considering the current trend in conservation management of wild species, the aim of this study was to determine the morphometric reference to the heart of agouti raised in captivity, based on thoracic and cardiac measurements in these animals. Thirty adult agoutis, 1 to 3 years of age, without clinical signs of cardiac disease were selected. The animals were physically restrained and radiographies in laterolateral (LL and ventrodorsal (VD recumbence were produced. The following measures were taken: the apicobasilar length of the heart (at the most cranial height of the Carina region to the heart apex (AB, maximum width of the heart perpendicular to AB (CD, heart inclination angle (AIC, trachea inclination angle (AIT, distance from the right heart wall (DPTd, distance from the left heart wall (DPTe and vertical depth of the thorax, and the ventral face of the vertebral column to the dorsal border of the sternum at the level of the trachea bifurcation (H. The ratios between AB/CD, AB/H and CD/H were also analyzed. To calculate the vertebral heart scale (VHS, the AB and CD measurements were laid over the thoracic vertebra starting at T4. Radiographic evaluation showed values consistent with those reported in small animals and some wild and exotic species. The main biometric values in the chest cavity and heart of agouti are arranged as follows: (1 The ratios between AB/H ratio and CD/H were not sensitive for identifying heart increases (p>0.05, while the ratio AB/CD was more sensitive in this identification (pA cutia é uma espécie intensamente caçada em toda a Amazônia e nas regiões semi-áridas do Nordeste do Brasil. Considerando a tendência atual em gestão de conservação das espécies selvagens, o objetivo deste estudo foi determinar referências morfométricas para o coração de cutia criadas em cativeiro, com base em

  3. Análise qualitativa do estabelecimento da espermatogênese em cutias (Dasyprocta aguti criadas em cativeiros

    Directory of Open Access Journals (Sweden)

    Antônio Chaves de Assis-Neto

    2003-01-01

    Full Text Available A determinação do estabelecimento da puberdade é bastante estudada em animais domésticos e roedores, no entanto, são escassas as pesquisas com a finalidade de estabelecer parâmetros para a biologia reprodutiva em cutias. Foram utilizadas 31 cutias machos da espécie Dasyprocta agouti, oriundas da Universidade Federal do Piauí, Estado do Piauí, e da Escola Superior de Agricultura de Mossoró, Estado do Rio Grande do Norte. Imediatamente após a orquiectomia foram retirados fragmentos e estes foram processados histologicamente, os tecidos foram corados com hematoxilina-eosina e analisou-se os parâmetros seguintes: aspectos de luminação dos túbulos seminíferos; presença de espermatócitos primários; presença de espermátides e formação dos primeiros estágios do ciclo do epitélio seminífero (CES segundo o método da morfologia tubular. O período desde o nascimento até os cinco meses de idade correspondeu à fase impúbere; dos seis aos oito meses de idade a fase de transição da pré-puberdade à puberdade; dos nove aos dez meses de idade à fase da puberdade; e dos doze aos quartoze meses de idade à fase da pós-puberdade. A puberdade da cutia (Dasyprocta aguti, ocorreu em animais a partir dos sete meses de idade, e o estabelecimento da puberdade foi constatado em todos os animais estudados aos nove meses de idade.

  4. Parasitism of two zoonotic reservoirs Dasyprocta leporina and D. fuliginosa (Rodentia from Amazonas, with Trichostrongylina nematodes (Heligmonellidae: description of a new genus and a new species

    Directory of Open Access Journals (Sweden)

    Alessandra Queiroga Gonçalves

    2007-09-01

    Full Text Available A new genus and a new species of Heligmonellidae nematodes are described parasiting the stomach of three agoutis (two Dasyprocta fuliginosa and one D. leporina captured in the middle and high Negro river microregion, state of Amazonas, Brazil. The new genus, as well as its type-species, are closely related to the trichostrongylids included in Fuellebornema, particularly on what concerns the pattern of the caudal bursa, but differing from them by the characteristics of the synlophe, that presents a poorly developed carene, when compared to the referred number of body ridges in Freitastrongylus n. gen. and consequently in F. angelae n. sp.,in which the ridges are well developed and the carene at mid-body has a similar size when compared to the ridge situated in front of the right field (ridge no. 5. Caudal bursa is of the type 1-4, with rays 9 shorter than rays 10, with a very long genital cone.

  5. Morfologia da laringe de cutia (Dasyprocta sp.

    Directory of Open Access Journals (Sweden)

    Andrezza B.S. Silva

    2014-06-01

    Full Text Available A cutia (Dasyprocta sp. é um roedor silvestre com distribuição mundial. Atualmente, além de importante papel ecológico que exerce, está sendo utilizada como modelo em experimento animal. Estudos sobre a morfologia destes animais são importantes porque podem ser uma alternativa para o estudo de diversos processos patológicos, além de contribuirem para a preservação da espécie. A laringe é um órgão localizado entre a faringe e a traqueia, no qual está envolvido nas funções de respiração, deglutição e fonação. O presente estudo propôs realizar uma descrição morfológica macroscópica e microscópica da laringe da cutia. Para tanto, foram utilizadas quinze cutias pertencentes ao Centro de Ciências Agrárias da Universidade Federal do Piauí e provenientes do Núcleo de Estudos e Preservação de Animais Silvestres com licença do IBAMA (Nº 02/08-618, CTF Nº 474064. Todos os animais foram identificados, promovida a sexagem e, posteriormente, a laringe acessada e dissecada sendo os fragmentos cartilagíneos encaminhados para rotina histológica e corados pelo método de hematoxilina-eosina. As lâminas obtidas foram visualizadas em microscopia óptica de luz e foto documentadas. A laringe da cutia apresenta cinco cartilagens, com ausência da cartilagem cuneiforme e presença da incisura caudal na cartilagem tireoide. O tecido epitelial da laringe varia de epitélio estratificado pavimentoso queratinizado à não queratinizado e ciliado com células caliciformes.

  6. The coronary arteries of the agouti (Agouti paca, Linnaeus, 1766

    Directory of Open Access Journals (Sweden)

    Fabrício Singaretti de Oliveira

    2009-12-01

    Full Text Available The present study aimed to describe the coronary arteries in the agouti. Twelve hearts set, in a 10% formaldehyde aqueous solution, were used. The presence of left and right coronary arteries was observed in all hearts. The fi rst arose from the aorta, between the left auricle and the pulmonary trunk, and gave off into a circumfl ex branch, whichever was directed to the right surface of this viscerae, and an interventricular paraconal branch that went through the cardiac apex, on the left atrioventricular sulcus. In 91.6% of the cases, at its origin, the paraconal branch gave off a thick side branch to the left ventricle wall, and in 100% of the cases, went deep, characterizing a large myocardial bridge. In 8.4% of the cases, this thick side branch to the left ventricle wall originated directly from the left coronary artery and not from the paraconal branch, and alterations such those to the circumfl ex branch did not occur. Regarding the right coronary artery, the origin of this vessel was from the aorta, on the atrial surface, in the direction of the right ventricular border, going through the subsinuous interventricular sulcus as an interventricular subsinuous branch.

  7. The organization of the brainstem nuclei associated with the vagus nerve in the Agouti (Dasyprocta leporina). A neurohistological study.

    Science.gov (United States)

    Phillips, C M; Odekunle, A

    2011-01-01

    A total of six adult animals were used for the study. Following anaesthesia via intraperitoneal injection of a mixture of ketamin and bombazine in ratio 2:1, thoracotomy was performed to exteriorize the heart for intracardial perfusion. The perfusion canular was inserted into the left ventricle and animal perfused sequentially with normal saline and 10% formal saline. Following perfusion, craniotomy was performed to remove the entire brain along with the upper segments of the spinal cord. The brain specimen was then dehydrated, cleared and infiltrated with paraffin wax. The specimen was then cut in 15 micron thick serial sections. The sections were then processed for neurohistological analyses using a Nikon microscope to which was attached Nikon camera. Analyses of the sections revealed bilateral representation of the dorsal motor nucleus of the vagus nerve in the medulla oblongata. The nucleus ambiguus, nucleus of the tractus solitarius, hypoglossal nucleus and the area postrema were also identified in the medulla oblongata. The implications of our findings are discussed in the text of the article.

  8. Genetic organization of the agouti region of the mouse

    Energy Technology Data Exchange (ETDEWEB)

    Siracusa, L.D.; Russell, L.B.; Eicher, E.M.; Corrow, D.J.; Copeland, N.G.; Jenkins, N.A.

    1987-09-01

    The agouti locus on mouse chromosome 2 acts via the hair follicle to control the melanic type and distribution of hair pigments. The diverse phenotypes associated with various agouti mutations have led to speculation about the organization of the agouti locus. Earlier studies indicated that two presumed agouti alleles, lethal yellow (A/sup y/) and lethal light-bellied nonagouti (a/sup x/), are pseudoallelic. The authors present genetic data showing probable recombination between A/sup y/ and three agouti mutations (a/sup t/, a, and a/sup x/), which suggest that A/sup y/ is a pseudoallele of the agouti locus. The close linkage of an endogenous ecotropic murine leukemia provirus, Emv-15, to A/sup y/ provides a molecular access to genes at or near the agouti locus. However, previous studies suggested that the Emv-15 locus can recombine with some agouti alleles and therefore they analyzed mice from recombinant inbred strains and backcrosses to measure the genetic distance between various agouti alleles and the Emv-15 locus. The data indicate that the Emv-15 locus is less the 0.3 cM from the agouti locus. These experiments provide a conceptual framework for initiating chromosome walking experiments designed to retrieve sequences from the agouti locus and give new insight into the genetic organization of the agouti region.

  9. Specialization of pyramidal cell structure in the visual areas V1, V2 and V3 of the South American rodent, Dasyprocta primnolopha.

    Science.gov (United States)

    Elston, Guy N; Elston, Alejandra; Freire, Marco Aurelio M; Gomes Leal, Wallace; Dias, Ivanira Amaral; Pereira, Antonio; Silveira, Luiz Carlos L; Picanço Diniz, Cristovam W

    2006-08-23

    Marked phenotypic variation has been reported in pyramidal cells in the primate cerebral cortex. These extent and systematic nature of these specializations suggest that they are important for specialized aspects of cortical processing. However, it remains unknown as to whether regional variations in the pyramidal cell phenotype are unique to primates or if they are widespread amongst mammalian species. In the present study we determined the receptive fields of neurons in striate and extrastriate visual cortex, and quantified pyramidal cell structure in these cortical regions, in the diurnal, large-brained, South American rodent Dasyprocta primnolopha. We found evidence for a first, second and third visual area (V1, V2 and V3, respectively) forming a lateral progression from the occipital pole to the temporal pole. Pyramidal cell structure became increasingly more complex through these areas, suggesting that regional specialization in pyramidal cell phenotype is not restricted to primates. However, cells in V1, V2 and V3 of the agouti were considerably more spinous than their counterparts in primates, suggesting different evolutionary and developmental influences may act on cortical microcircuitry in rodents and primates.

  10. Some remarks on the distribution and dispersion of Coccidia from icterid birds in South America: Isospora guaxi n. sp. and Isospora bellicosa Upton, Stamper & Whitaker, 1995 (Apicomplexa: Eimeriidae) from the red-rumped cacique Cacicus haemorrhous (L.) (Passeriformes: Icteridae) in southeastern Brazil.

    Science.gov (United States)

    da Silva, Lidiane Maria; Rodrigues, Mariana Borges; de Pinho, Irlane Faria; do Bomfim Lopes, Bruno; Luz, Hermes Ribeiro; Ferreira, Ildemar; Lopes, Carlos Wilson Gomes; Berto, Bruno Pereira

    2017-01-01

    A new species of coccidian, Isospora guaxi n. sp., and Isospora bellicosa Upton, Stamper & Whitaker, 1995 (Protozoa: Apicomplexa: Eimeriidae) are recorded from red-rumped caciques Cacicus haemorrhous (L.) in the Parque Nacional do Itatiaia, Brazil. Isospora guaxi n. sp. has sub-spheroidal oöcysts, measuring on average 30.9 × 29.0 μm, with smooth, bi-layered wall c.1.9 μm thick. Micropyle and oöcyst residuum are absent, but a polar granule is present. Sporocysts are ellipsoidal, measuring on average 19.3 × 13.8 μm. Stieda body is knob-like and sub-Stieda body is prominent and compartmentalized. Sporocyst residuum is composed of scattered granules. Sporozoites are vermiform, with one refractile body and a nucleus. Isospora bellicosa has sub-spheroidal to ovoidal oöcysts, measuring on average 27.1 × 25.0 μm, with smooth, bi-layered wall c.1.5 μm thick. Micropyle and oöcyst residuum are absent, but one or two polar granules are present. Sporocysts are ellipsoidal, measuring on average 18.1 × 10.9 μm. Stieda body is knob-like and sub-Stieda body is rounded to rectangular. Sporocyst residuum is composed of a cluster of compact or diffuse granules. Sporozoites are vermiform, with one refractile body and a nucleus. Isospora bellicosa was originally described from the Peruvian meadowlark Sturnella bellicosa deFilippi, a trans-Andean icterid which is allopatric with the cis-Andean C. haemorrhous. Therefore, in conclusion, this current study reveals the dispersion of coccidia from Icteridae across the Andes Mountains, besides describing the sixth isosporoid coccidium infecting an icterid bird.

  11. Melanocortin receptor binding determinants in the agouti protein.

    Science.gov (United States)

    Kiefer, L L; Veal, J M; Mountjoy, K G; Wilkison, W O

    1998-01-27

    The agouti protein plays an important role in the development of diabetes and obesity in rodents and has been shown to be a potent antagonist of melanocortin receptors. For this reason alanine-scanning mutagenesis was performed on the agouti protein carboxyl terminus to locate residues important for melanocortin receptor binding inhibition. When agouti residues Arg116 and Phe118 are changed to alanine, very large decreases in agouti affinity for melanocortin receptor 1, 3, and 4 result. Mutation of Phe117 to alanine causes a similar increase in agouti KI app at melanocortin receptor 4. Substitution of agouti residue Asp108 with alanine results in large increases in KI app for all three melanocortin receptors examined. All of these residues are conserved in the agouti-related transcript, ART, whose expression is up-regulated in animal models of obesity. The three-dimensional structure of the agouti carboxyl terminus was modeled, and residues which decrease receptor binding by a factor of > or = 15 when mutated to alanine localize to one side of the structure. These agouti variants with altered receptor selectivity may be useful in determining the role of melanocortin receptors in diabetes and obesity.

  12. INDICADORES HEMATOLÓGICOS Y HEMOQUÍMICOS DE Dasyprocta fuliginosa (GUARA, GUATÍN O ÑEQUE EN CAUTIVERIO

    Directory of Open Access Journals (Sweden)

    Lizcano L.

    2006-11-01

    Full Text Available Los indicadores hematológicos y hemoquímicos de la Dasyprocta fuliginosa (guara, guatín o ñeque en cautiverio se realizaron en el municipio de Florencia, Caquetá (Colombia, pretendiendo iniciar una referencia de datos para estudios de conservación, manejo productivo y clínico de la especie. Fueron utilizados diez animales machos en dos estados de desarrollo (juveniles y adultos. Para hemograma se determinaron hematocrito (técnica de microhematocrito, hemoglobina (método espectrofotométrico de la cianometahemoglobina, recuento total de leucocitos (técnica del hemocitómetro y recuento diferencial de leucocitos (frotis sanguíneo coloreado, y en hemoquímica se determinó glicemia (método GOD-PAP, colesterol (método CHOD-PAP, triglicéridos (método GPO-PAP, proteínas totales (método Biuret y creatinina (método colorimétrico simétrico. Los valores promedios para los parámetros evaluados en hemograma fueron: hematocrito 49,9 ± 2,9%; hemoglobina 16,5 ± 1,1 g/dl; recuento leucocitario total 6650 ± 1276,9 leucocitos/mm3; neutrófilos 17,7 ± 12,9%; linfocitos 77,6 ± 12,4%, y eosinófilos 5,1 ± 3,2 %. Para hemoquímica los resultados fueron: glicemia 249,9 ± 47,1 mg/dl; colesterol 108,1 ± 20,1 mg/dl; triglicéridos 108,1 ± 20,1 mg/dl, proteínas totales 5,7 ± 0,6 g/dl, y creatinina 1,7 ± 0,2 mg/dl. En algunos individuos los valores se desviaron significativamente del promedio, debiéndose tal vez a circunstancias fisiológicas e individuales (estrés, respuesta a mecanismos externos o por lesiones que padecían días antes a la toma de la muestra. Los indicadores del hemograma estuvieron en promedios similares a los de otros roedores del piedemonte amazónico: Proechimys sp., Agouti paca e Hydrochaeris hydrochaeris, al igual que en los hemoquímicos, salvo en glicemia, en donde se encontraron mayores valores para Dasyprocta fuliginosa, debido posiblemente al régimen alimenticio que se basaba sobre todo en frutas y

  13. INTESTINAL MICROBIOTE IN AGOUTIS BRED IN CAPTIVITY MICROBIOTA INTESTINAL EM CUTIAS CRIADAS EM CATIVEIRO

    Directory of Open Access Journals (Sweden)

    LEANDRO LUÍS MARTINS

    2009-07-01

    Full Text Available Intestines are colonized by microorganisms, which vary according to the species and the intestinal region. Thus, due the lack of information about this subject in literature, this research was developed for better knowing some aspects of the intestinal microbiology of the agouti, considered one of the biggest Brazilian wild rodents. Three males and three not pregnant adult females, belonging to the Catanduva City Zoo, SP, went through laparotomy after anesthesia. Samples were collected with sterile swab in the medium thirds of the jejune, cecum and greater colon after enterotomy. They were cultivated in Sabouraud agar and in TSA (triptone-soy agar. In the jejune, the growth of Staphylococcus aureus and Escherichia coli was of 83.33%, Salmonella spp. of 66.67% and Clostridium spp. of 50.00% of the samples. In the cecum, they were identified Staphylococcus aureus in 33.33%, Escherichia coli, Salmonella spp. and Clostridium spp. in 100% and Streptococcus spp. in 16.67% of the samples were identified. In the greater colon, the growth of Salmonella spp., Escherichia coli and Clostridium spp. in 66.67%, Staphylococcus aureus in 83.33%, and Streptococcus spp. in 16.67% of the samples was observed, showing the occurrence of variations in the bacteriae proportion according to the intestinal region. 

    KEY WORDS: Dasyprocta azarae, intestines, microbiote.

    Os intestinos são colonizados por microorganismos, variáveis de acordo com a espécie e região intestinal. Assim, em virtude da ausência de informações sobre esse assunto na literatura, esta pesquisa foi desenvolvida para melhor se conhecer alguns aspectos da microbiota intestinal da cutia, um dos maiores roedores selvagens brasileiros. Três machos e três fêmeas adultas vazias, pertencentes ao Zoológico Municipal de Catanduva, SP, foram submetidos a laparotomia mediante anestesia. Amostras com swab estéril foram coletadas nos terços médios do jejuno, ceco e c

  14. Mutations in the carboxyl terminus of the agouti protein decrease agouti inhibition of ligand binding to the melanocortin receptors.

    Science.gov (United States)

    Kiefer, L L; Ittoop, O R; Bunce, K; Truesdale, A T; Willard, D H; Nichols, J S; Blanchard, S G; Mountjoy, K; Chen, W J; Wilkison, W O

    1997-02-25

    Several mutations that cause ectopic expression of the agouti gene result in obesity, hyperinsulinemia, and yellow coat color. A candidate pathway for agouti induced obesity and hyperinsulinemia is through altered signaling by melanocortin receptors, as agouti normally regulates coat coloration through antagonism of melanocortin receptor 1. Furthermore, melanocortin peptides mediate functions including steroidogenesis, lipolysis, and thermoregulation. We report apparent inhibition dissociation constants for mouse and human agouti protein inhibition of ligand binding to the melanocortin receptors, to determine which of these receptors might be involved in agouti induced diabetes. The similarity in the apparent K(I) values for agouti inhibition of ligand binding to the brain melanocortin receptors 3 and 4 (mouse: K(I) app = 190 +/- 74 and 54 +/- 18 nM; human: K(I) app = 140 +/- 56 and 70 +/- 18 nM, respectively) suggests that the MC3-R is a potential candidate for a receptor mediating the effects of agouti protein overexpression. Agouti residues important for melanocortin receptor inhibition were identified through the analysis of deletion constructs and site-specific variants. Val83 is important for inhibition of binding to MC1-R (K(I) app for Val83Ala agouti increased 13-fold relative to wild-type protein). Arg85, Pro86, and Pro89 are important for selective inhibition of binding between MC1-R and MC3-R and MC4-R as their apparent K(I) values are essentially unchanged at MC1-R, while they have increased 6-10-fold relative to wild-type protein at MC3-R and MC4-R.

  15. AGOUTI: improving genome assembly and annotation using transcriptome data.

    Science.gov (United States)

    Zhang, Simo V; Zhuo, Luting; Hahn, Matthew W

    2016-07-19

    Genomes sequenced using short-read, next-generation sequencing technologies can have many errors and may be fragmented into thousands of small contigs. These incomplete and fragmented assemblies lead to errors in gene identification, such that single genes spread across multiple contigs are annotated as separate gene models. Such biases can confound inferences about the number and identity of genes within species, as well as gene gain and loss between species. We present AGOUTI (Annotated Genome Optimization Using Transcriptome Information), a tool that uses RNA sequencing data to simultaneously combine contigs into scaffolds and fragmented gene models into single models. We show that AGOUTI improves both the contiguity of genome assemblies and the accuracy of gene annotation, providing updated versions of each as output. Running AGOUTI on both simulated and real datasets, we show that it is highly accurate and that it achieves greater accuracy and contiguity when compared with other existing methods. AGOUTI is a powerful and effective scaffolder and, unlike most scaffolders, is expected to be more effective in larger genomes because of the commensurate increase in intron length. AGOUTI is able to scaffold thousands of contigs while simultaneously reducing the number of gene models by hundreds or thousands. The software is available free of charge under the MIT license.

  16. Nocturnal activity by the primarily diurnal Central American agouti (Dasyprocta punctata) in relation to environmental conditions, resource abundance and predation risk

    NARCIS (Netherlands)

    Lambert, T.D.; Kays, R.W.; Jansen, P.A.; Aliaga-Rosse, E.; Wikelski, M.

    2009-01-01

    An animal's fitness is in part based on its ability to manage the inherent risks (foraging costs, predation, exposure to disease) with the benefits (resource gain, access to mates, social interactions) of activity (Abrams 1991, Altizer et al. 2003, Lima & Bednekoff 1999, Rubenstein & Hohmann

  17. Analysis of the function of the agouti gene in obesity and diabetes

    Energy Technology Data Exchange (ETDEWEB)

    Mynatt, R.L.; Miltenberger, R.J.; Klebig, M.L. [and others

    1996-09-01

    This chapter discusses the agouti gene and dominant mutations in that gene that lead to agouti-induced obesity, and recent work with transgenic mice to elucidate the role of agouti in obesity. Agouti was cloned in 1992 by the lab of Rick Woychik at Oak Ridge National Laboratory, making it the first of many recently cloned mouse obesity genes. Sequence analysis predicted that mouse agouti is a secreted protein of 131 amino acids. The mature protein has a basic central region (lys57-arg85), a proline-rich domain (pro86-pro91) and a C-terminal region (cys 92-cys 13 1) containing 10 cysteine residues which form 5 disulfide bonds. The human homologue of agouti has also been cloned by the Woychik lab and maps to human chromosome 20q 11.2. Human agouti is 132 amino acids long and is 85% similar to the mouse agouti protein and is normally expressed in adipose tissue. The researchers have been able to recapitulate obesity, hyperinsulinemia, and hyperglycemia with the ubiquitous expression of agouti. Agouti expression in either liver and adipose tissue alone does not cause obesity, and there`s a dose-dependent effect of agouti on body weight, food efficiency, body temperature, and insulin and glucose levels.

  18. DESCRIÇÃO HISTOLÓGICA DOS INCISIVOS DA CUTIA Dasyprocta prymnolopha (Wagler, 1831

    Directory of Open Access Journals (Sweden)

    Weber Leal de Moura

    2006-10-01

    Full Text Available Esse trabalho objetivou descrever a histologia do dente e do periodonto de cutia. Utilizaram-se dez exemplares de Dasyprocta prymnolopha, desconsiderando idade e sexo. Realizado o processamento histológico clássico, o esmalte e o cemento desintegraram-se na descalcificação, evidenciando-se que o cemento apresenta uma quantidade de tecido mineralizado maior que a dentina. Na dentina, observaram-se túbulos dentinários, estriações paralelas, flexíveis, sinuosas e perpendiculares ao eixo maior do dente, presentes em maior quantidade na região próxima à pré-dentina. A dentina foi classificada em peritubular, intertubular e interglobular, além da pré-dentina, delgada porção não mineralizada. Os odontoblastos mostraram-se acidófilos, paralelos, dispostos ‘’em paliçada’’, ocupando o espaço entre a dentina e a polpa. A polpa apresentou tecido conjuntivo frouxo bastante vascularizado e inervado, cujas células predominantes foram fibroblastos de aspecto estrelado e fusiforme com longos prolongamentos citoplasmáticos. O periodonto mostrou cemento, ligamento periodontal e osso alveolar. O ligamento foi classificado em inferior (conjuntivo denso e superior (conjuntivo frouxo com o primeiro apresentando áreas globulares provenientes da comunicação do osso alveolar e o segundo um epitélio juncional pseudo-estratificado. As fibras de Sharpey partiam do ligamento, inserindo-se no osso alveolar,cujas lamelas formariam delgadas trabéculas e de osso compacto formado pelos sistemas de Havers. PALAVRAS-CHAVE: Dente, dentino-pulpar, Dasyprocta periodonto.

  19. Isolation and characterization of Agouti: a diabetes/obesity related gene

    Energy Technology Data Exchange (ETDEWEB)

    Woychik, Richard P. (Knoxville, TN)

    1998-01-01

    The present invention relates to the cloning and expression of the Agouti gene and analogous genes in transformed, transfected and transgenic mice. The present invention provides an animal model for the study of diabetes, obesity and tumors for the testing of potential therapeutic agents. The present invention provides oligonucleotide probes for the detection of the Agouti gene and mutations in the gene. The present invention also relates to the isolation and recombinant production of the Agouti gene product, production of antibodies to the Agouti gene product and their use as diagnostic and therapeutic agents.

  20. Isolation and characterization of Agouti: a diabetes/obesity related gene

    Energy Technology Data Exchange (ETDEWEB)

    Woychik, Richard P. (Knoxville, TN)

    2000-06-27

    The present invention relates to the cloning and expression of the Agouti gene and analogous genes in transformed, transfected and transgenic mice. The present invention provides an animal model for the study of diabetes, obesity and tumors for the testing of potential therapeutic agents. The present invention provides oligonucleotide probes for the detection of the Agouti gene and mutations in the gene. The present invention also relates to the isolation and recombinant production of the Agouti gene product, production of antibodies to the Agouti gene product and their use as diagnostic and therapeutic agents.

  1. Agouti yellow mutation increases adrenal response to ACTH in mice.

    Science.gov (United States)

    Bazhan, Nadezhda M; Shevchenko, Antonina Y; Karkaeva, Nelli R; Yakovleva, Tatyana V; Makarova, Elena N

    2004-08-01

    Agouti protein (AP) and agouti-related protein with a similar sequence and action are endogenous antagonists of melanocortin receptors, implicated in the control of the hypothalamo-pituitary-adrenal (HPA) axis. Dominant mutation of the agouti gene (agouti yellow (A(y))) in heterozygous A(y)/a mice leads to ectopic overexpression of AP and produces an obese phenotype. The existing data on the HPA function in A(y)/a-mice are equivocal; therefore, the present study aimed to assess HPA function in 3-month-old male C57Bl/6J mice of two agouti genotypes: A(y)/a (ectopic AP overexpression) and a/a (absence of AP). In order to evaluate the HPA function, activating (15-min restriction, ACTH-induced corticosterone production in vitro) and inhibiting (i.p. injection of dexamethasone, 0.02 microg/g body weight) stimuli were employed. To estimate the effect of obesity on some HPA functions, A(y)/a males were subdivided into obese and non-obese groups. Basal plasma concentrations of ACTH and corticosterone; basal corticosterone production in vitro; and feedback inhibition of resting corticosterone levels by dexamethasone were similar in A(y)/a- and a/a-mice. Restraint-induced plasma corticosterone was greater in obese and non-obese A(y)/a-mice than in a/a-mice, whereas restraint-induced plasma ACTH levels were similar. Adrenal cell responses to ACTH (10(-13)-10(-10) M) were higher in obese and non-obese A(y)/a-mice than in a/a-mice. Dexamethasone, injected 3 h prior to stress, inhibited stress-induced corticosterone levels by a significantly greater amount in A(y)/a-mice than in a/a-mice. AP may have both stimulating and inhibiting influences on the HPA axis. AP overproduction increased the response of the HPA to short-restraint stress due to increased adrenal responsiveness to ACTH; this result was not effected by obesity development.

  2. Overexpression of agouti protein and stress responsiveness in mice.

    Science.gov (United States)

    Harris, R B; Zhou, J; Shi, M; Redmann, S; Mynatt, R L; Ryan, D H

    2001-07-01

    Ectopic overexpression of agouti protein, an endogenous antagonist of melanocortin receptors' linked to the beta-actin promoter (BAPa) in mice, produces a phenotype of yellow coat color, Type II diabetes, obesity and increased somatic growth. Spontaneous overexpression of agouti increases stress-induced weight loss. In these experiments, other aspects of stress responsiveness were tested in 12-week-old male wild-type mice and BAPa mice. Two hours of restraint on three consecutive days produced greater increases in corticosterone and post-stress weight loss in BAPa than wild-type mice. In Experiment 2, anxiety-type behavior was measured immediately after 12 min of restraint. This mild stress did not produce many changes indicative of anxiety, but BAPa mice spent more time in the dark side of a light-dark box and less time in the open arms of an elevated plus maze than restrained wild-type mice. In a defensive withdrawal test, grooming was increased by restraint in all mice, but the duration of each event was substantially shorter in BAPa mice, possibly due to direct antagonism of the MC4-R by agouti protein. Thus, BAPa mice showed exaggerated endocrine and energetic responses to restraint stress with small differences in anxiety-type behavior compared with wild-type mice. These results are consistent with observations in other transgenic mice in which the melanocortin system is disrupted, but contrast with reports that acute blockade of central melanocortin receptors inhibits stress-induced hypophagia. Thus, the increased stress responsiveness in BAPa mice may be a developmental compensation for chronic inhibition of melanocortin receptors.

  3. Interaction of Agouti protein with the melanocortin 1 receptor in vitro and in vivo

    Science.gov (United States)

    Ollmann, Michael M.; Lamoreux, M. Lynn; Wilson, Brent D.; Barsh, Gregory S.

    1998-01-01

    Agouti protein and Agouti-related protein (Agrp) are paracrine-signaling molecules that normally regulate pigmentation and body weight, respectively. These proteins antagonize the effects of α-melanocyte-stimulating hormone (α-MSH) and other melanocortins, and several alternatives have been proposed to explain their biochemical mechanisms of action. We have used a sensitive bioassay based on Xenopus melanophores to characterize pharmacologic properties of recombinant Agouti protein, and have directly measured its cell-surface binding to mammalian cells by use of an epitope-tagged form (HA–Agouti) that retains biologic activity. In melanophores, Agouti protein has no effect in the absence of α-MSH, but its action cannot be explained solely by inhibition of α-MSH binding. In 293T cells, expression of the Mc1r confers a specific, high-affinity binding site for HA-Agouti. Binding is inhibited by α-MSH, or by Agrp, which indicates that α-MSH and Agouti protein bind in a mutually exclusive way to the Mc1r, and that the similarity between Agouti protein and Agrp includes their binding sites. The effects of Agouti and the Mc1r in vivo have been examined in a sensitized background provided by the chinchilla (Tyrc-ch) mutation, which uncovers a phenotypic difference between overexpression of Agouti in lethal yellow (Ay/a) mice and loss of Mc1r function in recessive yellow (Mc1re/Mc1re) mice. Double and triple mutant studies indicate that a functional Mc1r is required for the pigmentary effects of Agouti, and suggest that Agouti protein can act as an agonist of the Mc1r in a way that differs from α-MSH stimulation. These results resolve questions regarding the biochemical mechanism of Agouti protein action, and provide evidence of a novel signaling mechanism whereby α-MSH and Agouti protein or Agrp function as independent ligands that inhibit each other’s binding and transduce opposite signals through a single receptor. PMID:9450927

  4. Cariotipo Citogenético de la Guagua (agouti paca

    Directory of Open Access Journals (Sweden)

    López Ortiz Juan Bautista

    1997-12-01

    Full Text Available El presente trabajo reporta la dotación cromosómica de Agouti paca, una especie considerada en vía de extinción. Además, se muestra la estandarización de la técnica para la obtención de cromosomas en sangre periférica y el tiempo óptimo del pulso terminal de 5-bromo-2 'deoxiuridina (BrdUrd para la obtención de bandas R-replicativas de alta resolución. También, se compara el cariotipo obtenido usando tinción convencional de Giemsa, con el realizado utilizando bandeo replicativo de alta resolución. El análisis de la morfología cromosómica del cariotipo de Agouti paca, muestra 29 pares de cromosomas subtelocéntricos, 2 cromosomas acrocéntricos y 5 pares cromosómicos metacéntricos. De todo el cariotipo, el cromosoma X es el más grande y lo clasificamos como: submetacéntrico. El cromosoma Y es el más pequeño y lo consideramos acrocéntrico. Además, al igual que en todas las hembras de mamíferos, la hembra de guagua exhibe un cromosoma X inactivo de replicación tardía. Con base en los resultados obtenidos, se determina el número cromosómico 2n = 74. De acuerdo con la ISCI (1995, propusimos una clasificación en 5 grupos: grupo A del 1 al 10, grupo B del 11 al 20, grupo C del 21 al 29, grupo D del 30 al 31 y grupo E del 32 al 36, además del parsexual (XX si es hembra, XY si es macho. Estos hallazgos posibilitarán en el futuro, establecer la correlación entre anormalidades cromosómicas y cambios fenotípicos o trastornos reproductivos de la especie; además, servirá como parámetro citogenético en la comparación de Agouti paca con otros Hystricomorfos relacionados. Este resultado se constituye en el primer cariotipo de Agouti paca (guagua, reportado; además, es el primer estudio citogenético donde se realizan bandas R-replicativas de alta resolución para cariotipar especies animales promisorias

  5. Molecular analysis of the mouse agouti gene and the role of dominant agouti-locus mutations in obesity and insulin resistance

    Energy Technology Data Exchange (ETDEWEB)

    Klebig, M.L.; Woychik, R.P. [Oak Ridge National Lab., TN (United States); Wilkinson, J.E. [Univ. of Tennessee, Knoxville, TN (United States)

    1994-09-01

    The lethal yellow (A{sup y/-}) and viable yellow (A{sup vy/-}) mouse agouti mutants have a predominantly yellow pelage and display a complex syndrome that includes obesity, hyperinsulinemia, and insulin resistance, hallmark features of obesity-associated noninsulin-dependent diabetes mellitus (NIDDM) in humans. A new dominant agouti allele, A{sup iapy}, has recently been identified; like the A{sup vy} allele, it is homozygous viable and confers obesity and yellow fur in heterozygotes. The agouti gene was cloned and characterized at the molecular level. The gene is expressed in the skin during hair growth and is predicted to encode a 131 amino acid protein, that is likely to be a secreted factor. In both Ay/- and A{sup iapy}/- mice, the obesity and other dominant pleiotropic effects are associated with an ectopic expression of agouti in many tissues where the gene product is normally not produced. In Ay, a 170-kb deletion has occurred that causes an upstream promoter to drive the ectopic expression of the wild-type agouti coding exons. In A{sup iapy}, the coding region of the gene is expressed from a cryptic promoter within the LTR of an intracisternal A-particle (IAP), which has integrated within the region just upstream of the first agouti coding exon. Transgenic mice ubiquitously expressing the cloned agouti gene under the influence of the beta-actin and phosphoglycerate kinase promoters display obesity, hyperinsulinemia, and yellow coat color. This demonstrates unequivocally that ectopic expression of agouti is responsible for the yellow obese syndrome.

  6. The agouti gene product inhibits lipolysis in human adipocytes via a Ca2+-dependent mechanism.

    Science.gov (United States)

    Xue, B; Moustaid-N; Wilkison, W O; Zemel, M B

    1998-10-01

    Overexpression of the murine agouti gene results in obesity. The human homologue of agouti is expressed primarily in human adipocytes, and we have shown recombinant agouti protein to increase adipocyte intracellular Ca2+([Ca2+]i) and thereby stimulate lipogenesis. However, since recent data demonstrate that increasing adipocyte [Ca2+]i may also inhibit lipolysis, we have investigated the role of agouti-induced [Ca2+]i increases in regulating lipolysis in human adipocytes. Short-term (1 h) exposure to recombinant agouti (100 nM) protein had no effect on basal lipolysis, although longer term treatment (24 h) caused a 60% decrease in basal lipolysis (Pagouti treatment totally inhibited ACTH-induced lipolysis (Pagouti, we next determined whether agouti's antilipolytic effect is exerted through competitive antagonism of the ACTH receptor (MCR-2). Forskolin (1 microM), an adenylate cyclase activator, induced a 48% increase in lipolysis in human adipocytes (Pagouti (Pagouti is distal to the ACTH receptor. To determine the role of [Ca2+]i in the antilipolytic effect of agouti, human adipocytes were treated with KCl or arginine vasopressin to stimulate voltage- and receptor-stimulated Ca2+ influx, respectively. Both agents caused inhibition of forskolin-induced lipolysis (Pagouti's antilipolytic effect was also blocked by the Ca2+ channel blocker nitrendipine. These data demonstrate that agouti exerts a potent antilipolytic effect in human adipocytes via a Ca2+-dependent mechanism. This effect, combined with agouti-induced lipogenesis, represents a coordinate control of adipocyte lipid metabolism that may contribute to an agouti-induced obesity syndrome.

  7. Leptin responsiveness in mice that ectopically express agouti protein.

    Science.gov (United States)

    Harris, Ruth B S; Mitchell, Tiffany D; Mynatt, Randall L

    Agouti protein is an endogenous antagonist of melanocortin receptors (MCR), including MCR3 and MCR4, which have been implicated as part of the hypothalamic mechanism that mediates leptin-induced hypophagia. In this experiment we examined the effects of peripheral and central leptin administration in male and female beta-actin promoter (BAPa) mice that express agouti protein ectopically and have a phenotype that includes obesity and diabetes which is exaggerated in males compared with females. Intraperitoneal infusion of 10 microg leptin/day for 13 days caused weight loss and a transient inhibition of food intake in wild-type mice, with a greater effect in males than females. Male BAPa mice were resistant to leptin infusion whereas female mice lost weight. All of the mice lost body weight following a single intracerebroventricular injection of leptin but the effect was greater in female BAPa mice than any other group. There also was a delayed suppression of food intake that was the same for wild-type and BAPa female mice, whereas food intake recovered faster in BAPa than wild-type males. The dissociation between food intake and body weight loss implies a significant effect of leptin on energy expenditure in BAPa mice. These results demonstrate that the effect of leptin on energy balance is not entirely dependent upon the melanocortin system.

  8. Agouti protein is an antagonist of the melanocyte-stimulating-hormone receptor.

    Science.gov (United States)

    Lu, D; Willard, D; Patel, I R; Kadwell, S; Overton, L; Kost, T; Luther, M; Chen, W; Woychik, R P; Wilkison, W O

    1994-10-27

    The genetic loci agouti and extension control the relative amounts of eumelanin (brown-black) and phaeomelanin (yellow-red) pigments in mammals: extension encodes the receptor for melanocyte-stimulating hormone (MSH) and agouti encodes a novel 131-amino-acid protein containing a signal sequence. Agouti, which is produced in the hair follicle, acts on follicular melanocytes to inhibit alpha-MSH-induced eumelanin production, resulting in the subterminal band of phaeomelanin often visible in mammalian fur. Here we use partially purified agouti protein to demonstrate that agouti is a high-affinity antagonist of the MSH receptor and blocks alpha-MSH stimulation of adenylyl cyclase, the effector through which alpha-MSH induces eumelanin synthesis. Agouti was also found to be an antagonist of the melanocortin-4 receptor, a related MSH-binding receptor. Consequently, the obesity caused by ectopic expression of agouti in the lethal yellow (Ay) mouse may be due to the inhibition of melanocortin receptor(s) outside the hair follicle.

  9. Role of melanocortinergic neurons in feeding and the agouti obesity syndrome.

    Science.gov (United States)

    Fan, W; Boston, B A; Kesterson, R A; Hruby, V J; Cone, R D

    1997-01-09

    Dominant alleles at the agouti locus (A) cause an obesity syndrome in the mouse, as a consequence of ectopic expression of the agouti peptide. This peptide, normally only found in the skin, is a high-affinity antagonist of the melanocyte-stimulating hormone receptor (MC1-R), thus explaining the inhibitory effect of agouti on eumelanin pigment synthesis. The agouti peptide is also an antagonist of the hypothalamic melanocortin-4 receptor (MC4-R). To test the hypothesis that agouti causes obesity by antagonism of hypothalamic melanocortin receptors, we identified cyclic melanocortin analogues that are potent agonists or antagonists of the neural MC3 (refs 11, 12) and MC4 receptors. Intracerebroventricular administration of the agonist, MTII, inhibited feeding in four models of hyperphagia: fasted C57BL/6J, ob/ob, and A(Y) mice, and mice injected with neuropeptide Y. Co-administration of the specific melanocortin antagonist and agouti-mimetic SHU9119 completely blocked this inhibition. Furthermore, administration of SHU9119 significantly enhanced nocturnal feeding, or feeding stimulated by a prior fast. Our data show that melanocortinergic neurons exert a tonic inhibition of feeding behaviour. Chronic disruption of this inhibitory signal is a likely explanation of the agouti obesity syndrome.

  10. Monitoramento do ciclo estral de cutias (Dasyprocta leporina Lichtenstein, 1823 através de citologia esfoliativa vaginal e ultrassonografia

    Directory of Open Access Journals (Sweden)

    Lívia B. Campos

    2015-02-01

    Full Text Available O objetivo deste estudo foi monitorar o ciclo estral em cutias (Dasyprocta leporina criadas em cativeiro no semiárido brasileiro. Durante 70 dias, cinco cutias foram diariamente submetidas a citologia esfoliativa vaginal, e o monitoramento ultrassonográfico ovariano foi realizado a cada três dias. Um total de 8 ciclos estrais foi completamente monitorado, com duração de 28,2±0,7 dias, variando de 24 a 31 dias. Pela citologia esfoliativa vaginal, houve uma predominância de células superficiais nas fases de proestro e estro (P0,05. Os folículos foram identificados durante as fases estrogênicas (proestro e estro, com diâmetro médio de 1±0,5mm. Em apenas 12,5% das fases luteais, corpos lúteos medindo 1,4±0,9mm foram identificados. Conclui-se que a associação da citologia vaginal e da ultrassonografia ovariana constitui uma alternativa viável para o monitoramento de ciclos estrais e identificação das fases estrogênicas em cutias da espécie Dasyprocta leporina

  11. Agouti regulation of intracellular calcium: Role in the insulin resistance of viable yellow mice

    Energy Technology Data Exchange (ETDEWEB)

    Zemel, M.B.; Kim, J.H. [Univ. of Tennessee, Knoxville, TN (United States); Woychik, R.P.; Michaud, E.J. [Oak Ridge National Laboratory, Oak Ridge, TN (United States); Hadwell, S.H.; Patel, I.R.; Wilkison, W.O. [Research Institute, Research Triangle Park, NC (United States)

    1995-05-23

    Several dominant mutations at the agouti locus in the mouse cause a syndrome of marked obesity, hyperinsulinemia, and insulin resistance. Although it is known that the agouti gene is expressed in an ectopic manner in these mutants, the precise mechanism by which the agouti gene product mediates these effects is unclear. Since intracellular Ca{sup 2+} is believed to play a role in mediating insulin action and dysregulation of Ca{sup 2+} flux is observed in diabetic animals and humans, we examined the status of intracellular Ca{sup 2+} in mice carrying the dominant agouti allele, viable yellow (A{sup vy}). We show here that in mice carrying this mutation, the intracellular free calcium concentration ([Ca{sup 2+}]{sub i}) is elevated in skeletal muscle, and the degree of elevation is closely correlated with the degree to which the mutant traits are expressed in individual animals. Moreover, we demonstrate that the agouti gene product is capable of inducing increased [Ca{sup 2+}]{sub i} in cultured and freshly isolated skeletal muscle myocytes from wild-type mice. Based on these findings, we present a model in which we propose that the agouti polypeptide promotes insulin resistance in mutant animals through its ability to increase [Ca{sup 2+}]{sub i}. 36 refs., 3 figs., 2 tabs.

  12. Agouti antagonism of melanocortin binding and action in the B16F10 murine melanoma cell line.

    Science.gov (United States)

    Blanchard, S G; Harris, C O; Ittoop, O R; Nichols, J S; Parks, D J; Truesdale, A T; Wilkison, W O

    1995-08-22

    Several dominant mutations at the murine agouti locus result in the expression of a number of phenotypic changes, including a predominantly yellow coat color, obesity, and hyperinsulinemia. The mutants exhibit ectopic overexpression of normal agouti protein, suggesting that agouti regulates coat coloration by direct antagonism of the alpha-melanocyte-stimulating hormone receptor. We have tested this hypothesis by examining agouti inhibition of both melanocortin-stimulated cyclic adenosine monophosphate production and the binding of a radioactive melanocortin analog in the murine B16F10 melanoma cell line. Inhibition of melanocortin-induced cyclic nucleotide accumulation did not require preincubation of the cells with agouti and was independent of the agonist used. Furthermore, inhibition of both agonist binding to and activation of melanocortin receptor could be described by a simple competitive model with similar inhibition constants of 1.9 and 0.9 nM, respectively. The mutually exclusive binding of agouti and melanocortin was verified by cross-linking experiments using a radiolabeled alpha-melanocyte-stimulating hormone analog. Competitive inhibition of alpha-melanocyte-stimulating hormone binding can account for the effects of agouti on coat coloration and suggests the possibility that the other phenotypic changes observed on agouti overexpression may be due to direct action of agouti at a novel melanocortin receptor(s).

  13. [Ovarian activity of Agouti paca (Rodentia: Agoutidae) under captivity].

    Science.gov (United States)

    Montes Pérez, Rubén C; Cabrera Baz, Elsy A

    2006-09-01

    The ovarian activity of Agouti paca was characterized by hormonal profiles and ovarian structures. Samples of blood were taken from eight females (seven adults and one juvenile) at the breeding grounds of the Facultad de Medicina Veterinaria y Zootecnia in Yucatśn, Mexico. Sampling lasted approximately two months and was done every three and six days. Blood was collected from anesthetized animals, and the levels of progesterone (P4) and 17 beta estradiol (E2) were analized by radioimmunoassay technique. Macroscopic and microscopic analyses were carried out in ovaries of dead animals. The estrous cycle lasted 29+/-8.4 days, levels of 1.61+/-0.65 ng/ml for P4 and 39+/-24 pg/ml for E2 were observed for a follicular phase, 6.18+/-3.70 ng/ml and 29+/-16 pg/ml for P4 and E2 respectively in the luteal phase. Statistically significant differences were found between phases for P4 but not for E2. The presence of extragonadal steroids with levels of P4 of 1.9+/-0.77 ng/ml and E2 of 22+/-17 pg/ml were observed, which are not produced by the effects of managing stress. The changes in the levels of P4 during the cycle are indicators of luteal activity, with the intersticial tissue acting probably as active steroids-producing gland. Follicular growth was observed during the entire cycle.

  14. Colheita de sêmen por eletroejaculação em cutia-parda (Dasyprocta azarae

    Directory of Open Access Journals (Sweden)

    Antonio C. Martinez

    2013-01-01

    Full Text Available As cutias são animais que vivem nas Américas Central e do Sul, com potencial zootécnico e que despertam crescente interesse científico. O objetivo deste estudo foi estabelecer um padrão para colheita de sêmen por eletroejaculação em cutia-parda (Dasyprocta azarae. Foram utilizados machos adultos (n=4 anestesiados e submetidos a quatro séries de 20 estímulos eletroejaculatórios, com 3 segundos de duração cada, com uma intensidade de 2, 4, 6 e 8 volts, com dois minutos de intervalo entre cada série. A colheita de sêmen foi obtida em todos os animais, com ereção parcial com 2 volts, ereção evidente com 4 volts, ejaculação com 6 volts e exacerbação da glande e exteriorização das espículas penianas com 8 volts, observando-se espermatozoides em 100% das amostras. A técnica descrita para colheita de sêmen em cutia-parda foi eficaz.

  15. Caracterización citogenética del tinajo o borugo Agouti taczanowskii de Colombia

    Directory of Open Access Journals (Sweden)

    Torres Olga María

    2000-12-01

    Full Text Available We describe the cytogenetics of the mountain paca, A. teczenowskii, which inhabits the mountains of Colombia. It was established that A. taczanowskií has a diploid number of 78 chromosomes with fairly large amounts of constitutive heterochromatin and remarkable C-band polymorphism. These results permit the differentiation of individuals and may shed light on the family status of the genus Agouti.Este trabajo presenta los cariotipos G, R Y C del tinajo o borugo A. taczanowskii que habita en los Andes de Colombia. A. taczanowskií posee 78 cromosomas, con una cantidad relativamente grande de heterocromatina constitutiva y un notable polimorfismo de bandas C, que permitió la identificación individual de los animales estudiados. Los resultados encontrados constituyen un punto de referencia importante para la taxonomía del género Agouti.

  16. Teriflunomide Attenuates Immunopathological Changes in the Dark Agouti Rat Model of Experimental Autoimmune Encephalomyelitis

    OpenAIRE

    Ringheim, Garth E.; Lan eLee; Lynn eLaws-Ricker; Thomas eDelohery; Li eLiu; Donghui eZhang; Nicholas eColletti; Soos, Timothy J.; Kendra eSchroeder; Barbara eFanelli; Nian eTian; Arendt, Christopher W; Deborah eIglesias-Bregna; Margaret ePetty; Zhongqi eJi

    2013-01-01

    Teriflunomide is an oral disease-modifying therapy recently approved in several locations for relapsing-remitting multiple sclerosis. To gain insight into the effects of teriflunomide, immunocyte population changes were measured during progression of experimental autoimmune encephalomyelitis in Dark Agouti rats. Treatment with teriflunomide attenuated levels of spinal cord-infiltrating T cells, natural killer cells, macrophages, and neutrophils. Teriflunomide also mitigated the disease-induce...

  17. The effects of calcium channel blockade on agouti-induced obesity

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jung Han; Moustaid, N.; Zemel, M.B. [Univ. of Tennessee, Knoxville, TN (United States)] [and others

    1996-12-01

    We have previously observed that obese viable yellow (A{sup vy}/a) mice exhibit increased intracellular Ca{sup 2+} ([Ca{sup 2+}]i) and fatty acid synthase (FAS) gene expression; further, recombinant agouti protein increases in cultured adipocytes and these effects are inhibited by Ca{sup 2+} channel blockade. Accordingly, we determined the effect of Ca{sup 2+} channel blockade (nifedipine for 4 wk) on FAS and obesity in transgenic mice expressing the agouti gene in a ubiquitous manner. The transgenic mice initially were significantly heavier (30.5 {+-} 0.6 vs. 27.3 {+-} 0.3 g; P<0.001) and exhibited a 0.81{degrees}C lower initial core temperature (P<0.0005), an approximately twofold increase in fat pad weights (P=0.002), a sevenfold increase in adipose FAS activity (P=0.009), and a twofold increase in plasma insulin level (P<0.05) compared to control mice. Nifedipine treatment resulted in an 18% decrease in fat pad weights (P<0.007) and a 74% decrease in adipose FAS activity (P=0.03), normalized circulating insulin levels and insulin sensitivity (P,0.05), and transiently elevated core temperature in the transgenic mice, but was without effect in the control mice. These data suggest that agouti regulates FAS, fat storage, and possibly thermogenesis, at least partially, via a [Ca{sup 2+}]{sub i}-dependent mechanism, and that Ca{sup 2+} channel blockade may partially attenuate agouti-induced obesity. 42 refs., 4 figs., 1 tab.

  18. Characterization of the dog agouti gene and a nonagouti mutation in german shepherd dogs

    Energy Technology Data Exchange (ETDEWEB)

    Kerns, Julie A.; Newton, J.; Berryere, Tom G.; Rubin, Edward M.; Cheng, Jan-Fang; Schmutz, Sheila M.; Barsh, Gregory S.

    2004-07-08

    The interaction between two genes, Agouti and Melanocortin-1 receptor (Mc1r), produces diverse pigment patterns in mammals by regulating the type, amount, and distribution pattern of the two pigment types found in mammalian hair: eumelanin (brown/black) and pheomelanin (yellow/red). In domestic dogs (Canis familiaris), there is a tremendous variation in coat color patterns between and within breeds; however, previous studies suggest that the molecular genetics of pigment-type switching in dogs may differ from that of other mammals. Here we report the identification and characterization of the Agouti gene from domestic dogs, predicted to encode a 131-amino-acid secreted protein 98 percent identical to the fox homolog, and which maps to chromosome CFA24 in a region of conserved linkage. Comparative analysis of the Doberman Pinscher Agouti cDNA, the fox cDNA, and 180 kb of Doberman Pinscher genomic DNA suggests that, as with laboratory mice, different pigment-type-switching patterns in the canine family are controlled by alternative usage of different promoters and untranslated first exons. A small survey of Labrador Retrievers, Greyhounds, Australian Shepherds, and German Shepherd Dogs did not uncover any polymorphisms, but we identified a single nucleotide variant in black German Shepherd Dogs predicted to cause an Arg-to-Cys substitution at codon 96, which is likely to account for recessive inheritance of a uniform black coat.

  19. Topografia, morfologia externa e distribuição arterial do baço em cutias (Dasyprocta prymnolopha

    Directory of Open Access Journals (Sweden)

    Maria Acelina Martins de Carvalho

    2017-05-01

    Full Text Available Esta pesquisa teve por objetivo avaliar a topografia e morfologia externa, ramificação e distribuição intraparenquimal dos vasos arteriais lienais do baço de cutia (Dasyprocta prymnolopha. Foram analisados vinte baços de animais jovens e adultos, treze machos e sete fêmeas, procedentes do Núcleo de Estudos e Preservação de Animais Silvestres do Centro de Ciências Agrárias da UFPI. Em dezesseis baços, verificou-se “in situ” a topografia e a morfologia externa, após a abertura da cavidade abdominal. Para o estudo da vascularização arterial, foram utilizados dez órgãos, destes, seis foram retirados da cavidade abdominal, injetados com Neoprene látex a 60%, por meio da artéria lienal, fixados com solução aquosa de formaldeído a 10%, e dissecados. Em outros quatro baços, procederam a repleção da referida artéria, com solução de acetato de vinil corado, submetidos ao método de corrosão, utilizando-se ácido sulfúrico a 30%, obtendo-se os moldes vasculares. Verificou-se o baço da cutia com formato triangular em 68,7%, e em 31,3%, retangular. A artéria lienal, sempre com divisão extra-parenquimal origina de 5 a 12 ramos, preponderantemente, 6 ramos, em 40% dos casos, que penetram no parênquima, vascularizam territórios independentes, caracterizando os segmentos arteriais. Em 20% dos baços examinados, observou-se artérias extra-hilares e, em apenas 1 caso (10% foi visto uma anastomose entre os ramos arteriais segmentares.

  20. Ectopic expression of the agouti gene in transgenic mice causes obesity, features of type II diabetes, and yellow fur

    Energy Technology Data Exchange (ETDEWEB)

    Klebig, M.L.; Woychik, R.P. [Oak Ridge National Laboratory, Oak Ridge, TN (United States); Wilkinson, J.E. [Univ. of Tennessee, Knoxville, TN (United States); Geisler, J.G. [Oak Ridge National Laboratory, Oak Ridge, TN (United States)]|[Univ. of Tennessee, Knoxville, TN (United States)

    1995-05-23

    Mice that carry the lethal yellow (A{sup y}) or viable yellow (A{sup vy}) mutation, two dominant mutations of the agouti (a) gene in mouse chromosome 2, exhibit a phenotype that includes yellow fur, marked obesity, a form of type II diabetes associated with insulin resistance, and an increased susceptibility to tumor development. Molecular analyses of these and several other dominant {open_quotes}obese yellow{close_quotes} a-locus mutations suggested that ectopic expression of the normal agouti protein gives rise to this complex pleiotropic phenotype. We have now tested this hypothesis directly by generating transgenic mice that ectopically express an agouti cDNA clone encoding the normal agouti protein in all tissues examined. Transgenic mice of both sexes have yellow fur, become obese, and develop hyperinsulinemia. In addition, male transgenic mice develop hyperglycemia by 12-20 weeks of age. These results demonstrate conclusively that the ectopic agouti expression is responsible for most, if not all, of the phenotypic traits of the dominant, obese yellow mutants. 42 refs., 5 figs.

  1. Maternal epigenetics and methyl supplements affect agouti gene expression in A{sup vy}/a mice

    Energy Technology Data Exchange (ETDEWEB)

    Wolff, G.L. [National Center for Toxicological Research/Food and Drug Administration, Jefferson, AR (United States)]|[Univ. of Arkansas for Medical Sciences, Little Rock, AR (United States); Kodell, R.L.; Cooney, C.A. [National Center for Toxicological Research/Food and Drug Administration, Jefferson, AR (United States); Moore, S.R. [Bionetics Corp., Jefferson, AR (United States)

    1998-08-01

    Viable yellow (A{sup vy}/a) mice are larger, obese, hyperinsulinemic, more susceptible to cancer, and, on average, shorter lived than their non-yellow siblings. They are epigenetic mosaics ranging from a yellow phenotype with maximum ectopic agouti overexpression, through a continuum of mottled agouti/yellow phenotypes with partial agouti overexpression, to a pseudoagouti phenotype with minimal ectopic expression. Pseudoagouti A{sup vy}/a mice are lean, healthy, and longer lived than their yellow siblings. Here the authors report that feeding pregnant black a/a dams methyl-supplemented diets alters epigenetic regulation of agouti expression in their offspring, as indicated by increased agouti/black mottling in the direction of the pseudoagouti phenotype. They also present confirmatory evidence that epigenetic phenotypes are maternally heritable. Thus A{sup vy} expression, already known to be modulated by imprinting, strain-specific modification, and maternal epigenetic inheritance, is also modulated by maternal diet. These observations suggest, at least in this special case, that maternal dietary supplementation may positively affect health and longevity of the offspring. Therefore, this experimental system should be useful for identifying maternal factors that modulate epigenetic mechanisms, especially DNA methylation, in developing embryos.

  2. Características reprodutivas da paca fêmea (Agouti paca criada em cativeiro Reprodutive characteristics of the female paca (Agouti paca raised in captivity

    Directory of Open Access Journals (Sweden)

    Diva Anelie de Araújo Guimarães

    2008-01-01

    Full Text Available O objetivo do trabalho foi estudar a biologia reprodutiva da Agouti paca criada em cativeiro. Os resultados demonstraram que, a duração média do ciclo estral foi de 32,5 + 3,7 dias e o período gestacional de 148,6 + 4,8 dias. O intervalo entre partos foi de 224,5 + 52,2 dias e o primeiro cio pós-parto foi de 25,6 + 8,8 dias. A maioria (55,6 % das fêmeas apresentou dois partos por ano, com o nascimento de um filhote por parto, sendo 44,7 % fêmeas e 55,3 % machos. Ao nascer o peso médio das fêmeas foi de 605,9 + 87,5 g e dos machos 736,7 + 108,4 g (P The objective of this paper was to study the reproductive biology of the Agouti paca raised in captivity. It was observed that the estrous cycle average was 32.5 + 3.7 days, gestation length 148.6 + 4.8 days, parturition interval 224.5 + 52.2 days, and the first post-partum 25.6 + 8.8 days. It was also observed that 55.5% of the females presented two parturitions per year with one young per parturition, of which 44.7% were females and 55.3% were males. The birth weight was 605.9 + 87.8 g for females and 736.7 + 108.4 g for males (P<0.05. Puberty in females occurred between 8 to 12 months; for this, however, more detailed investigations are necessary.

  3. Teriflunomide attenuates immunopathological changes in the Dark Agouti rat model of experimental autoimmune encephalomyelitis

    Directory of Open Access Journals (Sweden)

    Garth E. Ringheim

    2013-10-01

    Full Text Available Teriflunomide is an oral disease-modifying therapy recently approved in several locations for relapsing forms of multiple sclerosis. To gain insight into the effects of teriflunomide, immunocyte population changes were measured during progression of experimental autoimmune encephalomyelitis in Dark Agouti rats. Treatment with teriflunomide attenuated levels of spinal cord-infiltrating T cells, natural killer cells, macrophages, and neutrophils. Teriflunomide also mitigated the disease-induced changes in immune cell populations in the blood and spleen suggesting an inhibitory effect on pathogenic immune responses.

  4. Teriflunomide attenuates immunopathological changes in the dark agouti rat model of experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Ringheim, Garth E; Lee, Lan; Laws-Ricker, Lynn; Delohery, Tomas; Liu, Li; Zhang, Donghui; Colletti, Nicholas; Soos, Timothy J; Schroeder, Kendra; Fanelli, Barbara; Tian, Nian; Arendt, Christopher W; Iglesias-Bregna, Deborah; Petty, Margaret; Ji, Zhongqi; Qian, George; Gaur, Rajula; Weinstock, Daniel; Cavallo, Jean; Telsinskas, Juventas; McMonagle-Strucko, Kathleen

    2013-01-01

    Teriflunomide is an oral disease-modifying therapy recently approved in several locations for relapsing-remitting multiple sclerosis. To gain insight into the effects of teriflunomide, immunocyte population changes were measured during progression of experimental autoimmune encephalomyelitis in Dark Agouti rats. Treatment with teriflunomide attenuated levels of spinal cord-infiltrating T cells, natural killer cells, macrophages, and neutrophils. Teriflunomide also mitigated the disease-induced changes in immune cell populations in the blood and spleen suggesting an inhibitory effect on pathogenic immune responses.

  5. Therapeutic effect of nucleoside analogs on experimental autoimmune encephalomyelitis in dark agouti rats

    Directory of Open Access Journals (Sweden)

    Stojkov Danijela

    2006-01-01

    Full Text Available Experimental autoimmune encephalomyelitis (EAE is a commonly used animal model of the human neurological disorder multiple sclerosis. The purpose of the present study was to investigate the effect of combined treatment with two nucleoside analogs, ribavirin and tiazofurin, on development of EAE actively induced in highly susceptible dark agouti rats. The obtained results showed that ribavirin and tiazofurin applied either separately or in combination from the onset of the firstsymptoms of EAE after its induction (therapeutic treatment significantly suppressed EAE’s clinical symptoms. However, the most pronounced effect was gained with combined treatment, probably as a result of synergistic/additive action.

  6. An obesity-dependent lactation defect in the viable yellow agouti mouse is associated with mammary inflammation

    Science.gov (United States)

    Maternal obesity is known to delay lactogenesis in breast-feeding women, as well as negatively impact lactation in other species. Obesity is also understood to be associated with inflammation. Work with the viable yellow agouti (Avy) mouse in our laboratory has documented a lactation defect in obese...

  7. Liver-specific expression of the agouti gene in transgenic mice promotes liver carcinogenesis in the absence of obesity and diabetes

    Science.gov (United States)

    Kuklin, Alexander I; Mynatt, Randall L; Klebig, Mitchell L; Kiefer, Laura L; Wilkison, William O; Woychik, Richard P; Michaud, Edward J

    2004-01-01

    Background The agouti protein is a paracrine factor that is normally present in the skin of many species of mammals. Agouti regulates the switch between black and yellow hair pigmentation by signalling through the melanocortin 1 receptor (Mc1r) on melanocytes. Lethal yellow (Ay) and viable yellow (Avy) are dominant regulatory mutations in the mouse agouti gene that cause the wild-type protein to be produced at abnormally high levels throughout the body. Mice harboring these mutations exhibit a pleiotropic syndrome characterized by yellow coat color, obesity, hyperglycemia, hyperinsulinemia, and increased susceptibility to hyperplasia and carcinogenesis in numerous tissues, including the liver. The goal of this research was to determine if ectopic expression of the agouti gene in the liver alone is sufficient to recapitulate any aspect of this syndrome. For this purpose, we generated lines of transgenic mice expressing high levels of agouti in the liver under the regulatory control of the albumin promoter. Expression levels of the agouti transgene in the liver were quantified by Northern blot analysis. Functional agouti protein in the liver of transgenic mice was assayed by its ability to inhibit binding of the α-melanocyte stimulating hormone (αMSH) to the Mc1r. Body weight, plasma insulin and blood glucose levels were analyzed in control and transgenic mice. Control and transgenic male mice were given a single intraperitoneal injection (10 mg/kg) of the hepatocellular carcinogen, diethylnitrosamine (DEN), at 15 days of age. Mice were euthanized at 36 or 40 weeks after DEN injection and the number of tumors per liver and total liver weights were recorded. Results The albumin-agouti transgene was expressed at high levels in the livers of mice and produced a functional agouti protein. Albumin-agouti transgenic mice had normal body weights and normal levels of blood glucose and plasma insulin, but responded to chemical initiation of the liver with an increased

  8. Liver-specific expression of the agouti gene in transgenic mice promotes liver carcinogenesis in the absence of obesity and diabetes

    Directory of Open Access Journals (Sweden)

    Kiefer Laura L

    2004-06-01

    Full Text Available Abstract Background The agouti protein is a paracrine factor that is normally present in the skin of many species of mammals. Agouti regulates the switch between black and yellow hair pigmentation by signalling through the melanocortin 1 receptor (Mc1r on melanocytes. Lethal yellow (Ay and viable yellow (Avy are dominant regulatory mutations in the mouse agouti gene that cause the wild-type protein to be produced at abnormally high levels throughout the body. Mice harboring these mutations exhibit a pleiotropic syndrome characterized by yellow coat color, obesity, hyperglycemia, hyperinsulinemia, and increased susceptibility to hyperplasia and carcinogenesis in numerous tissues, including the liver. The goal of this research was to determine if ectopic expression of the agouti gene in the liver alone is sufficient to recapitulate any aspect of this syndrome. For this purpose, we generated lines of transgenic mice expressing high levels of agouti in the liver under the regulatory control of the albumin promoter. Expression levels of the agouti transgene in the liver were quantified by Northern blot analysis. Functional agouti protein in the liver of transgenic mice was assayed by its ability to inhibit binding of the α-melanocyte stimulating hormone (αMSH to the Mc1r. Body weight, plasma insulin and blood glucose levels were analyzed in control and transgenic mice. Control and transgenic male mice were given a single intraperitoneal injection (10 mg/kg of the hepatocellular carcinogen, diethylnitrosamine (DEN, at 15 days of age. Mice were euthanized at 36 or 40 weeks after DEN injection and the number of tumors per liver and total liver weights were recorded. Results The albumin-agouti transgene was expressed at high levels in the livers of mice and produced a functional agouti protein. Albumin-agouti transgenic mice had normal body weights and normal levels of blood glucose and plasma insulin, but responded to chemical initiation of the liver

  9. Liver-specific expression of the agouti gene in transgenic mice promotes liver carcinogenesis in the absence of obesity and diabetes

    Energy Technology Data Exchange (ETDEWEB)

    Kuklin, Alexander [ORNL; Mynatt, Randall [ORNL; Klebig, Mitch [ORNL; Kiefer, Laura [Glaxo Wellcome, Research Triangle Park, NC; Wilkison, William O [Glaxo Wellcome, Research Triangle Park, NC; Woychik, Richard P [Jackson Laboratory, The, Bar Harbor, ME; Michaud III, Edward J [ORNL

    2004-01-01

    Background: The agouti protein is a paracrine factor that is normally present in the skin of many species of mammals. Agouti regulates the switch between black and yellow hair pigmentation by signalling through the melanocortin 1 receptor (Mc1r) on melanocytes. Lethal yellow (Ay) and viable yellow (Avy) are dominant regulatory mutations in the mouse agouti gene that cause the wild- ype protein to be produced at abnormally high levels throughout the body. Mice harboring these mutations exhibit a pleiotropic syndrome characterized by yellow coat color, obesity, hyperglycemia, hyperinsulinemia, and increased susceptibility to hyperplasia and carcinogenesis in numerous tissues, including the liver. The goal of this research was to determine if ectopic expression of the agouti gene in the liver alone is sufficient to recapitulate any aspect of this syndrome. For this purpose, we generated lines of transgenic mice expressing high levels of agouti in the liver under the regulatory control of the albumin promoter. Expression levels of the agouti transgene in the liver were quantified by Northern blot analysis. Functional agouti protein in the liver of transgenic mice was assayed by its ability to inhibit binding of the -melanocyte stimulating hormone ( MSH) to the Mc1r. Body weight, plasma insulin and blood glucose levels were analyzed in control and transgenic mice. Control and transgenic male mice were given a single intraperitoneal injection (10 mg/kg) of the hepatocellular carcinogen, diethylnitrosamine (DEN), at 15 days of age. Mice were euthanized at 36 or 40 weeks after DEN injection and the number of tumors per liver and total liver weights were recorded. Results: The albumin-agouti transgene was expressed at high levels in the livers of mice and produced a functional agouti protein. Albumin-agouti transgenic mice had normal body weights and normal levels of blood glucose and plasma insulin, but responded to chemical initiation of the liver with an increased number

  10. BIOMETRY OF PACA NEWBORNS BRED IN CAPTIVITY(AGOUTI PACA, LINNAEUS, 1766 NOTA CIENTÍFICA: BIOMETRIA DOS NEONATOS DE PACA CRIADOS EM CATIVEIRO (AGOUTI PACA, LINNAEUS, 1766

    Directory of Open Access Journals (Sweden)

    Júlio Carlos Canola

    2007-12-01

    Full Text Available

    Biometry provides important data on weight and length of wild animal newborns. After ultrasound pregnancy detection, 22 female pacas were separated in individual bails and kept until weaning of newborns. Newborns were measured with a metric tape (between the tips of the muzzle rostrally and the tail distally and weighted in a digital weight scale. Considering males and females, the average newborn length (average length ± standard deviation was 33.37 ± 0.57cm. Among males, the average weight was 33.30 ± 0.52 cm and among females 33.45 ± 0.62cm. Considering males and females, newborns weighted (average weight ± standard deviation 741.14 ± 51.23g. Among males, average weight was 717.75 ± 49.06g and among females 764.53 ± 53.40g. Female newborns are higher and heavier than males, but averages of weight and length of males and females did not differ themselves by the Tukey test (P<0.05.

    Key-words: Agouti paca, biometry, newborns.

    A biometria proporciona dados importantes no peso e comprimento de neonatos de animais selvagens. Após detecção ultra-sonográfica da prenhez, 22 pacas fêmeas foram separadas em baias individuais e mantidas até o desmame dos filhotes. Os neonatos eram medidos com uma fita métrica flexível (entre as extremidades do focinho e da caudal e então pesados em balança digital de precisão. Considerando-se machos e fêmeas, o comprimento dos neonatos (comprimento ± desvio padrão foi 33,37 ± 0,57 cm. Entre os machos, o comprimento médio foi 33,30 ± 0,52 cm e entre as fêmeas foi de 33,45 ± 0,62 cm. Em relação ao peso e considerando-se machos e fêmeas, os neonatos pesavam (peso ± desvio padrão 741,14 ± 51,23g. Entre os machos, o peso médio foi 717,75 ± 49,06g e entre as fêmeas 764,53 ± 53,40g. Os neonatos fêmeas são maiores e mais pesados que os neonatos machos de paca, mas as médias de peso e de comprimento de machos e fêmeas n

  11. Recovery and cryopreservation of epididymal sperm from agouti (Dasiprocta aguti) using powdered coconut water (ACP-109c) and Tris extenders.

    Science.gov (United States)

    Silva, M A; Peixoto, G C X; Santos, E A A; Castelo, T S; Oliveira, M F; Silva, A R

    2011-10-01

    The objective was to compare the use of powdered coconut water (ACP-109c; ACP Biotecnologia, Fortaleza, CE, Brazil) and Tris extenders for recovery and cryopreservation of epididymal sperm from agouti. The caudae epididymus and proximal ductus deferens from 10 sexually mature agoutis were subjected to retrograde washing using ACP-109c (ACP Biotecnologia) or Tris. Epididymal sperm were evaluated for motility, vigor, sperm viability, membrane integrity, and morphology. Samples were centrifuged, and extended in the same diluents plus egg yolk (20%) and glycerol (6%), frozen in liquid nitrogen, and subsequently thawed at 37°C for 1 min, followed by re-evaluation of sperm characteristics. The two extenders were similarly efficient for epididymal recovery, with regard to the number and quality of sperm recovered. However, for both extenders, sperm quality decreased (P Biotecnologia) group, which was significantly better than 9.7 ± 2.6% motile sperm with 1.2 ± 0.3 vigor in Tris. In conclusion, agouti epididymal sperm were successfully recovered using either ACP-109c (ACP Biotecnologia) or Tris extenders; however, ACP-109c (ACP Biotecnologia) was a significantly better extender for processing and cryopreserving these sperm. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Comparison of electroretinographic responses between two different age groups of adult Dark Agouti rats.

    Science.gov (United States)

    Fu, Lin; Lo, Amy Cheuk Yin; Lai, Jimmy Shiu Ming; Shih, Kendrick Co

    2015-01-01

    To describe and compare the differences in electroretinographic responses between two different age groups of adult Dark Agouti (DA) rats and to better understand the effect of age on retinal histology and function. The electroretinographic responses of two different age groups of adult DA rats were compared. Animals were divided into younger adult DA rats 10-12wk (n=8) and older adult DA rats 17-19wk (n=8). Full field electroretinography (ERG) was recorded simultaneously from both eyes after dark adaption and light adaption and parameters including the positive scotopic threshold response (pSTR), negative scotopic threshold response (nSTR), scotopic a-wave, b-wave, photopic a-wave, b-wave and photopic negative response (PhNR) were compared between groups. The older adult rats displayed lower stimulation thresholds of the STRs (pSTR and nSTR) and higher amplitudes of pSTR, scotopic a-wave and b-wave, photopic b-wave and PhNR amplitudes, with shorter implicit times. Photopic a-wave amplitudes were however higher in the younger adult rats. In summary, for the rod system, photoreceptor, bipolar cell and RGC activity was enhanced in the older adult rats. For the cone system, RGC and bipolar cell activity was enhanced, while photoreceptor activity was depressed in the older adult rats. Such age-related selective modification of retinal cell function needs to be considered when conducting ophthalmic research in adult rats.

  13. Wnt10b inhibits obesity in ob/ob and agouti mice.

    Science.gov (United States)

    Wright, Wendy S; Longo, Kenneth A; Dolinsky, Vernon W; Gerin, Isabelle; Kang, Sona; Bennett, Christina N; Chiang, Shian-Huey; Prestwich, Tyler C; Gress, Catherine; Burant, Charles F; Susulic, Vedrana S; MacDougald, Ormond A

    2007-02-01

    The Wnt family of secreted signaling molecules has profound effects on diverse developmental processes, including the fate of mesenchymal progenitors. While activation of Wnt signaling blocks adipogenesis, inhibition of endogenous Wnt/beta-catenin signaling by Wnt10b promotes spontaneous preadipocyte differentiation. Transgenic mice with expression of Wnt10b from the FABP4 promoter (FABP4-Wnt10b) have less adipose tissue when maintained on a normal chow diet and are resistant to diet-induced obesity. Here we demonstrate that FABP4-Wnt10b mice largely avert weight gain and metabolic abnormalities associated with genetic obesity. FABP4-Wnt10b mice do not gain significant body weight on the ob/ob background, and at 8 weeks of age, they have an approximately 70% reduction in visceral and subcutaneous adipose tissues compared with ob/ob mice. Similarly, on the lethal yellow agouti (A(y)) background, FABP4-Wnt10b mice have 50-70% less adipose tissue weight and circulating leptin at 5 months of age. Wnt10b-Ay mice are more glucose tolerant and insulin sensitive than A(y) controls, perhaps due to reduced expression and circulation of resistin. Reduced expression of inflammatory cytokines may also contribute to improved glucose homeostasis.

  14. The agouti-related peptide binds heparan sulfate through segments critical for its orexigenic effects.

    Science.gov (United States)

    Palomino, Rafael; Lee, Hsiau-Wei; Millhauser, Glenn L

    2017-05-05

    Syndecans potently modulate agouti-related peptide (AgRP) signaling in the central melanocortin system. Through heparan sulfate moieties, syndecans are thought to anchor AgRP near its receptor, enhancing its orexigenic effects. Original work proposed that the N-terminal domain of AgRP facilitates this interaction. However, this is not compatible with evidence that this domain is posttranslationally cleaved. Addressing this long-standing incongruity, we used calorimetry and magnetic resonance to probe interactions of AgRP peptides with glycosaminoglycans, including heparan sulfate. We show that mature, cleaved, C-terminal AgRP, not the N-terminal domain, binds heparan sulfate. NMR shows that the binding site consists of regions distinct from the melanocortin receptor-binding site. Using a library of designed AgRP variants, we find that the strength of the syndecan interaction perfectly tracks orexigenic action. Our data provide compelling evidence that AgRP is a heparan sulfate-binding protein and localizes critical regions in the AgRP structure required for this interaction. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Coordinated Regulation of Hepatic Energy Stores by Leptin and Hypothalamic Agouti-Related Protein

    Science.gov (United States)

    Warne, James P.; Varonin, Jillian M.; Nielsen, Sofie S.; Olofsson, Louise E.; Kaelin, Christopher B.; Chua, Streamson; Barsh, Gregory S.; Koliwad, Suneil K.

    2013-01-01

    Like obesity, prolonged food deprivation induces severe hepatic steatosis; however, the functional significance of this phenomenon is not well understood. In this study, we show that the fall in plasma leptin concentration during fasting is required for the development of hepatic steatosis in mice. Removal of leptin receptors from AGRP neurons diminishes fasting-induced hepatic steatosis. Furthermore, the suppressive effects of leptin on fasting-induced hepatic steatosis are absent in mice lacking the gene encoding agouti-related protein (Agrp), suggesting that this function of leptin is mediated by AGRP. Prolonged fasting leads to suppression of hepatic sympathetic activity, increased expression of acyl CoA:diacylglycerol acyltransferase-2 in the liver, and elevation of hepatic triglyceride content and all of these effects are blunted in the absence of AGRP. AGRP deficiency, despite having no effects on feeding or body adiposity in the free-fed state, impairs triglyceride and ketone body release from the liver during prolonged fasting. Furthermore, reducing CNS Agrp expression in wild-type mice by RNAi protected against the development of hepatic steatosis not only during starvation, but also in response to consumption of a high-fat diet. These findings identify the leptin-AGRP circuit as a critical modulator of hepatic triglyceride stores in starvation and suggest a vital role for this circuit in sustaining the supply of energy from the liver to extrahepatic tissues during periods of prolonged food deprivation. PMID:23864684

  16. Acute circuit-resistance exercise increases expression of lymphocyte agouti-related protein in young women.

    Science.gov (United States)

    Ghanbari-Niaki, Abbass; Saghebjoo, Marziyeh; Rashid-Lamir, Amir; Fathi, Rozita; Kraemer, Robert R

    2010-03-01

    Exercise-induced leukocytosis and lymphocytosis is accompanied by up-regulation and down-regulation of hundreds of genes in white blood cells (WBCs). Agouti-related protein (AgRP) is an orexigenic peptide secreted predominantly from the arcuate nucleus in the hypothalamus. AgRP affects feeding behavior and plays a role in energy and glucose homeostasis and adiposity. The purpose of the study was to determine effects of circuit resistance exercise (CRE) (9 exercises, 25 s per exercise) at different intensities on peripheral blood lymphocyte (PBL) AgRP mRNA expression and its concentrations in lymphocytes and plasma. Twenty-five young female college students were randomly divided into five groups: control, 40% 1-repetition maximum (1-RM), 60% 1-RM, 80% 1-RM and combined (40 + 60 + 80% 1-RM) loads. Peripheral blood mononuclear cells were isolated by a lymphocyte density gradient centrifugation method for AgRP mRNA expression. Lymphocyte ATP, glycogen, AgRP, growth hormone (GH), and plasma AgRP, GH and glucose concentrations were measured. CRE increased AgRP mRNA lymphocyte expression significantly (P exercise stress.

  17. Agouti signalling protein (ASIP) gene: molecular cloning, sequence characterisation and tissue distribution in domestic goose.

    Science.gov (United States)

    Zhang, J; Wang, C; Liu, Y; Liu, J; Wang, H Y; Liu, A F; He, D Q

    2016-06-01

    Agouti signalling protein (ASIP) is an endogenous antagonist of melanocortin-1 receptor (MC1R) and is involved in the regulation of pigmentation in mammals. The objective of this study was to identify and characterise the ASIP gene in domestic goose. The goose ASIP cDNA consisted of a 44-nucleotide 5'-terminal untranslated region (UTR), a 390-nucleotide open-reading frame (ORF) and a 45-nucleotide 3'-UTR. The length of goose ASIP genomic DNA was 6176 bp, including three coding exons and two introns. Bioinformatic analysis indicated that the ORF encodes a protein of 130 amino-acid residues with a molecular weight of 14.88 kDa and an isoelectric point of 9.73. Multiple sequence alignments and phylogenetic analysis showed that the amino-acid sequence of ASIP was conserved in vertebrates, especially in the avian species. RT-qPCR showed that the goose ASIP mRNA was differentially expressed in the pigment deposition tissues, including eye, foot, feather follicle, skin of the back, as well as in skin of the abdomen. The expression level of the ASIP gene in skin of the abdomen was higher than that in skin of the back. Those findings will contribute to further understanding the functions of the ASIP gene in geese plumage colouring.

  18. Infección inducida en el roedor selvático Dasyprocta leporina (Rodentia: Dasyproctidae, con huevos larvados de Lagochilascaris minor (Nematoda: Ascarididae Induced infection in the wild rodent Dasyprocta leporina (Rodentia: Dasyproctidae with larval eggs of Lagochilascaris minor (Nematoda: Ascarididae

    Directory of Open Access Journals (Sweden)

    S. Gregorio

    1990-12-01

    Full Text Available Ejemplares de Dasyprocta leporina Linnaeus, 1758 fueron criados alejados de su ambiente natural. A los 3 ó 4 meses de edad, se los inoculó por vía oral con huevos de Lagochilascaris minor Leiper, 1909 obtenidos de una paciente nativa. Los huevos se los incubó por más de 80 dias, para que de ellos fuese posible obtener por compresión mecánica, larvas que se mantuviesen vivas en medio acuoso por 48 horas o más. Sacrificados los animales a los 14 ó 46 dias posteriores a la infección, se hallaron en los músculos esqueléticos larvas ovilladas dentro de nódulos inflamatorios, los cuales no presentaban reacción a cuerpo extraño, abscedación o calcificación. El desarollo de los nódulos no parecía afectar la normalidad de los hospedadores. Las larvas obtenidas eran similares a las descritas por SPRENT como de tercer estadio para estos helmintos. Ratones blancos infectados con material similar, no presentaron nódulos en sus músculos ni se pudo recuperar de sus tejidos larva alguna. Por los hallazgos obtenidos con la infección de estos animales, se postula que el helminto no posee ciclo pulmonar y que su desarrollo requiere de un hospedador intermediario.Specimens of Dasyprocta leporina (Linnaeus, 1758 were raised out their natural environment. At three to four months of age they were orally inoculated with Lagochilascaris minor (Leiper, 1909 eggs obtained from a native patient. The eggs were incubated for more than 80 days so that it was possible to obtain, by mechanical compression, larvae that could be maintained alive in liquid medium for 48 hours or more. The animals were sacrificed 14-46 days after infection and tangled larva in inflammatory nodules were found in skeletal muscle without foreign body reaction, abscess formation or calcification. The development of the nodules did not seem to affect the hosts. The larvae obtained were similar to those described by SPRENT as the third stage of these helminths. When white mice were

  19. Actividad ovárica del tepezcuintle Agouti paca (Rodentia: Agoutidae en cautiverio

    Directory of Open Access Journals (Sweden)

    Rubén C Montes Pérez

    2006-09-01

    Full Text Available Se caracterizó la actividad ovárica de A. paca por medio de perfiles hormonales y estructuras ováricas. Se muestrearon ocho hembras (siete adultas y una juvenil en el criadero de la Facultad de Medicina Veterinaria y Zootecnia en el estado de Yucatán, México, durante aproximadamente dos meses. Se recolectaron muestras sanguíneas cada 3 y 6 días en animales anestesiados. Se estimaron los niveles de progesterona (P4 y 17 β estradiol (E2 sanguνneos por radioinmunoanαlisis. Las estructuras ováricas de animales muertos durante el periodo de muestreo fueron analizadas macro y microscópicamente. El ciclo ovárico duró 29±8.4 días, con niveles de 1.61±0.65 ng/ml para P4 y de 39±24 pg/ml para E2 durante la fase folicular, y de 6.18±3.70 ng/ml y 29±16 pg/ml para P4 y E2 respectivamente, en la fase luteal. Hubo diferencias (pOvarian activity of Agouti paca (Rodentia: Agoutidae under captivity. The ovarian activity of Agouti paca was characterized by hormonal profiles and ovarian structures. Samples of blood were taken from eight females (seven adults and one juvenile at the breeding grounds of the Facultad de Medicina Veterinaria y Zootecnia in Yucatán, México. Sampling lasted approximately two months and was done every three and six days. Blood was collected from anesthetized animals, and the levels of progesterone (P4 and 17 β estradiol (E2 were analized by radioimmunoassay technique. Macroscopic and microscopic analyses were carried out in ovaries of dead animals. The estrous cycle lasted 29±8.4 days, levels of 1.61±0.65 ng/ml for P4 and 39±24 pg/ml for E2 were observed for a follicular phase, 6.18±3.70 ng/ml and 29±16 pg/ml for P4 and E2 respectively in the luteal phase. Statistically significant differences were found between phases for P4 but not for E2. The presence of extragonadal steroids with levels of P4 of 1.9±0.77 ng/ml and E2 of 22±17 pg/ml were observed, which are not produced by the effects of managing stress

  20. Regulation of plasma agouti-related protein and its relationship with hunger in lean and obese men.

    Science.gov (United States)

    Hazell, Tom J; Sawula, Laura; Edgett, Brittany A; Walsh, Jeremy J; Gurd, Brendon J

    2016-12-01

    Agouti-related protein (AgRP) is an orexigenic (appetite stimulating) neuropeptide suggested to exert tonic control over long-term energy balance. While some have speculated AgRP is not involved in the episodic (i.e. meal to meal energy intake) control, acute decreases in plasma agouti-related protein (AgRP) following a meal have been observed in humans in a role consistent with episodic control for AgRP. Whether changes in plasma AgRP are associated with episodic, and/or tonic changes in appetite has yet to be directly examined. The present study examined the relationship between agouti-related protein (AgRP), leptin and the regulation of appetite following a 48-h fast and an acute meal challenge. Blood samples were obtained from young lean and obese men before and after a 48 h fast (lean n = 10; obese n = 7). Fasting resulted in an increase in AgRP and a decrease in leptin with these changes being greater in lean than obese. In addition, blood samples were obtained from lean men before and 1, 2, 3 and 4 h after a meal (n = 8). Following a meal, AgRP was reduced from 2 to 4 h, a change that was dissociated from both leptin and subjective measures of hunger and satiety. These results demonstrate that AgRP is not associated with changes in hunger or satiety, and can change without corresponding changes in leptin. This suggests that AgRP may not be involved in the episodic control of appetite and the release of AgRP may involve signals other than leptin. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Neither Agouti-Related Protein nor Neuropeptide Y Is Critically Required for the Regulation of Energy Homeostasis in Mice

    OpenAIRE

    Qian, Su; Chen, Howard; Weingarth, Drew; Trumbauer, Myrna E.; Novi, Dawn E.; Guan, Xiaoming; Yu, Hong; Shen, Zhu; Feng, Yue; Frazier, Easter; Chen, Airu; Camacho, Ramon E.; Shearman, Lauren P; Gopal-Truter, Shobhna; MacNeil, Douglas J.

    2002-01-01

    Agouti-related protein (AgRP), a neuropeptide abundantly expressed in the arcuate nucleus of the hypothalamus, potently stimulates feeding and body weight gain in rodents. AgRP is believed to exert its effects through the blockade of signaling by α-melanocyte-stimulating hormone at central nervous system (CNS) melanocortin-3 receptor (Mc3r) and Mc4r. We generated AgRP-deficient (Agrp−/−) mice to examine the physiological role of AgRP. Agrp−/− mice are viable and exhibit normal locomotor activ...

  2. Histochemical Characterization, Distribution and Morphometric Analysis of NADPH Diaphorase Neurons in the Spinal Cord of the Agouti

    Science.gov (United States)

    Freire, Marco Aurélio M.; Tourinho, Suzane C.; Guimarães, Joanilson S.; Oliveira, Jorge Luiz F.; Picanço-Diniz, Cristovam W.; Gomes-Leal, Walace; Pereira, Antonio

    2008-01-01

    We evaluated the neuropil distribution of the enzymes NADPH diaphorase (NADPH-d) and cytochrome oxidase (CO) in the spinal cord of the agouti, a medium-sized diurnal rodent, together with the distribution pattern and morphometrical characteristics of NADPH-d reactive neurons across different spinal segments. Neuropil labeling pattern was remarkably similar for both enzymes in coronal sections: reactivity was higher in regions involved with pain processing. We found two distinct types of NADPH-d reactive neurons in the agouti's spinal cord: type I neurons had large, heavily stained cell bodies while type II neurons displayed relatively small and poorly stained somata. We concentrated our analysis on type I neurons. These were found mainly in the dorsal horn and around the central canal of every spinal segment, with a few scattered neurons located in the ventral horn of both cervical and lumbar regions. Overall, type I neurons were more numerous in the cervical region. Type I neurons were also found in the white matter, particularly in the ventral funiculum. Morphometrical analysis revealed that type I neurons located in the cervical region have dendritic trees that are more complex than those located in both lumbar and thoracic regions. In addition, NADPH-d cells located in the ventral horn had a larger cell body, especially in lumbar segments. The resulting pattern of cell body and neuropil distribution is in accordance with proposed schemes of segregation of function in the mammalian spinal cord. PMID:18958200

  3. [The effect of the "yellow" mutation at the mouse agouti locus on the hormonal profile of pregnancy and lactation].

    Science.gov (United States)

    Bazhan, N M; Makarova, E N

    2009-11-01

    The "yellow" mutation at the mouse agouti locus (A(y)/a-mice) results in obesity and type 2 diabetes. Maternal obesity in A(y)-mice impaired glucose tolerance in adult Agouti-negative offspring. Changes of hormone pattern during pregnancy and lactation are known to disregulate glucose metabolism in the adult progeny. The aim of the study was to assay blood levels of glucose, insulin, corticosterone and leptin during pregnancy (days 7, 13, 18) and lactation (days 1, 10, 21) in C57B1/6J mice of a/a (normal metabolism) and A(y)/a genotypes. A(y)/a-mice did not differ from a/a-mice in insulin and glucose levels during pregnancy and lactation, in corticosterone levels during pregnancy, but had higher leptin levels in pregnancy and lactation and increased corticosterone levels during lactation. A(y)/a-mice may be considered as a genetic model for studying impact of maternal leptin and corticosterone in developmental programming.

  4. Hypothalamic NPY and agouti-related protein are increased in human illness but not in Prader-Willi syndrome and other obese subjects

    NARCIS (Netherlands)

    Goldstone, Anthony P.; Unmehopa, Unga A.; Bloom, Stephen R.; Swaab, Dick F.

    2002-01-01

    Animal studies have demonstrated the importance of orexigenic NPY and agouti-related protein (AGRP) hypothalamic neurons, which are inhibited by the adipocyte hormone leptin, in the regulation of body weight and neuroendocrine secretion. We have examined NPY and AGRP neurons in postmortem human

  5. Atributos de qualidade da carne de paca (Agouti paca: perfil sensorial e força de cisalhamento Quality attributes of paca meat (Agouti paca: sensory profile and shear force

    Directory of Open Access Journals (Sweden)

    C. Gomes

    2013-04-01

    Full Text Available Avaliaram-se as características sensoriais e determinou-se a força de cisalhamento de cortes de carne de paca (Agouti paca. As análises foram realizadas nos cortes desossados de paleta, lombo e pernil de nove pacas, preparados por cocção até a temperatura interna de 70ºC. A avaliação de aspecto, cor, sabor, odor e maciez foi realizada pela aplicação de teste afetivo a 146 provadores, utilizando-se escala hedônica, e a força de cisalhamento foi determinada pela técnica Warner Bratzler. Na avaliação sensorial, os cortes de paleta, lombo e pernil de paca mostraram diferença significativa (p0,05 entre os cortes, que se mostraram igualmente macios. A carne de paca apresentou-se sensorialmente semelhante à carne suína e com boa aceitação pelos consumidores. O estudo evidenciou o potencial da paca como uma espécie silvestre para a produção comercial de carne para o mercado de carnes vermelhas ou exóticas.Sensory characteristics and shear force of paca meat (Agouti paca were assessed in this study. Analyses were performed in the bonelessshoulder,loin andhamobtained from nine paca carcassesprepared by cookinguntil reaching the internal temperatureof 70°C. The evaluation of flavor, aroma, color, appearance and tenderness was carried out by the application of an affective test using the hedonic scaleand a 146 consumer panel. Shear force was determined by the Warner-Bratzler technique. Shoulder, loin and ham had significant differences (p 0.05 among the cuts, which were similarly tender. Paca meat was found to resemble pork meat in sensory evaluation and had good acceptance by consumers. This study showed the potential of paca (Agouti paca asa wild species for meat production in the red or exotic meat market.

  6. Differentiation of hairbulb pigment cell melanosomes in compound agouti and albino locus mouse mutants (Ay, a, c2J; C57BL/6J).

    Science.gov (United States)

    Granholm, N H; Japs, R A; Kappenman, K E

    1990-01-01

    Our objective was to determine using electron microscopy how nonagouti (a), lethal yellow (Ay), and albino (c2J) genes affect the program of mouse hairbulb melanosome differentiation; 1,921 hairbulb melanosomes from four genotypes (a/a C/C = B,Ay/a C/C = Y, a/a c2J/c2J = BA, and Ay/a c2J/c2J = YA) were scored for developmental stage, length, and width. Qualitative and quantitative electron microscopy revealed the following. An albino locus-induced diminution of melanosome size suggests that the albino locus is involved in structural features of melanosomes not directly related to the synthesis and deployment of tyrosinase. Ratio data on melanosome length-to-width confirm that the agouti locus determines melanosome shape, either spherical or elliptical; melanization is not required for melanosomes to achieve their agouti-locus-determined shapes. YA (Ay/a c2J/c2J) melanosomes, characterized by poorly organized matrices, absence of active tyrosinase, unusually large membrane invaginations, and significantly smaller dimensions than those of BA (a/a c2J/c2J), showed additive effects of both Ay and c2J alleles. These data suggest that the albino locus plays a structural as well as functional (tyrosinase) role in the differentiation of mouse hairbulb melanosomes. The agouti locus, even in the absence of melanization, directs melanosome shape either via synthesis and deployment of agouti-locus-encoded matrix proteins or by other structural factors. The additive effects of Ay and c2J alleles in compound YA mutants document the importance of specific interactions both functional and structural between agouti and albino loci.

  7. Increased inhibition by agouti-related peptide of ventromedial hypothalamic neurons in rats overweight due to early postnatal overfeeding.

    Science.gov (United States)

    Li, Yuzhen; Plagemann, Andreas; Davidowa, Helga

    2002-09-13

    Melanocortins, e.g. alpha-melanocyte stimulating hormone, are involved in the central nervous regulation of body weight. Agouti-related peptide (AGRP) as an endogenous melanocortin receptor antagonist induces feeding. Overexpression leads to obesity. Rats that grow up in small litters develop persistent hyperphagia and are overweight throughout life. Changes in the neuronal activity of the ventromedial hypothalamic nucleus (VMH) that signals satiety with activation might be involved. We studied single unit activity in hypothalamic brain slices. Melanocortins activated or inhibited similarly in control and small litter rats. AGRP mainly inhibited VMH neurons of overweight rats (t-test, P inhibition of VMH neurons by AGRP in early postnatally overnourished rats might contribute to the changed regulation leading to a persistent overweight condition throughout life.

  8. VALOR AGREGADO DE LAS ESPECIES Brycon erythropterum (SÁBALO, Colossoma macropomum (GAMITANA, Arapaima gigas (PAICHE y Agouti paca (MAJAS

    Directory of Open Access Journals (Sweden)

    Doylith Vásquez Jurafo

    2012-12-01

    Full Text Available El presente trabajo tiene como objetivo  la obtención de  productos mínimamente procesados (PMP de Brycon erythropterum (SÁBALO, Colossoma macropomum (GAMITANA, Arapaima gigas (PAICHE, y Agouti paca (MAJAS congelado y empacado al vacio. Para las especies piscícolas, se ha aplicado un diseño factorial de 32 con dos factores de estudios: concentración de NaCl en la solución osmótica con tres niveles (15, 20 y 25 % y temperatura de proceso  con tres niveles de estudio (5, 10 y 15 °C. Para el Agouti paca (majas se aplico un diseño factorial completamente aleatorizado con tres factores de estudio: tiempo de proceso (30, 60 y 90 minutos, método de ahumado (ahumado líquido y ahumado en caliente y tipo de corte del músculo (partes y filetes. Para trabajar se ha diseñado y montado un deshidratador Osmótico teniendo en cuenta, diámetro de tubería, deshidratador propiamente dicho con doble chaqueta, capacidad del deshidratador en función del volumen de la Salmuera.  Todos los productos se obtuvieron  en procesos con 10 °C y tiempos entre 30 min y  90 min. El tiempo de vida en almacenamiento en las evaluaciones de aroma y color en majas tienen una vida útil de 4 meses de almacenados a -18 °C. Los análisis microbiológicos realizados a los PMP no pasan los límites de la NTS Nº 071 MINSA/DIGESA V01.

  9. VALOR AGREGADO DE LAS ESPECIES Brycon erythropterum (SÁBALO, Colossoma macropomum (GAMITANA, Arapaima gigas (PAICHE y Agouti paca (MAJAS

    Directory of Open Access Journals (Sweden)

    Doylith Vásquez Jurafo

    2012-12-01

    Full Text Available El presente trabajo tiene como objetivo la obtención de productos mínimamente procesados (PMP de Brycon erythropterum (SÁBALO, Colossoma macropomum (GAMITANA, Arapaima gigas (PAICHE, y Agouti paca (MAJAS congelado y empacado al vacio. Para las especies piscícolas, se ha aplicado un diseño factorial de 32 con dos factores de estudios: concentración de NaCl en la solución osmótica con tres niveles (15, 20 y 25 % y temperatura de proceso con tres niveles de estudio (5, 10 y 15 °C. Para el Agouti paca (majas se aplicó un diseño factorial completamente aleatorizado con tres factores de estudio: tiempo de proceso (30, 60 y 90 minutos, método de ahumado (ahumado líquido y ahumado en caliente y tipo de corte del músculo (partes y filetes. Para trabajar se ha diseñado y montado un deshidratador Osmótico teniendo en cuenta, diámetro de tubería, deshidratador propiamente dicho con doble chaqueta, capacidad del deshidratador en función del volumen de la Salmuera.  Todos los productos se obtuvieron en procesos con 10 °C y tiempos entre 30 min y 90 min. El tiempo de vida en almacenamiento en las evaluaciones de aroma y color en majas tienen una vida útil de 4 meses de almacenados a -18 °C. Los análisis microbiológicos realizados a los PMP no pasan los límites de la NTS Nº 071 MINSA/DIGESA V01.

  10. Dietary Calcium and Dairy Modulation of Oxidative Stress and Mortality in aP2-Agouti and Wild-type Mice

    Directory of Open Access Journals (Sweden)

    Antje Bruckbauer

    2009-08-01

    Full Text Available Oxidative and inflammatory stress have been implicated as major contributors to the aging process. Dietary Ca reduced both factors in short-term interventions, while milk exerted a greater effect than supplemental Ca. In this work, we examined the effects of life-long supplemental and dairy calcium on lifespan and life-span related biomarkers in aP2-agouti transgenic (model of diet-induced obesity and wild-type mice fed obesigenic diets until their death. These data demonstrate that dairy Ca exerts sustained effects resulting in attenuated adiposity, protection against age-related muscle loss and reduction of oxidative and inflammatory stress in both mouse strains. Although these effects did not alter maximum lifespan, they did suppress early mortality in wild-type mice, but not in aP2-agouti transgenic mice.

  11. Who's behind that mask and cape? The Asian leopard cat's Agouti (ASIP) allele likely affects coat colour phenotype in the Bengal cat breed.

    Science.gov (United States)

    Gershony, L C; Penedo, M C T; Davis, B W; Murphy, W J; Helps, C R; Lyons, L A

    2014-12-01

    Coat colours and patterns are highly variable in cats and are determined mainly by several genes with Mendelian inheritance. A 2-bp deletion in agouti signalling protein (ASIP) is associated with melanism in domestic cats. Bengal cats are hybrids between domestic cats and Asian leopard cats (Prionailurus bengalensis), and the charcoal coat colouration/pattern in Bengals presents as a possible incomplete melanism. The complete coding region of ASIP was directly sequenced in Asian leopard, domestic and Bengal cats. Twenty-seven variants were identified between domestic and leopard cats and were investigated in Bengals and Savannahs, a hybrid with servals (Leptailurus serval). The leopard cat ASIP haplotype was distinguished from domestic cat by four synonymous and four non-synonymous exonic SNPs, as well as 19 intronic variants, including a 42-bp deletion in intron 4. Fifty-six of 64 reported charcoal cats were compound heterozygotes at ASIP, with leopard cat agouti (A(P) (be) ) and domestic cat non-agouti (a) haplotypes. Twenty-four Bengals had an additional unique haplotype (A2) for exon 2 that was not identified in leopard cats, servals or jungle cats (Felis chaus). The compound heterozygote state suggests the leopard cat allele, in combination with the recessive non-agouti allele, influences Bengal markings, producing a darker, yet not completely melanistic coat. This is the first validation of a leopard cat allele segregating in the Bengal breed and likely affecting their overall pelage phenotype. Genetic testing services need to be aware of the possible segregation of wild felid alleles in all assays performed on hybrid cats. © 2014 The Authors. Animal Genetics published by John Wiley & Sons Ltd on behalf of Stichting International Foundation for Animal Genetics.

  12. SiRNA-mediated silencing of the diencephalic thyrotropin-releasing hormone precursor gene decreases the arterial blood pressure in the obese agouti mice.

    Science.gov (United States)

    Landa, Maria Silvina; Schuman, Mariano Luis; Burgueno, Adriana; Alvarez, Azucena Laura; Garcia, Silvia Ines; Pirola, Carlos Jose

    2007-05-01

    Obesity is associated with increased cardiovascular morbidity and mortality, in part through development of hypertension. Leptin promotes weight loss by reducing food intake and increasing energy expenditure through sympathetic stimulation. It also counteracts the starvation-induced suppression of thyroid hormone by up-regulating the expression of TRH. On the other hand, it is known that the extrahypothalamic TRH system participates in cardiovascular function modulating sympathetic system activity. In order to challenge the testable hypothesis that obesity may raise arterial blood pressure (ABP) through TRH system activation, we herein analyze the participation of the TRH system in the elevation of ABP in the obese agouti yellow mice. These mice are characterized by resistance to the weight reducing effect of leptin although they show a preserved sympathetic response to leptin along with a mild hypertension compared with the control strain (121+/-2 vs 102+/-2 mmHg, p less than 0.001, n=10). We report here that hyperleptinemic agouti mice showed a 1.8-fold elevation of diencephalic TRH content compared with controls, and we demonstrate that a long lasting specific inhibition of TRH system by icv treatment with siRNA against preproTRH normalizes systolic ABP independently of the thyroid status. These results suggest that the interaction leptin-diencephalic TRH may be one of the mechanisms involved in the mild hypertension of the obese agouti mice.

  13. Teriflunomide reduces behavioral, electrophysiological, and histopathological deficits in the Dark Agouti rat model of experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Merrill, Jean E; Hanak, Susan; Pu, Su-Fen; Liang, Jinjun; Dang, Chelsea; Iglesias-Bregna, Deborah; Harvey, Brian; Zhu, Bin; McMonagle-Strucko, Kathleen

    2009-01-01

    Teriflunomide is an orally available anti-inflammatory drug that prevents T and B cell proliferation and function by inhibition of dihydroorotate dehydrogenase. It is currently being developed for the treatment of multiple sclerosis (MS). We report here for the first time the anti-inflammatory effects of teriflunomide in the Dark Agouti rat model of experimental autoimmune encephalomyelitis (EAE). Neurological evaluation demonstrated that prophylactic dosing of teriflunomide at 3 and 10 mg/kg delayed disease onset and reduced maximal and cumulative scores. Therapeutic administration of teriflunomide at doses of 3 or 10 mg/kg at disease onset significantly reduced maximal and cumulative disease scores as compared to vehicle treated rats. Dosing teriflunomide at disease remission, at 3 and 10 mg/kg, reduced the cumulative scores for the remaining course of the disease. Teriflunomide at 10 mg/kg significantly reduced inflammation, demyelination, and axonal loss when dosed prophylactically or therapeutically. In electrophysiological somatosensory evoked potential studies, therapeutic administration of teriflunomide, at the onset of disease, prevented both a decrease in waveform amplitude and an increase in the latency to waveform initiation in EAE animals compared to vehicle. Therapeutic dosing with teriflunomide at disease remission prevented a decrease in evoked potential amplitude, prevented an increase in latency, and enhanced recovery time within the CNS.

  14. Origin of agouti-melanistic polymorphism in Wild Black Rats (Rattus rattus) inferred from Mc1r gene sequences.

    Science.gov (United States)

    Kambe, Yoshikazu; Tanikawa, Tsutomu; Matsumoto, Yasuharu; Tomozawa, Morihiko; Aplin, Ken P; Suzuki, Hitoshi

    2011-08-01

    We examined nucleotide changes that underlie coat color variation in Black Rats (the Rattus rattus species complex), which show polymorphism in dorsal fur color, including either grayish brown (agouti) or black (melanistic) forms. We examined the full coding sequence of a gene known to produce melanism in other vertebrates-melanocortin-1-receptor gene Mc1r (954 bp) -using samples of both R. rattus (with 2n = 38) and its close relative Asian Black Rat (R. tanezumi; 2n = 42). We used 61 specimens from Japan with karyotype-known individuals and four samples from Pakistan. We found 11 allele sequences and constructed a network tree that shows two distinct clusters, with allelic segregation according to karyotype and by inference, representing the two species. We found that a nucleotide substitution from G to A at site 280, producing an amino acid change from glutamic acid to lysine, was associated with the dominant trait of the melanistic form of the coat color in R. rattus. Notably, the derived SNP 280A was found in a single allele, with the ancestral SNP 280G present in seven alleles. By contrast, all three alleles for R. tanezumi retain the ancestral SNP 280G. These results suggest a possible recent origin of melanism in R. rattus.

  15. Circulating Levels of Orexin-A, Nesfatin-1, Agouti-Related Peptide, and Neuropeptide Y in Patients with Hyperthyroidism.

    Science.gov (United States)

    Tohma, Yusuf; Akturk, Mujde; Altinova, Alev; Yassibas, Emine; Cerit, Ethem Turgay; Gulbahar, Ozlem; Arslan, Metin; Sanlier, Nevin; Toruner, Fusun

    2015-07-01

    There is insufficient information about the appetite-related hormones orexin-A, nesfatin-1, agouti-related peptide (AgRP), and neuropeptide Y (NPY) in hyperthyroidism. The aim of the present study was to investigate the effects of hyperthyroidism on the basal metabolic rate (BMR) and energy intake, orexin-A, nesfatin-1, AgRP, NPY, and leptin levels in the circulation, and their relationship with each other and on appetite. In this prospective study, patients were evaluated in hyperthyroid and euthyroid states in comparison with healthy subjects. Twenty-one patients with overt hyperthyroidism and 33 healthy controls were included in the study. Daily energy intake in the hyperthyroid state was found to be higher than that in the euthyroid state patient group (p=0.039). BMR was higher in hyperthyroid patients than the control group (p=0.018). Orexin-A was lower and nesfatin-1 was higher in hyperthyroid patients compared to the controls (phyperthyroid and euthyroid states and controls (p>0.05). Orexin-A correlated negatively with nesfatin-1 (p=0.042), BMR (p=0.013), free triiodothyronine (fT3; phyperthyroidism" was the main factor affecting orexin-A (phyperthyroidism, the orexin-A and nesfatin-1 levels are markedly affected by hyperthyroidism.

  16. Histochemical characterization, distribution and morphometric analysis of NADPH diaphorase neurons in the spinal cord of the agouti

    Directory of Open Access Journals (Sweden)

    Marco Aurelio M Freire

    2008-05-01

    Full Text Available We evaluated the neuropil distribution of the enzymes NADPH diaphorase (NADPH-d and cytochrome oxidase (CO in the spinal cord of the agouti, a medium-sized diurnal rodent, together with the distribution pattern and morphometrical characteristics of NADPH-d reactive neurons across different spinal segments. Neuropil labeling pattern was remarkably similar for both enzymes in coronal sections: reactivity was higher in regions involved with pain processing. We found two distinct types of NADPH-d reactive neurons in the agouti’s spinal cord: type I neurons had large, heavily stained cell bodies while type II neurons displayed relatively small and poorly stained somata. We concentrated our analysis on type I neurons. These were found mainly in the dorsal horn and around the central canal of every spinal segment, with a few scattered neurons located in the ventral horn of both cervical and lumbar regions. Overall, type I neurons were more numerous in the cervical region. Type I neurons were also found in the white matter, particularly in the ventral funiculum. Morphometrical analysis revealed that type I neurons located in the cervical region have dendritic trees that are more complex than those located in both lumbar and thoracic regions. In addition, NADPH-d cells located in the ventral horn had a larger cell body, especially in lumbar segments. The resulting pattern of cell body and neuropil distribution is in accordance with proposed schemes of segregation of function in the mammalian spinal cord.

  17. Trichostrongylina (Nematoda, Heligmosomoidea coparasites in Dasyprocta fuliginosa Wagler (Rodentia, Dasyproctidae from Brazil, with the re-establishment of the genus Avellaria Freitas & Lent and the description of two new species Trichostrongylina (Nematoda, Heligmosomoidea co-parasitos em Dasyprocta fuliginosa Wagler (Rodentia, Dasyproctidae do Brasil, com o restabelecimento do gênero Avellaria Freitas & Lent e a descrição de duas novas espécies

    Directory of Open Access Journals (Sweden)

    Marie C. Durette-Desset

    2006-06-01

    Full Text Available Two new tichostrongylid nematodes of the family Viannaiidae Durette-Desset & Chabaud, 1981 coparasites in Dasyprocta fuliginosa Wagler, 1832 from the State of Amazonas, Brazil, are described: Viannella trichospicula sp. nov. is differentiated from the other species of the genus by the extreme slenderness of its spicules. Avellaria intermedia sp. nov. is distinguished from the single type species Avellaria avellari Freitas & Lent, 1934, by a smaller number of cuticular ridges (17 versus 27, a higher ratio of spicule length/ body length (8% versus 5.6% and spicules with a single tip. This genus, synonymized with the genus Viannella Travassos, 1918, by Durette-Desset (1968 is re-established, the female being didelphic. It is the first record of a nematode of the family Viannaiidae in a host of the family Dasyproctidae Bonaparte, 1838.Dois novos nematóides tricostrongilídeos da família Viannaiidae Durette-Desset & Chabaud, 1981 co-parasitos em um espécime de Dasyprocta fuliginosa Wagler, 1832 do Estado do Amazonas, Brasil, são descritos: Viannella trichospicula sp. nov. distingue-se das espécies do gênero, pelos espículos extremamente delgados. Avellaria intermedia sp. nov. diferencia-se da espécie tipo e única do gênero Avellaria avellari Freitas & Lent, 1934, pelo menor número de arestas cuticulares (17 comparado a 27, pela maior relação entre o tamanho do espículo e o comprimento do corpo (8% comparado a 5,6% e espículos com extremidade única. Este gênero, que havia sido considerado sinônimo de Viannella Travassos, 1918, por Durette-Desset (1968, é restabelecido; as fêmeas são didelfas. Este é o primeiro registro de um nematóide da família Viannaiidae em um hospedeiro da família Dasyproctidae Bonaparte, 1838.

  18. INDUCCIÓN SINCRÓNICA DEL CICLO ESTRAL EN LA GUAGUA NEGRA (Agouti taczanowskii EN CAUTIVERIO SYNCHRONOUS INDUCTION OF THE ESTRAL CYCLE IN THE BLACK GUAGUA (Agouti taczanowskii IN CAPTIVITY

    Directory of Open Access Journals (Sweden)

    Luis Emilio Trujillo Aramburo

    2006-06-01

    Full Text Available Para la inducción y sincronización del ciclo estral en la guagua negra Agouti taczanowskii en cautiverio, se aplicó a cada una de seis hembras, con edades entre cuatro y siete años, un cuarto de dosis de norgestomet y 1,25 mg de valerato de estradiol. A partir del día de la aplicación del implante se les realizó medición del diámetro del orificio vulvar tres veces por semana hasta el día 52 y con igual frecuencia, a partir del día del retiro del implante, se realizó muestreo sanguíneo para determinar los niveles de progesterona por radioinmunoanálisis. El tratamiento hormonal indujo y sincronizó el ciclo estral en tres de las seis hembras tratadas, las cuales presentaron aumento en los niveles de progesterona ³ 10 ng/ml precedidos de apertura del orificio vulvar. El ciclo estral inducido tuvo una duración variable entre 11 y 29 días. El ciclo estral espontáneo que se presentó después del inducido con el tratamiento hormonal, presentó duración variable entre 10 y 30 días. Durante el tiempo de experimentación se presentó una correlación negativa entre los niveles de progesterona y el diámetro de la apertura vulvar. Se concluye que la aplicación de un implante de norgestomet acompañado de una inyección de valerato de estradiol puede inducir y sincronizar el ciclo estral en la guagua negra.To induce and synchronize the estral cycle in the black guagua Agouti taczanowskii in captivity, each of six females varying from four to seven years of age were implanted with a quarter dose of norgestomet and injected with 1,25 mg of estradiol valerate. Starting on the day of the application of the implant, the diameter of the vulvar orifice was measured three times per week until day 52, and with same frequency beginning on the day the implant was removed, blood sampling was conducted to determine progesterone levels for radioimunoassay. The hormonal treatment induced and synchronized the estral cycle in three of the six treated

  19. ANÁLISE DA ORIGEM E DISTRIBUIÇÃO DOS NERVOS PERIFÉRICOS DO PLEXO BRAQUIAL DA PACA (Agouti paca, LINNAEUS, 1766 ORIGIN AND DITRIBUTION ANALYSIS OF THE BRACHIAL PLEXUS PERIPHERAL NERVES OF PACA (Agouti paca, LINNAEUS, 1766

    Directory of Open Access Journals (Sweden)

    Sílvia Helena Brendolan Gerbasi

    2008-12-01

    Full Text Available O plexo braquial é um conjunto de nervos que surge na região medular cervicotorácica e que se distribui pelos membros torácicos e porção interna do tórax. O plexo braquial de oito pacas foi dissecado para evidenciação da origem e distribuição de seus nervos. O nervo supraescapular distribuía-se para os músculos supra e infra-espinhal, e o subescapular para o músculo subescapular. O nervo axilar ramificava-se para os músculos redondo maior, subescapular, redondo menor e deltóide. Os nervos ulnar e mediano ramificavam-se para a musculatura do antebraço, e o musculocutâneo para os músculos coracobraquial, bíceps braquial e braquial. O nervo radial abrangia o músculo tríceps braquial, tensor da fáscia do antebraço e ancôneo. O nervo torácico longo e o toracodorsal emitiam ramos para o músculo grande dorsal, e o torácico lateral para o músculo cutâneo do tronco. Os nervos peitorais craniais ramificavam-se no músculo peitoral profundo, e os nervos peitorais caudais distribuíam-se para o músculo peitoral superficial. O plexo braquial da paca é formado por doze pares de nervos com origens distintas, os quais surgem do quinto par de nervos cervicais até o segundo par de nervos torácicos, não havendo troncos ou cordões na formação destes.

    PALAVRAS-CHAVES: Agouti paca, distribuição, plexo braquial, sistema nervoso. The brachial plexus is a set of nerves originated in the cervicothoracic medular region and distributed in the thoracic limbs and inner thorax. The brachial plexus of eight pacas was dissected for study on the nerves origin and distribution. The suprascapular nerve went through the supra and infraspinal muscles and the subscapular gave off on the subscapular muscle. The axilar nerve was distributed on the teres major, subscapular, teres minor and deltoid muscles. The ulnar and the median nerves branched off on the forearm musculature, and the musculocutaneous branched on the coracobrachial

  20. Agouti-related protein is posttranslationally cleaved by proprotein convertase 1 to generate agouti-related protein (AGRP)83-132: interaction between AGRP83-132 and melanocortin receptors cannot be influenced by syndecan-3.

    Science.gov (United States)

    Creemers, John W M; Pritchard, Lynn E; Gyte, Amy; Le Rouzic, Philippe; Meulemans, Sandra; Wardlaw, Sharon L; Zhu, Xiaorong; Steiner, Donald F; Davies, Nicola; Armstrong, Duncan; Lawrence, Catherine B; Luckman, Simon M; Schmitz, Catherine A; Davies, Rick A; Brennand, John C; White, Anne

    2006-04-01

    Agouti-related protein (AGRP) plays a key role in energy homeostasis. The carboxyl-terminal domain of AGRP acts as an endogenous antagonist of the melanocortin-4 receptor (MC4-R). It has been suggested that the amino-terminal domain of AGRP binds to syndecan-3, thereby modulating the effects of carboxyl-terminal AGRP at the MC4-R. This model assumes that AGRP is secreted as a full-length peptide. In this study we found that AGRP is processed intracellularly after Arg(79)-Glu(80)-Pro(81)-Arg(82). The processing site suggests cleavage by proprotein convertases (PCs). RNA interference and overexpression experiments showed that PC1/3 is primarily responsible for cleavage in vitro, although both PC2 and PC5/6A can also process AGRP. Dual in situ hybridization demonstrated that PC1/3 is expressed in AGRP neurons in the rat hypothalamus. Moreover, hypothalamic extracts from PC1-null mice contained 3.3-fold more unprocessed full-length AGRP, compared with wild-type mice, based on combined HPLC and RIA analysis, demonstrating that PC1/3 plays a role in AGRP cleavage in vivo. We also found that AGRP(83-132) is more potent an antagonist than full-length AGRP, based on cAMP reporter assays, suggesting that posttranslational cleavage is required to potentiate the effect of AGRP at the MC4-R. Because AGRP is cleaved into distinct amino-terminal and carboxyl-terminal peptides, we tested whether amino-terminal peptides modulate food intake. However, intracerebroventricular injection of rat AGRP(25-47) and AGRP(50-80) had no effect on body weight, food intake, or core body temperature. Because AGRP is cleaved before secretion, syndecan-3 must influence food intake independently of the MC4-R.

  1. Neither agouti-related protein nor neuropeptide Y is critically required for the regulation of energy homeostasis in mice.

    Science.gov (United States)

    Qian, Su; Chen, Howard; Weingarth, Drew; Trumbauer, Myrna E; Novi, Dawn E; Guan, Xiaoming; Yu, Hong; Shen, Zhu; Feng, Yue; Frazier, Easter; Chen, Airu; Camacho, Ramon E; Shearman, Lauren P; Gopal-Truter, Shobhna; MacNeil, Douglas J; Van der Ploeg, Lex H T; Marsh, Donald J

    2002-07-01

    Agouti-related protein (AgRP), a neuropeptide abundantly expressed in the arcuate nucleus of the hypothalamus, potently stimulates feeding and body weight gain in rodents. AgRP is believed to exert its effects through the blockade of signaling by alpha-melanocyte-stimulating hormone at central nervous system (CNS) melanocortin-3 receptor (Mc3r) and Mc4r. We generated AgRP-deficient (Agrp(-/-)) mice to examine the physiological role of AgRP. Agrp(-/-) mice are viable and exhibit normal locomotor activity, growth rates, body composition, and food intake. Additionally, Agrp(-/-) mice display normal responses to starvation, diet-induced obesity, and the administration of exogenous leptin or neuropeptide Y (NPY). In situ hybridization failed to detect altered CNS expression levels for proopiomelanocortin, Mc3r, Mc4r, or NPY mRNAs in Agrp(-/-) mice. As AgRP and the orexigenic peptide NPY are coexpressed in neurons of the arcuate nucleus, we generated AgRP and NPY double-knockout (Agrp(-/-);Npy(-/-)) mice to determine whether NPY or AgRP plays a compensatory role in Agrp(-/-) or NPY-deficient (Npy(-/-)) mice, respectively. Similarly to mice deficient in either AgRP or NPY, Agrp(-/-);Npy(-/-) mice suffer no obvious feeding or body weight deficits and maintain a normal response to starvation. Our results demonstrate that neither AgRP nor NPY is a critically required orexigenic factor, suggesting that other pathways capable of regulating energy homeostasis can compensate for the loss of both AgRP and NPY.

  2. Dietary calcium regulates ROS production in aP2-agouti transgenic mice on high-fat/high-sucrose diets.

    Science.gov (United States)

    Sun, X; Zemel, M B

    2006-09-01

    We have previously demonstrated that 1alpha, 25(OH)2D3 promotes adipocyte reactive oxygen species (ROS) production. We have now evaluated whether decreasing 1alpha, 25(OH)2D3 levels by increasing dietary calcium will decrease oxidative stress in vivo. We fed low-calcium (0.4% Ca) and high-calcium (1.2% Ca from CaCO3) obesity-promoting (high sucrose/high fat) diets to aP2-agouti transgenic mice and assessed regulation of ROS production in adipose tissue and skeletal muscle. Mice on the high-calcium diet gained 50% of the body weight (P=0.04) and fat (Pcalcium diet (0.4% Ca). The high-calcium diet significantly reduced adipose intracellular ROS production by 64 and 18% (Pphosphate oxidase expression by 49% (P=0.012) and 63% (P=0.05) in visceral and subcutaneous adipose tissue, respectively. Adipocyte intracellular calcium ([Ca2+]i) levels were suppressed in mice on the high-calcium diet by 73-80% (Pcalcium diet also induced 367 and 191% increases in adipose mitochondrial uncoupling protein 2 (UCP2) expression (Pcalcium diet also suppressed 11beta-hydroxysteroid dehydrogenase (11beta-HSD) expression in visceral adipose tissue by 39% (P=0.034). 11beta-HSD expression was markedly higher in visceral vs subcutaneous adipose tissue in mice on the low-calcium diet (P=0.034), whereas no difference was observed between the fat depots in mice on the high-calcium diet. These data support a potential role for dietary calcium in the regulation of obesity-induced oxidative stress.

  3. Long-Term Effects of (--Epigallocatechin Gallate (EGCG on Pristane-Induced Arthritis (PIA in Female Dark Agouti Rats.

    Directory of Open Access Journals (Sweden)

    Anna Leichsenring

    Full Text Available Rheumatoid arthritis (RA--a widespread chronic inflammatory disease in industrialized countries--is characterized by a persistent and progressive joint destruction. The chronic pro-inflammatory state results from a mutual activation of the innate and the adaptive immune system, while the exact pathogenesis mechanism is still under discussion. New data suggest a role of the innate immune system and especially polymorphonuclear granulocytes (PMNs, neutrophils not only during onset and the destructive phase of RA but also at the chronification of the disease. Thereby the enzymatic activity of myeloperoxidase (MPO, a peroxidase strongly abundant in neutrophils, may be important: While its peroxidase activity is known to contribute to cartilage destruction at later stages of RA the almost MPO-specific oxidant hypochlorous acid (HOCl is also discussed for certain anti-inflammatory effects. In this study we used pristane-induced arthritis (PIA in Dark Agouti rats as a model for the chronic course of RA in man. We were able to shown that a specific detection of the HOCl-producing MPO activity provides a sensitive new marker to evaluate the actual systemic inflammatory status which is only partially detectable by the evaluation of clinical symptoms (joint swelling and redness measurements. Moreover, we evaluated the long-term pharmacological effect of the well-known anti-inflammatory flavonoid epigallocatechin gallate (EGCG. Thereby only upon early and continuous oral application of this polyphenol the arthritic symptoms were considerably diminished both in the acute and in the chronic phase of the disease. The obtained results were comparable to the treatment control (application of methotrexate, MTX. As revealed by stopped-flow kinetic measurements, EGCG may regenerate the HOCl-production of MPO which is known to be impaired at chronic inflammatory diseases like RA. It can be speculated that this MPO activity-promoting effect of EGCG may contribute to

  4. Ala67Thr polymorphism in the Agouti-related peptide gene is associated with inherited leanness in humans.

    Science.gov (United States)

    Marks, Daniel L; Boucher, Nathalie; Lanouette, Christian-Marc; Pérusse, Louis; Brookhart, Gregor; Comuzzie, Anthony G; Chagnon, Yvon C; Cone, Roger D

    2004-04-30

    A role for melanocortin signaling in the regulation of body weight in humans has been clearly established. Haploinsufficiency of the type 4 melanocortin receptor is associated with early-onset obesity, implying that this receptor provides an important tonic inhibition of weight gain. Agouti-related peptide (AGRP) is an endogenous antagonist of melanocortin signaling. Therefore, loss of AGRP function could lead to the expression of a lean phenotype. We investigated the potential role of AGRP in human weight regulation by examining the association between the Ala67Thr AGRP polymorphism and indices of body composition. Significant associations were found between homozygosity for this mutation (n = 8) and body composition phenotype in 874 subjects of the Quebec family study (QFS). By PCR-RFLP analysis, we have identified eight individuals who are homozygous for the 67Thr variant allele within the QFS population, where none were observed in SAFHS. The eight QFS homozygote individuals have lower weight (-16%; P = 0.02), body mass index (-17%; P = 0.01), fat free mass (-9%; P = 0.002), fat mass (FM) (-20%; P = 0.04), and leptin (-20%; P = 0.02) when compared to those carrying at least one 67Ala allele. Individuals homozygous for the 67Thr allele had a BMI that was either at or slightly below an ideal range for their age. Thus, the Ala67Thr AGRP polymorphism is associated with lower body weight in humans, with the largest effect being observed on body FM. We did not observe any difference in the stability or cellular distribution of the mutant protein in a heterologous expression system, thus the mechanism of this effect requires further investigation. Copyright 2004 Wiley-Liss, Inc.

  5. Copy number variation and missense mutations of the agouti signaling protein (ASIP) gene in goat breeds with different coat colors.

    Science.gov (United States)

    Fontanesi, L; Beretti, F; Riggio, V; Gómez González, E; Dall'Olio, S; Davoli, R; Russo, V; Portolano, B

    2009-01-01

    In goats, classical genetic studies reported a large number of alleles at the Agouti locus with effects on coat color and pattern distribution. From these early studies, the dominant A(Wt) (white/tan) allele was suggested to cause the white color of the Saanen breed. Here, we sequenced the coding region of the goat ASIP gene in 6 goat breeds (Girgentana, Maltese, Derivata di Siria, Murciano-Granadina, Camosciata delle Alpi, and Saanen), with different coat colors and patterns. Five single nucleotide polymorphisms (SNPs) were identified, 3 of which caused missense mutations in conserved positions of the cysteine-rich carboxy-terminal domain of the protein (p.Ala96Gly, p.Cys126Gly, and p.Val128Gly). Allele and genotype frequencies suggested that these mutations are not associated or not completely associated with coat color in the investigated goat breeds. Moreover, genotyping and sequencing results, deviation from Hardy-Weinberg equilibrium, as well as allele copy number evaluation from semiquantitative fluorescent multiplex PCR, indicated the presence of copy number variation (CNV) in all investigated breeds. To confirm the presence of CNV and evaluate its extension, we applied a bovine-goat cross-species array comparative genome hybridization (aCGH) experiment using a custom tiling array based on bovine chromosome 13. aCGH results obtained for 8 goat DNA samples confirmed the presence of CNV affecting a region of less that 100 kb including the ASIP and AHCY genes. In Girgentana and Saanen breeds, this CNV might cause the A(Wt) allele, as already suggested for a similar structural mutation in sheep affecting the ASIP and AHCY genes, providing evidence for a recurrent interspecies CNV. However, other mechanisms may also be involved in determining coat color in these 2 breeds. Copyright 2009 S. Karger AG, Basel.

  6. Ghrelin increases neuropeptide Y and agouti-related peptide gene expression in the arcuate nucleus in rat hypothalamic organotypic cultures.

    Science.gov (United States)

    Goto, Motomitsu; Arima, Hiroshi; Watanabe, Minemori; Hayashi, Masayuki; Banno, Ryouichi; Sato, Ikuko; Nagasaki, Hiroshi; Oiso, Yutaka

    2006-11-01

    Ghrelin, which was identified from the rat stomach, is a potent stimulant for food intake. Several lines of evidence suggest that the orexigenic action of ghrelin is mediated via the neuropeptide Y (NPY) neurons in the arcuate nucleus, although the detailed mechanisms by which ghrelin stimulates NPY neurons are not clear. In this study, we examined the gene regulation of NPY and agouti-related peptide (AGRP), another orexigenic peptide synthesized in the NPY neurons, in the arcuate nucleus by ghrelin in hypothalamic organotypic cultures. Incubation of the hypothalamic explants with ghrelin significantly increased NPY and AGRP mRNA expression in the presence, but not absence, of dexamethasone. Glucocorticoids were also necessary for ghrelin action in vivo because an intracerebroventricular injection of ghrelin significantly increased NPY and AGRP mRNA expression in the arcuate nucleus only in sham-operated, but not in adrenalectomized rats. The stimulatory effects of ghrelin on gene expression were not blocked by a sodium channel blocker tetrodotoxin in the organotypic cultures. Ghrelin also increased NPY heteronuclear (hn) RNA expression, the first transcript that has been used as an indicator for gene transcription. The stimulatory effects of ghrelin on NPY gene expression were abolished in the presence of cycloheximide, which blocks translation, suggesting that de novo protein synthesis is required for ghrelin action. These data suggest that ghrelin stimulates NPY and AGRP gene expression independently of action potentials only in the presence of glucocorticoids. Furthermore, our data demonstrate stimulatory action of ghrelin on NPY gene transcription, which requires de novo protein synthesis.

  7. Pre-obese and obese agouti mice are sensitive to the anorectic effects of peptide YY(3-36) but resistant to ghrelin.

    Science.gov (United States)

    Martin, N M; Small, C J; Sajedi, A; Patterson, M; Ghatei, M A; Bloom, S R

    2004-07-01

    The role of the melanocortin system in the feeding effects of peripheral peptide YY(3-36) (PYY(3-36)) and ghrelin was investigated using the agouti (A(y)/a) mouse as a model of abnormal melanocortin signalling. Furthermore, we examined whether the ectopic expression of agouti protein in A(y)/a mice results in complete MC4-R inhibition, by studying the effects of peripheral alpha-melanocyte-stimulating hormone (alpha-MSH) and leptin on food intake. Adult A(y)/a mice were studied in the pre-obese state (7-8 weeks) and obese state (14-15 weeks). Animals received PYY(3-36) (0.02 micromol/kg), NDP-alpha-MSH (0.2 micromol/kg), leptin (2 micromol/kg) (all 24 h fasted state) and ghrelin (0.2 micromol/kg) (fed state) by intraperitoneal (i.p.) injection. Age-matched A(y)/a controls received i.p. saline. A separate cohort of wild-type (WT), age-matched controls received the same peptide dose or saline. Food intake was measured at 1, 2, 4, 8 and 24 h post-injection and compared in all four groups. Plasma leptin-, ghrelin- and PYY-like immunoreactivity (IR) were measured using radioimmunoassay (RIA). At 2 h post-injection, PYY(3-36) reduced food intake in pre-obese and obese A(y)/a mice, whereas ghrelin had no effect. Plasma ghrelin levels were significantly reduced in pre-obese and obese A(y)/a mice compared to WT controls. Peripheral administration of NDP-alpha-MSH and leptin acutely suppressed feeding (0-2 h) in pre-obese and obese A(y)/a mice. Responsiveness of pre-obese and obese A(y)/a mice to PYY(3-36) suggests that the melanocortin system may not be essential for the anorectic effects of this peptide. Melanocortinergic antagonism by agouti protein in A(y)/a mice may be sufficient to block the effects of endogenous, but not exogenous PYY(3-36), alpha-MSH and leptin. The mechanism underlying ghrelin resistance in A(y)/a mice may result from antagonism of hypothalamic melanocortin receptors-4 by agouti protein, supporting a role for the melanocortin system in mediating

  8. A C-terminal fragment of Agouti-related protein increases feeding and antagonizes the effect of alpha-melanocyte stimulating hormone in vivo.

    Science.gov (United States)

    Rossi, M; Kim, M S; Morgan, D G; Small, C J; Edwards, C M; Sunter, D; Abusnana, S; Goldstone, A P; Russell, S H; Stanley, S A; Smith, D M; Yagaloff, K; Ghatei, M A; Bloom, S R

    1998-10-01

    Agouti-related protein (Agrp) is present in rat and human hypothalamus and is structurally related to agouti protein. Overexpression of either of these proteins results in obesity. However the effect of exogenous Agrp and its in vivo interaction with alpha-melanocyte stimulating hormone (alphaMSH), the likely endogenous melanocortin 3 and 4 receptor (MC3-R and MC4-R) agonist, have not been demonstrated. We report that 1 nmol of Agrp(83-132), a C-terminal fragment of Agrp, when administered intracerebroventricularly (ICV) into rats, increased food intake over a 24-h period (23.0+/-1.4 g saline vs 32.9+/-2.3 g Agrp, pinhibition of cAMP activation to that previously reported for the full length peptide. In conclusion, Agrp(83-132) administered i.c.v. increases feeding with long lasting effects and is able to inhibit the action of alphaMSH. This interaction may be mediated by the MC3-R and/or MC4-R.

  9. I111n-Labeled Cystine-Knot Peptides Based on the Agouti-Related Protein for Targeting Tumor Angiogenesis

    Directory of Open Access Journals (Sweden)

    Lei Jiang

    2012-01-01

    Full Text Available Agouti-related protein (AgRP is a 4-kDa cystine-knot peptide of human origin with four disulfide bonds and four solvent-exposed loops. The cell adhesion receptor integrin αvβ3 is an important tumor angiogenesis factor that determines the invasiveness and metastatic ability of many malignant tumors. AgRP mutants have been engineered to bind to integrin αvβ3 with high affinity and specificity using directed evolution. Here, AgRP mutants 7C and 6E were radiolabeled with 111In and evaluated for in vivo targeting of tumor integrin αvβ3 receptors. AgRP peptides were conjugated to the metal chelator 1, 4, 7, 10-tetra-azacyclododecane- N, N′, N″, N‴-tetraacetic acid (DOTA and radiolabeled with 111In. The stability of the radiopeptides 111In-DOTA-AgRP-7C and 111In-DOTA-AgRP-6E was tested in phosphate-buffered saline (PBS and mouse serum, respectively. Cell uptake assays of the radiolabeled peptides were performed in U87MG cell lines. Biodistribution studies were performed to evaluate the in vivo performance of the two resulting probes using mice bearing integrin-expressing U87MG xenograft tumors. Both AgRP peptides were easily labeled with 111In in high yield and radiochemical purity (>99%. The two probes exhibited high stability in phosphate-buffered saline and mouse serum. Compared with 111In-DOTA-AgRP-6E, 111In-DOTA-AgRP-7C showed increased U87MG tumor uptake and longer tumor retention (5.74±1.60 and 1.29±0.02%ID/g at 0.5 and 24 h, resp., which was consistent with measurements of cell uptake. Moreover, the tumor uptake of 111In-DOTA-AgRP-7C was specifically inhibited by coinjection with an excess of the integrin-binding peptidomimetic c(RGDyK. Thus, 111In-DOTA-AgRP-7C is a promising probe for targeting integrin αvβ3 positive tumors in living subjects.

  10. Agouti revisited: transcript quantification of the ASIP gene in bovine tissues related to protein expression and localization.

    Directory of Open Access Journals (Sweden)

    Elke Albrecht

    Full Text Available Beside its role in melanogenesis, the agouti signaling protein (ASIP has been related to obesity. The potentially crucial role in adipocyte development makes it a tempting candidate for economic relevant, fat related traits in farm animals. The objective of our study was to characterize the mRNA expression of different ASIP transcripts and of putative targets in different bovine tissues, as well as to study consequences on protein abundance and localization. ASIP mRNA abundance was determined by RT-qPCR in adipose and further tissues of cattle representing different breeds and crosses. ASIP mRNA was up-regulated more than 9-fold in intramuscular fat of Japanese Black cattle compared to Holstein (p<0.001. Further analyses revealed that a transposon-derived transcript was solely responsible for the increased ASIP mRNA abundance. This transcript was observed in single individuals of different breeds indicating a wide spread occurrence of this insertion at the ASIP locus in cattle. The protein was detected in different adipose tissues, skin, lung and liver, but not in skeletal muscle by Western blot with a bovine-specific ASIP antibody. However, the protein abundance was not related to the observed ASIP mRNA over-expression. Immuno-histochemical analyses revealed a putative nuclear localization of ASIP additionally to the expected cytosolic signal in different cell types. The expression of melanocortin receptors (MCR 1 to 5 as potential targets for ASIP was analyzed by RT-PCR in subcutaneous fat. Only MC1R and MC4R were detected indicating a similar receptor expression like in human adipose tissue. Our results provide evidence for a widespread expression of ASIP in bovine tissues at mRNA and, for the first time, at protein level. ASIP protein is detectable in adipocytes as well as in further cells of adipose tissue. We generated a basis for a more detailed investigation of ASIP function in peripheral tissues of various mammalian species.

  11. BAC Recombineering of the Agouti Loci from Spotted Gar and Zebrafish Reveals the Evolutionary Ancestry of Dorsal-Ventral Pigment Asymmetry in Fish.

    Science.gov (United States)

    Cal, Laura; MegÍas, Manuel; Cerdá-Reverter, José Miguel; Postlethwait, John H; Braasch, Ingo; Rotllant, Josep

    2017-11-01

    Dorsoventral pigment patterning, characterized by a light ventrum and a dark dorsum, is one of the most widespread chromatic adaptations in vertebrate body coloration. In mammals, this countershading depends on differential expression of agouti-signaling protein (ASIP), which drives a switch of synthesis of one type of melanin to another within melanocytes. Teleost fish share countershading, but the pattern results from a differential distribution of multiple types of chromatophores, with black-brown melanophores most abundant in the dorsal body and reflective iridophores most abundant in the ventral body. We previously showed that Asip1 (a fish ortholog of mammalian ASIP) plays a role in patterning melanophores. This observation leads to the surprising hypothesis that agouti may control an evolutionarily conserved pigment pattern by regulating different mechanisms in mammals and fish. To test this hypothesis, we compared two ray-finned fishes: the teleost zebrafish and the nonteleost spotted gar (Lepisosteus oculatus). By examining the endogenous pattern of asip1 expression in gar, we demonstrate a dorsoventral-graded distribution of asip1 expression that is highest ventrally, similar to teleosts. Additionally, in the first reported experiments to generate zebrafish transgenic lines carrying a bacterial artificial chromosome (BAC) from spotted gar, we show that both transgenic zebrafish lines embryos replicate the endogenous asip1 expression pattern in adult zebrafish, showing that BAC transgenes from both species contain all of the regulatory elements required for regular asip1 expression within adult ray-finned fishes. These experiments provide evidence that the mechanism leading to an environmentally important pigment pattern was likely in place before the origin of teleosts. © 2017 Wiley Periodicals, Inc.

  12. Fenproporex N-dealkylation to amphetamine--enantioselective in vitro studies in human liver microsomes as well as enantioselective in vivo studies in Wistar and Dark Agouti rats.

    Science.gov (United States)

    Kraemer, Thomas; Pflugmann, Thomas; Bossmann, Michael; Kneller, Nicole M; Peters, Frank T; Paul, Liane D; Springer, Dietmar; Staack, Roland F; Maurer, Hans H

    2004-09-01

    Fenproporex (FP) is known to be N-dealkylated to R(-)-amphetamine (AM) and S(+)-amphetamine. Involvement of the polymorphic cytochrome P450 (CYP) isoform CYP2D6 in metabolism of such amphetamine precursors is discussed controversially in literature. In this study, the human hepatic CYPs involved in FP dealkylation were identified using recombinant CYPs and human liver microsomes (HLM). These studies revealed that not only CYP2D6 but also CYP1A2, CYP2B6 and CYP3A4 catalyzed this metabolic reaction for both enantiomers with slight preference for the S(+)-enantiomer. Formation of amphetamine was not significantly changed by quinidine and was not different in poor metabolizer HLM compared to pooled HLM. As in vivo experiments, blood levels of R(-)-amphetamine and S(+)-amphetamine formed after administration of FP were determined in female Dark Agouti rats (fDA), a model of the human CYP2D6 poor metabolizer phenotype (PM), male Dark Agouti rats (mDA), an intermediate model, and in male Wistar rats (WI), a model of the human CYP2D6 extensive metabolizer phenotype. Analysis of the plasma samples showed that fDA exhibited significantly higher plasma levels of both amphetamine enantiomers compared to those of WI. Corresponding plasma levels in mDA were between those in fDA and WI. Furthermore, pretreatment of WI with the CYP2D inhibitor quinine resulted in significantly higher amphetamine plasma levels, which did not significantly differ from those in fDA. The in vivo studies suggested that CYP2D6 is not crucial to the N-dealkylation but to another metabolic step, most probably to the ring hydroxylation. Further studies are necessary for elucidating the role of CYP2D6 in FP hydroxylation.

  13. Variaciones nucleotídicas de dos grupos de tepezcuintles, Agouti paca (Rodentia: Agoutidae, en cautiverio provenientes de dos localidades de Yucatán, México

    Directory of Open Access Journals (Sweden)

    Rubén C Montes-Pérez

    2006-09-01

    Full Text Available Estimamos las variaciones nucleotídicas entre dos grupos de tepezcuintles (Agouti paca provenientes de los estados de Campeche y Quintana Roo, México y, dentro de cada grupo. Se colectaron muestras sanguíneas de once A. paca mantenidos en cautiverio. El ADN de leucocitos se utilizó para efectuar la amplificación aleatoria de polimorfismos de ADN (RAPD. Se seleccionaron los iniciadores número tres 5’ -d(GTAGACCCGT-3’ y seis 5’ -d(CCCGTCAGCA-3’ del estuche (Ready.To.Go. RAPD Analysis Beads, Amersham Pharmacia Biotech, porque produjeron un adecuado número de bandas. Los patrones electroforéticos de bandas fueron procesados con el software para análisis filogenético basado en el método de UPGMA para estimar la variación nucleotídica. El árbol filogenético obtenido con el iniciador tres reveló una agrupación dicotómica entre los animales de ambos estados de la Península de Yucatán, con un valor de divergencia de 1.983 nucleótidos de cada cien. Los animales de Quintana Roo mostraron un agrupamiento con el iniciador seis y, otro grupo más con animales procedentes de Campeche. La variación nucleotídica entre estos dos grupos fue de 2.118 nucleótidos por cada cien. Las variaciones nucleotídicas dentro de los grupos procedentes de ambos estados, para los dos iniciadores, mostraron valores que fluctuaron entre 0.46 y 1.68 nucleótidos de cada cien, lo cual indica que la variación nucleotídica entre los dos grupos de animales es alrededor de dos nucleótidos por cada cien y, dentro de grupos es menor a 1.7 nucleótidos por cada cien.Nucleotidic variations of two captive groups of tepezcuintle, Agouti paca (Rodentia: Agoutidae, from two sites in Yucatan, Mexico. The objective of this work was to estimate the nucleotidic variation between two groups of tepezcuintles (Agouti paca from the states of Campeche and Quintana Roo, Mexico and within members of each group. Blood samples were collected from eleven A. paca kept in

  14. Leishmaniose cutânea na Amazônia: isolamento de Leishmania (Viannia lainsoni do roedor Agouti paca (Rodentia: Dasyproctidae, no estado do Pará, Brasil Cutaneous leishmaniasis in the Amazon Region: isolation of Leishmania (Viannia lainsoni from the rodent Agouti paca (Rodentia: Dasyproctidae in Pará State, Brazil

    Directory of Open Access Journals (Sweden)

    Fernando T. Silveira

    1991-02-01

    Full Text Available Fez-se o registro, pela primeira vez, do isolamento de Leishmania (V. lainsoni de um mamífero silvestre, o roedor Agouti paca (Rodentia: Dasyproctidae, no Estado do Pará, Brasil. As amostras do parasita foram isoladas da pele, aparentemente íntegra, de 3 espécimes desse roedor, capturados no município de Tucuruí (ilha de Tocantins, em área que seria inundada pela formação do lago da hidrelétrica construída naquele município. Nenhum isolamento foi obtido de vísceras de qualquer dos animais. A identificação das amostras de L. (V. lainsoni baseou-se na morfologia de amastigotas e promastigotas, no comportamento da infecção em "hamsters", na análise bioquímica de isoenzimas e, ainda, através de testes com anticorpos monoclonais. A natureza inaparente da infecção nos animais faz supor que o mamífero em questão possa representar um hospedeiro definitivo do parasita na região Amazônica.The isolation of Leishmania (V. lainsoni is recorded for the first time from a wild animal, the rodent Agouti paca (Rodentia: Dasyproctidae, from Pará State, north Brazil. Isolates of the parasite were made from apparently normal skin of 3 specimens of this rodent captured on the Island of Tocantins, in the municipality of Tucuruí, an area subsequently flooded in the formation of the lake associated with the Tucuruí hydroeletric dam. No isolations were made from the viscera. Identification of the parasite was in each case based on morphology of the amastigotes and promastigotes, behavior of the organism in hamsters, isoenzymes profiles and the use of monoclonal antibodies. The inapparent nature of the infection leads us to suggest that the "paca", Agouti paca, represents a primitive host of L. (V. lainsoni in the Amazon Region.

  15. Effects of prophylactic and therapeutic teriflunomide in transcranial magnetic stimulation-induced motor-evoked potentials in the dark agouti rat model of experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Iglesias-Bregna, Deborah; Hanak, Susan; Ji, Zhongqi; Petty, Margaret; Liu, Li; Zhang, Donghui; McMonagle-Strucko, Kathleen

    2013-10-01

    Teriflunomide is a once-daily oral immunomodulatory agent recently approved in the United States for the treatment of relapsing multiple sclerosis (RMS). This study investigated neurophysiological deficits in descending spinal cord motor tracts during experimental autoimmune encephalomyelitis (EAE; a model of multiple sclerosis) and the functional effectiveness of prophylactic or therapeutic teriflunomide treatment in preventing the debilitating paralysis observed in this model. Relapsing-remitting EAE was induced in Dark Agouti rats using rat spinal cord homogenate. Animals were treated with oral teriflunomide (10 mg/kg daily) prophylactically, therapeutically, or with vehicle (control). Transcranial magnetic motor-evoked potentials were measured throughout the disease to provide quantitative assessment of the neurophysiological status of descending motor tracts. Axonal damage was quantified histologically by silver staining. Both prophylactic and therapeutic teriflunomide treatment significantly reduced maximum EAE disease scores (P teriflunomide treatment regimens prevented a delay in wave-form latency and a decrease in wave-form amplitude compared with that observed in vehicle-treated animals. A significant reduction in axonal loss was observed with both teriflunomide treatment regimens compared with vehicle (P teriflunomide can prevent the deficits observed in this animal model in descending spinal cord motor tracts. The mechanism behind reduced axonal loss and improved motor function may be primarily the reduced inflammation and consequent demyelination observed in these animals through the known effects of teriflunomide on impairing proliferation of stimulated T cells. These findings may have significant implications for patients with RMS.

  16. Plasma agouti-related protein (AGRP), growth hormone, insulin responses to a single circuit-resistance exercise in male college students.

    Science.gov (United States)

    Ghanbari-Niaki, Abbass; Nabatchian, Saeid; Hedayati, Mehdi

    2007-05-01

    The ability of acute exercise to stimulate appetite and food intake depends on intensity, duration, and agouti-related protein (AGRP) levels. Fasting, as well as any negative energy balance, has been reported to increase AGRP expression in the arcuate nucleus (ARC) of the hypothalamus and other extra-hypothalamic tissues in human and rats. The purpose of the present study was to investigate the response of plasma AGRP, GH and insulin to a single circuit-resistance exercise. Twenty volunteer male college students completed a single bout of circuit-resistance training (10 exercises at 35% of 1RM). Blood samples were collected before, immediately and 30 min following the exercise protocol. Plasma AGRP and GH levels showed a significant increase immediately after exercise and returned to pre exercise values during the recovery period. The data indicate that exercise protocol was able to increase plasma AGRP and GH levels. A higher plasma AGRP level might result in an acute exercise-induced hyperphagia and help to fuel post-exercise restoration processes.

  17. Expression of neuropeptide Y and agouti-related peptide in the hypothalamic arcuate nucleus of newborn neurogenin3 null mutant mice.

    Science.gov (United States)

    Arai, Yuta; Gradwohl, Gérard; Kameda, Yoko

    2010-04-01

    Mice deficient in neurogenin 3 (Ngn3) fail to generate pancreatic endocrine cells and intestinal endocrine cells. Hypothalamic neuropeptides implicated in the control of energy homeostasis might also be affected in Ngn3 homozygous null mutant mice. We investigated the expression of two prominent orexigenic neuropeptides, neuropeptide Y (NPY) and agouti-related protein (AgRP), in the hypothalamic arcuate nucleus of newborn wild-type and Ngn3 null mutant mice. Immunohistochemical analysis demonstrated that, in Ngn3 null mutants, the number of NPY-immunoreactive neurons and nerve fibers was markedly increased in the arcuate nucleus, and the nerve fibers were widely distributed in the hypothalamic area, including the paraventricular and dorsomedial nuclei. Little increase of AgRP immunoreactivity was detected in the arcuate nucleus of mutant mice. In situ hybridization analysis confirmed the increased population of the NPY neurons in the arcuate nucleus of the mutants. The NPY mRNA level, as estimated by laser capture microdissection and real-time quantitative polymerase chain reaction, was 371% higher in Ngn3 null mutants than in wild-type mice. AgRP mRNA levels did not differ significantly between the null mutants and wild-type mice. Thus, up-regulation of the hypothalamic NPY system is probably a feature characteristic of Ngn3 null mice.

  18. Defining MC1R regulation in human melanocytes by its agonist α-melanocortin and antagonists agouti signaling protein and β-defensin 3.

    Science.gov (United States)

    Swope, Viki B; Jameson, Joshua A; McFarland, Kevin L; Supp, Dorothy M; Miller, William E; McGraw, Dennis W; Patel, Mira A; Nix, Matthew A; Millhauser, Glenn L; Babcock, George F; Abdel-Malek, Zalfa A

    2012-09-01

    The melanocortin 1 receptor (MC1R), a G(s) protein-coupled receptor, has an important role in human pigmentation. We investigated the regulation of expression and activity of the MC1R in primary human melanocyte cultures. Human β-defensin 3 (HBD3) acted as an antagonist for MC1R, inhibiting the α-melanocortin (α-melanocyte-stimulating hormone (α-MSH))-induced increase in the activities of adenylate cyclase and tyrosinase, the rate-limiting enzyme for melanogenesis. α-Melanocortin and forskolin, which activate adenylate cyclase, and 12-O-tetradecanoylphorbol-13-acetate, which activates protein kinase C, increased, whereas exposure to UV radiation reduced, MC1R gene and membrane protein expression. Brief treatment with α-MSH resulted in MC1R desensitization, whereas continuous treatment up to 3 hours caused a steady rise in cAMP, suggesting receptor recycling. Pretreatment with agouti signaling protein or HBD3 prohibited responsiveness to α-MSH, but not forskolin, suggesting receptor desensitization by these antagonists. Melanocytes from different donors expressed different levels of the G protein-coupled receptor kinases (GRKs) 2, 3, 5, and 6, as well as β-arrestin 1. Therefore, in addition to the MC1R genotype, regulation of MC1R expression and activity is expected to affect human pigmentation and the responses to UV.

  19. Distinct Roles for JNK and IKK Activation in Agouti-Related Peptide Neurons in the Development of Obesity and Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Eva Tsaousidou

    2014-11-01

    Full Text Available Activation of c-Jun N-terminal kinase 1 (JNK1- and inhibitor of nuclear factor kappa-B kinase 2 (IKK2-dependent signaling plays a crucial role in the development of obesity-associated insulin and leptin resistance not only in peripheral tissues but also in the CNS. Here, we demonstrate that constitutive JNK activation in agouti-related peptide (AgRP-expressing neurons of the hypothalamus is sufficient to induce weight gain and adiposity in mice as a consequence of hyperphagia. JNK activation increases spontaneous action potential firing of AgRP cells and causes both neuronal and systemic leptin resistance. Similarly, activation of IKK2 signaling in AgRP neurons also increases firing of these cells but fails to cause obesity and leptin resistance. In contrast to JNK activation, IKK2 activation blunts insulin signaling in AgRP neurons and impairs systemic glucose homeostasis. Collectively, these experiments reveal both overlapping and nonredundant effects of JNK- and IKK-dependent signaling in AgRP neurons, which cooperate in the manifestation of the metabolic syndrome.

  20. UN ÍNDICE PARA LA EVALUACIÓN DEL HÁBITAT DE AGOUTI TACZANOWSK/1 (RODENTIA: AGOUTIDAE EN ÁREAS DE BOSQUE ANDINO NUBLADO

    Directory of Open Access Journals (Sweden)

    Jairo Pérez-Torres

    2002-06-01

    Full Text Available Se presenta un índice que permitirá evaluar el hábitat de la "Lapa andiim" o "Tinajo" (Agouti taczanowskii en zonas de bosque andino nublado. El objetivo fundamental de este índice, es obtener elementos que sirvan para la toma de decisiones en cuanto al diseño de áreas de reserva y planes de manejo sobre esta especie. Este índice se basa en la aplicación de criterios tanto cualitativos como cuantitativos, los cuales son tabulados y computados para sacar un valor de calidad de hábitat para cada uno de los ambientes bajo estudio. Los valores del índice de diferentes áreas pueden ser comparados para determinar de manera jerárquica cuál es más adecuado para realizar actividades particulares de manejo o conservación de esta especie en zonas de bosque andino. El índice se basa en doce variables: porcentaje de uso del área, abundancia del "Tinajo", explotación humana, grado de protección, riqueza en la dieta, cobertura foliar de las especies vegetales, accesibilidad a las especies vegetales que hacen parte de la dieta, heterogeneidad del hábitat, disponibilidad de agua, áreas potenciales de reproducción, presencia de predadores y factores antrópicos.

  1. Central administration of ghrelin and agouti-related protein (83-132) increases food intake and decreases spontaneous locomotor activity in rats.

    Science.gov (United States)

    Tang-Christensen, Mads; Vrang, Niels; Ortmann, Sylvia; Bidlingmaier, Martin; Horvath, Tamas L; Tschöp, Matthias

    2004-10-01

    Ghrelin was recently identified as an endogenous ligand of the GH secretagogue receptor. The novel peptide hormone is produced by gastric A-like cells, and circulating levels rise before feeding, suggestive of ghrelin as an endogenous hunger factor. ghrelin stimulates food intake and promotes adiposity after peripheral or central administration, likely by activating hypothalamic neurons expressing the orexigenic neuropeptides neuropeptide Y (NPY) and agouti-related protein (AGRP). To examine whether ghrelin-induced feeding resembles NPY and AGRP [AGRP fragment (83-132)] induced orexia, we compared the short- and long-term orexigenic capacity of the three peptides. A single intracerebroventricular injection of ghrelin (0.2, 1.0, and 5.0 microg) increased food intake in a dose-dependent manner. A prolonged and uncompensated increase in feeding was seen after the highest dose of ghrelin. The prolonged effects on feeding (+72 h) closely resembled those of AGRP (83-132) but not NPY. Surprisingly, ghrelin injections reduced overall locomotor activity by 20% during the first 24-h observation period. AGRP (83-132) had similar effects on locomotor behavior, whereas NPY had no effect. In summary, ghrelin causes long-term increases of food intake and, like AGRP, plays a previously unknown role as a suppressor of spontaneous physical activity. Expanding the current model of food intake control to include mechanisms regulating physical activity may promote our understanding of two major etiological factors causing obesity.

  2. Negative correlation between neuropeptide Y/agouti-related protein concentration and adiponectinemia in nonalcoholic fatty liver disease obese adolescents submitted to a long-term interdisciplinary therapy.

    Science.gov (United States)

    de Piano, Aline; Tock, Lian; Carnier, June; Oyama, Lila M; Oller do Nascimento, Cláudia M; Martinz, Aniella C; Foschini, Denis; Sanches, Priscila L; Ernandes, Regina M Y; de Mello, Marco Túlio; Tufik, Sérgio; Dâmaso, Ana R

    2010-05-01

    The complexity pathogenesis in the nonalcoholic fatty liver disease (NAFLD) involves an interplay between adipokines and neuroendocrine regulation of energy balance, including the role of neuropeptide Y (NPY)/agouti-related protein (AgRP) system. The first aim of this study was to assess the effect of long-term interdisciplinary intervention on NAFLD in obese adolescents, and the second objective was to establish the relationship between NPY/AgRP ratio and adiponectinemia. Fifty-five postpuberty obese adolescents were submitted to interdisciplinary intervention. The group was divided between subjects with and without NAFLD (n = 19 and 36, respectively). Blood samples were collected to measure glycemia, hepatic transaminases, lipid profile, insulin resistance, and sensitivity. Adiponectin, NPY, and AgRP concentrations were measured by enzyme-linked immunosorbent assay. Food intake was measured using 3-day diet records. It was observed at baseline that important clinical parameters including body weight, body mass index, visceral fat, homeostasis model assessment of insulin resistance, quantitative insulin sensitivity check index, triglycerides, very low-density lipoprotein cholesterol, and hepatic transaminases were more altered in NAFLD patients. After the intervention, these parameters, total energy, and macronutrient intake were reduced significantly in both groups. The most important finding was the positive correlation between AgRP and visceral fat in all patients and the negative correlation between NPY/AgRP and adiponectinemia only in NAFLD obese adolescents. The NAFLD patients presented more altered clinical parameters than the non-NAFLD subjects, including the negative correlation between adiponectinemia and NPY/AgRP. These results suggested that NAFLD obese adolescents presented an inflammatory profile that can influence the neuroendocrine regulation of energy balance, suggesting an additional impairment in the weight loss therapy.

  3. Proliferation and Migration of Peripheral Retinal Pigment Epithelial Cells Are Associated with the Upregulation of Wingless-Related Integration and Bone Morphogenetic Protein Signaling in Dark Agouti Rats.

    Science.gov (United States)

    Al-Hussaini, Heba; Kilarkaje, Narayana; Shahabi, Golnaz; Al-Mulla, Fahad

    The aim of this study was to investigate the possible migration of proliferating peripheral retinal pigment epithelial (RPE) cells and their association with differential gene expressions. The RPE layer was obtained from the inner aspect of the eyeball of dark agouti rats (12-13 weeks old) and was mounted on glass slides. The peripheral RPE cell proliferation was evaluated using bromodeoxyuridine immunohistochemistry (n = 10). The cell migration was examined using the Dil tracer technique (n = 40) at the end of weeks 6, 10, 14 and 18. Affymetrix microarray analysis was used to investigate differential gene expressions in peripheral and central RPE cells, which was authenticated by RT-PCR using 4 RPE-specific genes (n = 10). In this study, peripheral RPE cells divided and appeared in clusters, but equatorial and central RPE cells rarely divided. The peripheral RPE cells migrated to the central RPE region in a time-dependent manner up to the end of week 14, but not later. The microarray analysis showed the expression of 9,645 out of a total of 35,220 genes studied. Among the 9,645 genes, 573 were differentially expressed (438 were upregulated and 135 were downregulated) in peripheral RPE cells as compared to central RPE cells. Of these 573 genes, 56 were associated with signaling pathways related to the regulation of cell proliferation, including Pax6, TGFβ, BMP and Wnt, and 404 were associated with pathways of cell migration. In this study, peripheral RPE cells divided and migrated to the central region. This process was associated with differential gene expressions in these cells. © 2016 S. Karger AG, Basel.

  4. Anorexigenic and Orexigenic Hormone Modulation of Mammalian Target of Rapamycin Complex 1 Activity and the Regulation of Hypothalamic Agouti-Related Protein mRNA Expression

    Directory of Open Access Journals (Sweden)

    Kenneth R. Watterson

    2012-03-01

    Full Text Available Activation of mammalian target of rapamycin 1 (mTORC1 by nutrients, insulin and leptin leads to appetite suppression (anorexia. Contrastingly, increased AMP-activated protein kinase (AMPK activity by ghrelin promotes appetite (orexia. However, the interplay between these mechanisms remains poorly defined. The relationship between the anorexigenic hormones, insulin and leptin, and the orexigenic hormone, ghrelin, on mTORC1 signalling was examined using S6 kinase phosphorylation as a marker for changes in mTORC1 activity in mouse hypothalamic GT1-7 cells. Additionally, the contribution of AMPK and mTORC1 signalling in relation to insulin-, leptin- and ghrelin-driven alterations to mouse hypothalamic agouti-related protein (AgRP mRNA levels was examined. Insulin and leptin increase mTORC1 activity in a phosphoinositide-3-kinase (PI3K- and protein kinase B (PKB-dependent manner, compared to vehicle controls, whereas increasing AMPK activity inhibits mTORC1 activity and blocks the actions of the anorexigenic hormones. Ghrelin mediates an AMPK-dependent decrease in mTORC1 activity and increases hypothalamic AgRP mRNA levels, the latter effect being prevented by insulin in an mTORC1-dependent manner. In conclusion, mTORC1 acts as an integration node in hypothalamic neurons for hormone-derived PI3K and AMPK signalling and mediates at least part of the assimilated output of anorexigenic and orexigenic hormone actions in the hypothalamus.

  5. Ghrelin receptors mediate ghrelin-induced excitation of agouti-related protein/neuropeptide Y but not pro-opiomelanocortin neurons.

    Science.gov (United States)

    Chen, Shao-Rui; Chen, Hong; Zhou, Jing-Jing; Pradhan, Geetali; Sun, Yuxiang; Pan, Hui-Lin; Li, De-Pei

    2017-08-01

    Ghrelin increases food intake and body weight by stimulating orexigenic agouti-related protein (AgRP)/neuropeptide Y (NPY) neurons and inhibiting anorexic pro-opiomelanocortin (POMC) neurons in the hypothalamus. Growth hormone secretagogue receptor (Ghsr) mediates the effect of ghrelin on feeding behavior and energy homeostasis. However, the role of Ghsr in the ghrelin effect on these two populations of neurons is unclear. We hypothesized that Ghsr mediates the effect of ghrelin on AgRP and POMC neurons. In this study, we determined whether Ghsr similarly mediates the effects of ghrelin on AgRP/NPY and POMC neurons using cell type-specific Ghsr-knockout mice. Perforated whole-cell recordings were performed on green fluorescent protein-tagged AgRP/NPY and POMC neurons in the arcuate nucleus in hypothalamic slices. In Ghsr +/+ mice, ghrelin (100 nM) significantly increased the firing activity of AgRP/NPY neurons but inhibited the firing activity of POMC neurons. In Ghsr -/- mice, the excitatory effect of ghrelin on AgRP/NPY neurons was abolished. Ablation of Ghsr also eliminated ghrelin-induced increases in the frequency of GABAergic inhibitory postsynaptic currents of POMC neurons. Strikingly, ablation of Ghsr converted the ghrelin effect on POMC neurons from inhibition to excitation. Des-acylated ghrelin had no such effect on POMC neurons in Ghsr -/- mice. In both Ghsr +/+ and Ghsr -/- mice, blocking GABA A receptors with gabazine increased the basal firing activity of POMC neurons, and ghrelin further increased the firing activity of POMC neurons in the presence of gabazine. Our findings provide unequivocal evidence that Ghsr is essential for ghrelin-induced excitation of AgRP/NPY neurons. However, ghrelin excites POMC neurons through an unidentified mechanism that is distinct from conventional Ghsr. © 2017 International Society for Neurochemistry.

  6. New records for helminths of hystricognath rodents from the middle and high Rio Negro microregion, State of Amazonas, Brazil Novos registros para helmintos de roedores histricognatos da microrregião do médio e alto Rio Negro, Estado do Amazonas, Brasil

    Directory of Open Access Journals (Sweden)

    Alessandra Q. Gonçalves

    2006-09-01

    Full Text Available Four nematodes and one cestode species from three Brazilian agoutis - two Dasyprocta fuliginosa Wagler, 1832 and one Dasyprocta leporina (Linnaeus, 1758 - and six pacas - Agouti paca (Linnaeus, 1766 - captured in tributaries rivers in the middle and high Rio Negro microregion, State of Amazonas, Brazil, were studied. The nematodes Physaloptera torresi (Travassos, 1920 Ortlepp, 1922, Physocephalus mediospiralis (Molin, 1859 Hall, 1916 and the cestode Raillietina (R. trinitatae (Cameron & Reesal, 1951 Baer & Sandars, 1956 are reported from the State of Amazonas for the first time. The studied helminths (the nematodes P. torresi, P. mediospiralis, Trichuris gracilis (Rud., 1819 Hall, 1916, Helminthoxys urichi (Cameron & Reesal, 1951 Hugot, 1986 and the cestode R. (R. trinitatae represent new host record for Dasyprocta fuliginosa. New morphometric data and remarks about each species are provided.Foram estudadas quatro espécies de nematóides e uma de cestóide coletados de três cutias - duas Dasyprocta fuliginosa Wagler, 1832 e uma Dasyprocta leporina (Linnaeus, 1758 - e seis pacas - Agouti paca (Linnaeus, 1766 - capturadas em rios afluentes na microrregião do médio e alto Rio Negro, Estado do Amazonas, Brasil. Os nematóides Physaloptera torresi (Travassos, 1920 Ortlepp, 1922, Physocephalus mediospiralis (Molin, 1859 Hall, 1916 e o cestóide Raillietina (R. trinitatae (Cameron & Reesal, 1951 Baer & Sandars, 1956 são registrados pela primeira vez no Estado do Amazonas. Os helmintos estudados (os nematóides P. torresi, P. mediospiralis, Trichuris gracilis (Rud., 1819 Hall, 1916, Helminthoxys urichi (Cameron & Reesal, 1951 Hugot, 1986 e o cestóide R. (R. trinitatae representam novos registros para Dasyprocta fuliginosa. Novos dados morfométricos e observações sobre cada espécie são fornecidos.

  7. Seguimiento anual de la parasitosis gastrointestinal del tepezcuintle, Agouti paca (Rodentia: Agoutidae en cautiverio en el trópico mexicano

    Directory of Open Access Journals (Sweden)

    Oscar Ramírez-Herrera

    2001-12-01

    Full Text Available Informes previos muestran que el tepezcuintle es comúnmente infestado por parásitos gastrointestinales (PGI, principalmente por Eucoccidiida y helmintos; sin embargo, no existe información disponible sobre la frecuencia de estos parásitos y su excreción de huevecillos en heces en diferentes momentos a lo largo de un año. Esta información puede proveer un fundamento valioso para el establecimiento de estrategias de control contra PGI en tepezcuintles en cautiverio. Los objetivos del presente trabajo fueron determinar la prevalencia de los géneros y órdenes de PGI que infestan al tepezcuintle en cautiverio y describir la dinámica de excreción de huevecillos y ooquistes fecales en un año. Diez tepezcuintles fueron muestreados (heces dos veces por mes durante 12 meses. Las muestras fecales se procesaron por las técnicas de Flotación centrifugada y McMaster. Se determinaron dos órdenes: Strongylida y Eucoccidiida y dos géneros Strongyloides y Trichuris. Las prevalencias de huevecillos del orden Strongylida, ooquistes de Eucoccidiida y huevecillos de Trichuris sp. en los animales fue de 10 al 20 % en ciertos meses del año. El género Strongyloides fue el más importante, encontrándose de 60 a 100 % de los animales durante todo el año. La excreción promedio de huevecillos en el grupo estudiado fue de 45 a 372 huevecillos por gramo de heces. Los tepezcuintles en cautiverio en Yucatán están parasitados por Strongyloides sp. durante todo el año. Ocasionalmente estos animales tienen ooquistes de Eucoccidiida y huevecillos de Strongylida y Trichuris spPrevious reports showed that the tepezcuintle (Agouti paca is commonly infested by gastrointestinal parasites (GIP, mainly Eucoccidiida and helminths. However, there is no available information on the frequency of those parasites and their faecal egg excretions at different moments during the year. These information would provide a valuable baseline for the establishment of control

  8. Comparison of the disposition behavior of organic anions in an animal model for Wilson's disease (Long-Evans Cinnamon rats) with that in normal Long-Evans Agouti rats.

    Science.gov (United States)

    Itagaki, Shirou; Sugawara, Mitsuru; Kobayashi, Michiya; Miyazaki, Katsumi; Hirano, Takeshi; Iseki, Ken

    2004-04-01

    Long-Evans Cinnamon (LEC) rats have an abnormality similar to that observed in Wilson's disease in humans and are therefore a good animal model for the study of Wilson's disease. LEC rats develop hereditary hepatitis and severe jaundice. Mutant animals with hyperbilirubinemia have been widely used as animal models for human diseases. Among these mutant animals, Eisai hyperbilirubinemic rats (EHBR) have defective biliary excretion of organic anions. Thus, biliary excretion of sulfobromophthalein (BSP) and urinary excretion of phenolsulfonphthalein (PSP) in LEC rats were compared with those in Long-Evans Agouti (LEA) rats. In LEC rats, the excretion of BSP, a multidrug resistance-associated protein 2 (Mrp2/Abcc2) substrate, was significantly decreased compared to that in LEA rats. It has been reported that the transport function for organic anions on the kidney is maintained in EHBR. However, the urinary excretion of PSP is impaired in LEC rats. It is possible that organic anion transporters responsible for the urinary excretion of PSP in LEA rats and EHBR are impaired in LEC rats. It is important to elucidate the relationship between organic anion secretion and Wilson's disease.

  9. Genetic background (DDD/Sgn versus C57BL/6J) strongly influences postnatal growth of male mice carrying the A(y) allele at the agouti locus: identification of quantitative trait loci associated with diabetes and body weight loss.

    Science.gov (United States)

    Suto, Jun-ichi; Satou, Kunio

    2013-05-04

    Mice carrying the A(y) allele at the agouti locus become obese and are heavier than their non-A(y) littermates. However, this does not hold true for the genetic background of the DDD mouse strain. At 22 weeks of age, DDD.Cg-A(y) females are heavier than DDD females, whereas DDD.Cg-A(y) males are lighter than DDD males. This study aimed to determine the possible cause and identify the genes responsible for the lower body weight of DDD.Cg-A(y) males. Growth curves of DDD.Cg-A(y) mice were analyzed and compared with those of B6.Cg-A(y) mice from 5 to 25 weeks. In DDD.Cg-A(y) males, body weight gain stopped between 16 and 17 weeks and the body weight gradually decreased; thus, the lower body weight was a consequence of body weight loss. Quantitative trait locus (QTL) mapping was performed in backcrossed (BC) males of DDD × (B6 × DDD.Cg-A(y)) F(1)-A(y) mice. For the body weight at 25 weeks, significant QTLs were identified on chromosomes 1 and 4. The DDD allele was associated with a lower body weight at both loci. In particular, the QTL on chromosome 4 interacted with the A(y) allele. Furthermore, suggestive QTLs for plasma glucose and high molecular weight adiponectin levels were coincidentally mapped to chromosome 4. The DDD allele was associated with increased glucose and decreased adiponectin levels. When the body weight at 25 weeks and plasma glucose levels were considered as dependent and independent variables, respectively, BC A(y) males were classified into two groups according to statistical analysis using the partition method. Mice of one group had significantly higher glucose and lower adiponectin levels than those of the other group and exhibited body weight loss as observed with DDD-A(y) males. The lower body weight of DDD.Cg-A(y) male mice was a consequence of body weight loss. Diabetes mellitus has been suggested to be a possible contributory factor causing body weight loss. The QTL on distal chromosome 4 contained the major responsible genes. This QTL

  10. Genetic background (DDD/Sgn versus C57BL/6J) strongly influences postnatal growth of male mice carrying the Ay allele at the agouti locus: identification of quantitative trait loci associated with diabetes and body weight loss

    Science.gov (United States)

    2013-01-01

    Background Mice carrying the Ay allele at the agouti locus become obese and are heavier than their non-Ay littermates. However, this does not hold true for the genetic background of the DDD mouse strain. At 22 weeks of age, DDD.Cg-Ay females are heavier than DDD females, whereas DDD.Cg-Ay males are lighter than DDD males. This study aimed to determine the possible cause and identify the genes responsible for the lower body weight of DDD.Cg-Ay males. Results Growth curves of DDD.Cg-Ay mice were analyzed and compared with those of B6.Cg-Ay mice from 5 to 25 weeks. In DDD.Cg-Ay males, body weight gain stopped between 16 and 17 weeks and the body weight gradually decreased; thus, the lower body weight was a consequence of body weight loss. Quantitative trait locus (QTL) mapping was performed in backcrossed (BC) males of DDD × (B6 × DDD.Cg-Ay) F1-Ay mice. For the body weight at 25 weeks, significant QTLs were identified on chromosomes 1 and 4. The DDD allele was associated with a lower body weight at both loci. In particular, the QTL on chromosome 4 interacted with the Ay allele. Furthermore, suggestive QTLs for plasma glucose and high molecular weight adiponectin levels were coincidentally mapped to chromosome 4. The DDD allele was associated with increased glucose and decreased adiponectin levels. When the body weight at 25 weeks and plasma glucose levels were considered as dependent and independent variables, respectively, BC Ay males were classified into two groups according to statistical analysis using the partition method. Mice of one group had significantly higher glucose and lower adiponectin levels than those of the other group and exhibited body weight loss as observed with DDD-Ay males. Conclusions The lower body weight of DDD.Cg-Ay male mice was a consequence of body weight loss. Diabetes mellitus has been suggested to be a possible contributory factor causing body weight loss. The QTL on distal chromosome 4 contained the major responsible genes

  11. Serological survey for Leishmania sp. infection in wild animals from the municipality of Maringá, Paraná state, Brazil

    Directory of Open Access Journals (Sweden)

    EM Voltarelli

    2009-01-01

    Full Text Available Leishmania sp. infection was investigated in wild animals from the Ingá Park, in the municipality of Maringá, Paraná state, Brazil, where American cutaneous leishmaniasis (ACL is an endemic disease. Sixty-five mammals, comprising Didelphis albiventris, Cerdocyon thous, Lycalopex vetulus, Cebus apella, Dasyprocta azarae, Dasypus novemcinctus, Procyon cancrivorus and Nasua nasua, were captured. Blood samples were collected for parasite cultivation. Antibodies were investigated by direct agglutination test (DAT using Leishmania (Viannia braziliensis as antigen. Flagellates were observed in blood cultures of 14 (35.9% Didelphis albiventris. Anti-Leishmania antibodies were detected in 31 (51.6% specimens of Cerdocyon thous, Lycalopex vetulus, Cebus apella, Dasyprocta azarae, Procyon cancrivorus and Nasua nasua. These results suggest that Cerdocyon thous and Lycalopex vetulus (crab-eating fox, Cebus apella (capuchin monkey, Dasyprocta azarae (agouti, Procyon cancrivorus (crab-eating raccoon and Nasua nasua (coati play an important role in the ACL transmission cycle in the northwestern region of Paraná, Brazil.

  12. Agouti-related protein prevents self-starvation

    NARCIS (Netherlands)

    Kas, M.J.H.; van Dijk, G; Scheurink, AJW; Adan, RAH

    2003-01-01

    Food restriction leads to a paradoxical increase in physical activity and further suppression of food intake, such as observed in anorexia nervosa.(1,2) To understand this pathophysiological process, we induced physical hyperactivity and self-starvation in rats by restricting food in the presence of

  13. Light microscope observations on the epididymis of paca (Agouti paca).

    Science.gov (United States)

    Schimming, Bruno Cesar; Machado, Márcia Rita Fernandes; Simões, Karina; da Cruz, Claudinei; Domeniconi, Raquel Fantin

    2013-01-01

    The features of paca epididymis, based on its appearance in light microscope, is described in this paper. The cellular population of the epithelial lining comprises principal cells, basal cells, apical cells, narrows cells, and hallo cells. The epididymis is divided in five distinct and continuous regions, Zone I, or initial segment, and zone II, are both localized into the head. Zone III comprises the distal head and all the body. Zones IV and V are restricted to the tail, in the proximal and distal cauda epididymis respectively. Each zone can be readily distinguished on the basis of morphological characteristics. The height of epididymal epithelium is greater in zone I. There is a progressive increase in the diameter of the tubular lumen through the different areas, with the maximum in the zone V. The presence of a high epithelium, and the virtual absence of sperm in zone I suggest fast transit of spermatozoa in this region. Zone V comprises the distal tail, has smaller epithelial lining, greater luminal diameter, shorter stereocilia than the other zones, and contains spermatozoa packed inside the lumen, that characterizes this zone as a place of sperm storage. The findings are compared with other reports in rodents and other domestic animals, to contribute to the understanding of epididymal morphophysiology.

  14. Topografia do cone medular da paca (Agouti paca, Linnaeus - 1766

    Directory of Open Access Journals (Sweden)

    Alessandra Regina Freixo Scavone

    2007-12-01

    Full Text Available Objetivamos neste trabalho determinar a esqueletopia da terminação do cone medular da paca relacionando com as vértebras lombares e sacrais, visando assim estabelecer parâmetros morfométricos e topográficos do cone medular nesta espécie. Para tanto, procedemos à dissecação, mediante incisão, rebatimento da pele, da tela subcutânea e da musculatura da região dorsal à coluna vertebral, com posterior secção e remoção dos arcos vertebrais para melhor visualização da medula espinhal. Após a individualização do cone medular, registramos os aspectos anatômicos de interesse, enfatizando seu início (base e seu término (ápice em relação às vértebras, e a partir de então efetuamos suas medidas com o auxílio de paquímetro; visando documentar nossos achados, realizamos fotografias e esquemas dos espécimes estudados.

  15. Uniparidade em pacas criadas em cativeiro (Agouti paca, Linnaeus, 1766 Uniparity in pacas bred in captivity (Agouti paca, Linnaeus, 1766

    Directory of Open Access Journals (Sweden)

    F.S. Oliveira

    2007-04-01

    Full Text Available Durante quatro anos foram detectadas 25 prenhezes, em 13 diferentes pacas, por meio de ultra-sonografia. Após a detecção ultra-sonográfica, as fêmeas foram separadas em baias individuais para o nascimento dos filhotes e aí mantidas até o desmame. Houve nascimento de apenas um animal por parto, ressaltando a característica reprodutiva de uniparidade, o que sugere a tendência de nascimento de apenas um filhote por parto, nessa espécie.During four years 25 pregnancies were detected in 13 different pacas by means of ultrasonography at a wild animal section. After ultrasound detection, females were separated in individual sets for delivering and kept until weaning of newborns. Only one newborn by delivery occurred, remarking the reproductive characteristic of uniparity, what suggests the trend of only one newborn in each delivery.

  16. Morfologia e dinâmica testicular em cutias - Dasyprocta prymnolopha adultas

    Directory of Open Access Journals (Sweden)

    D.J.A. Menezes

    Full Text Available RESUMO Este trabalho objetivou apresentar a caracterização da morfologia do testículo de cutia (Dasyproctaprymnolopha macho, com o intuito de colaborar com o conhecimento da morfofisiologia reprodutiva da espécie. Foram utilizados testículos de 47 animais, com idade entre um e dois anos, pesos homogêneos (2,08 ± 0,23kg, oriundos do Núcleo de Estudos e Preservação de Animais Silvestres do Centro de Ciências Agrárias da Universidade Federal do Piauí. As estruturas foram dissecadas, descritas, e fragmentos foram processados para a microscopia de luz, sendo, posteriormente avaliada a atividade gonadal. Observou-se que os testículos são órgãos elipsoides alongados, podendo ser encontrados na região inguinal ou na cavidade abdominal, não apresentando um escroto bem delimitado. Verificou-se também parênquima com característica histológica padrão para o órgão em mamíferos, com a identificação de oito tipos de associações celulares, caracterizando os estádios do ciclo do epitélio seminífero, com menor e maior frequência dos estádios 3 e 5, respectivamente.

  17. Zygomycetes from herbivore dung in the ecological reserve of Dois Irmãos, Northeast Brazil

    Directory of Open Access Journals (Sweden)

    André Luiz Cabral Monteiro de Azevedo Santiago

    2011-03-01

    Full Text Available Thirty-eight taxa of Zygomycetes distributed in 15 genera were recorded from tapir (Tapirus terrestris, camel (Camelus bactrianus, horse (Equus caballus, deer (Cervus elaphus, agouti (Dasyprocta aguti, donkey (Equus asinus, llama (Llama glama and waterbuck (Kobus ellipsiprymnus dung collected at the Reserva Ecológica de Dois Irmãos located in Recife, State of Pernambuco, Northeast Brazil. The samples were collected on a monthly basis from June 2005 to May 2006, taken to the laboratory and incubated in moist chambers. Higher number of taxa was observed in the excrements of tapir, followed by deer and donkey. The highest number of species was detected for Mucor, followed by Pilobolus. Statistical analyses showed significant differences in richness of Zygomycetes taxa between the herbivore dung types. Differences of species composition, however, were weak. Seasonality influenced the Zygomycetes species composition but not its richness. Variations in taxa composition between ruminants and non-ruminants dung were non significant.

  18. Wild Rodents as Experimental Intermediate Hosts of Lagochilascaris minor Leiper, 1909

    Directory of Open Access Journals (Sweden)

    Julieta Machado Paçô

    1999-07-01

    Full Text Available A total of 25 specimens of Cavia porcellus (guinea pig, 5 Dasyprocta agouti (agouti, and 22 Calomys callosus (vesper mice were inoculated with infective eggs of Lagochilascaris minor. The inoculum was prepared with embryonated eggs and orally administered to each individual animal through an esophagus probe. In parallel, 100 specimens of Felis catus domesticus were individually fed with 55-70 nodules containing 3rd-stage larvae encysted in tissues of infected rodents. Animals were examined and necropsied at different time intervals. The migration and encystment of L3 larva was observed in viscera, skeletal muscle, adipose and subcutaneous tissues from all rodents. Adult worms localized at abscesses in the cervical region, rhino, and oropharynx were recovered from domestic cats inoculated with infected rodent tissues. Through this study we can conclude that: (1 wild rodents act as intermediate hosts, characterizing this ascarid heteroxenic cycle; (2 in natural conditions rodents could possibly act as either intermediate hosts or paratenic hosts of Lagochilascaris minor; (3 despite the occurrence of an auto-infecting cycle, in prime-infection of felines (definite hosts the cycle is only completed when intermediate hosts are provided; and (4 in the wild, rodents could serve as a source of infection for humans as they are frequently used as food in regions with the highest incidence of human lagochilascariasis.

  19. Morfologia dos órgãos genitais externos do macho de cutia (Dasyprocta aguti. Linnaeus, 1766

    Directory of Open Access Journals (Sweden)

    Danilo José Ayres de Menezes

    2003-01-01

    Full Text Available Foram utilizados vinte e três cutias (D. aguti, machos, adultos, adquiridos em criatórios científicos, legalmente licenciados pelo IBAMA, da Universidade Federal do Piauí - UFPI, Teresina, PI e da Escola Superior Agrícola de Mossoró - ESAM, Mossoró, RN, com o objetivo de descrever morfologicamente os órgãos genitais masculinos externos, abordando aspectos histológicos e macroscópicos destes órgãos. Foi realizada a dissecação dos órgãos genitais externos dos espécimes. Fragmentos foram coletados e submetidos ao processamento histológico de rotina para inclusão em parafina, os quais foram cortados e corados pelos métodos de H/E e Tricômico de Masson e observados em microscópio de luz. Os resultados mostraram que o pênis destes animais possui características do tipo fibrocavernoso, com grande quantidade de estruturas queratinizadas no seu ápice. No terço médio do pênis da cutia foi evidenciado uma flexura peniana em forma de "U" deitado; a glande do pênis encontra-se revestida por uma epiderme queratinizada contendo espículas córneas; um osso peniano substituindo o corpo cavernoso e um saco suburetral ventral, com dois longos esporões córneos no seu interior, estão presentes no pênis desses espécimes. Na região escrotal não se observa limites externos nítidos do escroto. Dorsalmente, abaixo da lâmina interna do prepúcio, próximo ao óstio prepucial, verifica-se um par de glândulas prepuciais.

  20. Agouti-related peptide plays a critical role in leptin's effects on female puberty and reproduction

    OpenAIRE

    Sheffer-Babila, Sharone; Sun, Yan; Israel, Davelene D.; Liu, Shun-Mei; Neal-Perry, Genevieve; Chua, Streamson C.

    2013-01-01

    Deficient leptin signaling causes infertility via reduced activity of GnRH neurons, causing a hypogonadal state in both rodents and humans. Because GnRH neurons do not express leptin receptors, leptin's effect on GnRH neurons must be indirect. Neurons within the hypothalamic arcuate nucleus that coexpress AGRP and NPY are considered to be important intermediate neurons involved in leptin regulation of GnRH neurons. Previously, we reported that the absence of AGRP and haploinsufficiency of MC4...

  1. Morphology of accessory genital glands of spotted paca (Agouti paca Linnaeus, 1766).

    Science.gov (United States)

    Borges, Edson Moreira; Branco, Érika; de Lima, Ana Rita; Leal, Leonardo Martins; Martins, Leandro Luiz; Reis, Ana Carolina Gonçalves; Cruz, Claudinei; Machado, Márcia Rita Fernandes; Miglino, Maria Angelica

    2014-02-01

    The spotted paca is the second largest rodent in Brazil, where it is of great economic interest in impoverished regions in view of its prominence as a low-cost source of protein. Little is known about the morphology of the accessory genital glands of this species. Thus, we studied the position and morphology of the genitals in ten adult male spotted pacas. The animals were divided into two groups, five animals were used for fixing of samples in 10% aqueous formaldehyde for macroscopic studies and the other five animals were designated for microscopic analysis. These were arranged in pairs and had the vesicular, prostate, coagulating and bulbourethral glands identified, being structured as mucous glands, which lead into the pelvic urethra. It was concluded that the accessory genital glands found in the paca are the same as those found in most rodents, showing similar histological aspects. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Agouti-related peptide plays a critical role in leptin's effects on female puberty and reproduction.

    Science.gov (United States)

    Sheffer-Babila, Sharone; Sun, Yan; Israel, Davelene D; Liu, Shun-Mei; Neal-Perry, Genevieve; Chua, Streamson C

    2013-12-01

    Deficient leptin signaling causes infertility via reduced activity of GnRH neurons, causing a hypogonadal state in both rodents and humans. Because GnRH neurons do not express leptin receptors, leptin's effect on GnRH neurons must be indirect. Neurons within the hypothalamic arcuate nucleus that coexpress AGRP and NPY are considered to be important intermediate neurons involved in leptin regulation of GnRH neurons. Previously, we reported that the absence of AGRP and haploinsufficiency of MC4R in leptin receptor mutant (Lepr(db/db)) females result in restoration of fertility and lactation despite the persistence of obesity and insulin resistance. The overarching hypothesis in the present study is that the absence or reduction of leptin's inhibition of AGRP/NPY neurons leads to suppression of GnRH release in cases of leptin signaling deficiency. Since TAC2 (NKB)-TAC3R signaling plays a role in puberty maturation and is modulated by metabolic status, the other aim of this study is to test whether TAC2/NKB neurons in ARC regulated by melanocortinergic signals herein affect leptin's action on puberty and reproduction. Our data showed that AGRP deficiency in Lepr(db/db) females restores normal timing of vaginal opening and estrous cycling, although uterine weight gain and mammary gland development are morphologically delayed. Nonetheless, Agrp(-/-) Lepr(db/db) females are fertile and sustain adequate nutrition of pups with lactation to weaning age. AGRP deficiency results in advanced vaginal opening in wild-type female mice. The postpubertal increase in hypothalamic TAC2 mRNA was not observed in Lepr(db/db) females, whereas AGRP deficiency restored it in Lepr(db/db) females. Additionally, MC4R activation with MTII induced FOS expression in TAC2 neurons, supporting the concept of melanocortinergic regulation of TAC2 neurons. These studies suggest that AGRP imposes an inhibitory effect on puberty and that TAC2 neurons may transmit melanocortinergic inhibition of GnRH neurons.

  3. Scatter hoarding by the Central American agouti : a test of optimal cache spacing theory

    NARCIS (Netherlands)

    Galvez, Dumas; Kranstauber, Bart; Kays, Roland W.; Jansen, Patrick A.

    2009-01-01

    Optimal cache spacing theory predicts that scatter-hoarding animals store food at a density that balances the gains of reducing cache robbery against the costs of spacing out caches further. We tested the key prediction that cache robbery and cache spacing increase with the economic value of food:

  4. Scatter hoarding by the Central American agouti: a test of optimal cache spacing theory

    NARCIS (Netherlands)

    Gálvez, D.; Kranstauber, B.; Kays, R.W.; Jansen, P.A.

    2009-01-01

    Optimal cache spacing theory predicts that scatter-hoarding animals store food at a density that balances the gains of reducing cache robbery against the costs of spacing out caches further. We tested the key prediction that cache robbery and cache spacing increase with the economic value of food:

  5. Utilização dos recursos naturais por comunidades humanas do Parque Ecoturístico do Guamá, Belém, Pará Utilization of natural resources by the human communities of the Guamá Ecotouristic Park, Belém, Pará

    Directory of Open Access Journals (Sweden)

    Ana Sílvia Sardinha Ribeiro

    2007-06-01

    Full Text Available O trabalho apresenta dados sobre o uso dos recursos naturais por populações humanas em pequenas comunidades (vilas localizadas no entorno (n = 6 e no interior (n = 1 do Parque Ecoturístico do Guamá (PEG, visando avaliar os impactos sobre a fauna e flora local, ante a implantação de um projeto de infra-estrutura rodoviária local. A metodologia consistiu da aplicação de dois modelos de questionários. Um direcionado a pessoas-chave, como: moradores mais antigos, presidentes de associações, agentes de saúde, etc, e o outro aplicado aleatoriamente aos adultos locais. Buscou-se atingir pelo menos 50% das famílias das pequenas localidades (11 famílias. Em todos os casos é realizado o extrativismo da fauna e flora, principalmente com o objetivo de subsistência. As espécies mais caçadas foram Agouti paca,Dasyprocta agouti,Nasua nasua, Euphractus sexcintus e Hydrochaeris hydrochaeris. A complementação da renda familiar através do comércio de caça sob encomenda é realizada em todas as comunidades estudadas. Frutíferas como Euterpe oleracea Mart., Musa spp e Theobroma cacao foram encontradas em 100% das comunidades (n=7. Plantas medicinais são rotineiramente cultivadas e empregadas. As espécies madeireiras exploradas são utilizadas com o objetivo de produção de carvão, construção de casas e de meios de transporte, predominando o Inga edulis, Virola surinamensis (Rol. Warb e Simaruba amara (Aubl.. O trabalho discute os resultados sob o aspecto da implantação do projeto viário, oferecendo recomendações para a minimização dos impactos do mesmo sobre a fauna, a flora e o modo tradicional de vida das comunidades.This work shows data about the use of natural resources by the human population located in (n=1 and around (n=6 the Guamá Ecotouristic Park (GEP, in order to evaluate the impact on the local fauna and flora in view of the project for constructing a road through the park. The methodology utilized in this community

  6. Scatter hoarding of seeds confers survival advantages and disadvantages to large-seeded tropical plants at different life stages.

    Science.gov (United States)

    Kuprewicz, Erin K

    2015-01-01

    Scatter hoarding of seeds by animals contributes significantly to forest-level processes, including plant recruitment and forest community composition. However, the potential positive and negative effects of caching on seed survival, germination success, and seedling survival have rarely been assessed through experimental studies. Here, I tested the hypothesis that seed burial mimicking caches made by scatter hoarding Central American agoutis (Dasyprocta punctate) enhances seed survival, germination, and growth by protecting seeds from seed predators and providing favorable microhabitats for germination. In a series of experiments, I used simulated agouti seed caches to assess how hoarding affects seed predation by ground-dwelling invertebrates and vertebrates for four plant species. I tracked germination and seedling growth of intact and beetle-infested seeds and, using exclosures, monitored the effects of mammals on seedling survival through time. All experiments were conducted over three years in a lowland wet forest in Costa Rica. The majority of hoarded palm seeds escaped predation by both invertebrates and vertebrates while exposed seeds suffered high levels of infestation and removal. Hoarding had no effect on infestation rates of D. panamensis, but burial negatively affected germination success by preventing endocarp dehiscence. Non-infested palm seeds had higher germination success and produced larger seedlings than infested seeds. Seedlings of A. alatum and I. deltoidea suffered high mortality by seed-eating mammals. Hoarding protected most seeds from predators and enhanced germination success (except for D. panamensis) and seedling growth, although mammals killed many seedlings of two plant species; all seedling deaths were due to seed removal from the plant base. Using experimental caches, this study shows that scatter hoarding is beneficial to most seeds and may positively affect plant propagation in tropical forests, although tradeoffs in seed

  7. Scatter hoarding of seeds confers survival advantages and disadvantages to large-seeded tropical plants at different life stages.

    Directory of Open Access Journals (Sweden)

    Erin K Kuprewicz

    Full Text Available Scatter hoarding of seeds by animals contributes significantly to forest-level processes, including plant recruitment and forest community composition. However, the potential positive and negative effects of caching on seed survival, germination success, and seedling survival have rarely been assessed through experimental studies. Here, I tested the hypothesis that seed burial mimicking caches made by scatter hoarding Central American agoutis (Dasyprocta punctate enhances seed survival, germination, and growth by protecting seeds from seed predators and providing favorable microhabitats for germination. In a series of experiments, I used simulated agouti seed caches to assess how hoarding affects seed predation by ground-dwelling invertebrates and vertebrates for four plant species. I tracked germination and seedling growth of intact and beetle-infested seeds and, using exclosures, monitored the effects of mammals on seedling survival through time. All experiments were conducted over three years in a lowland wet forest in Costa Rica. The majority of hoarded palm seeds escaped predation by both invertebrates and vertebrates while exposed seeds suffered high levels of infestation and removal. Hoarding had no effect on infestation rates of D. panamensis, but burial negatively affected germination success by preventing endocarp dehiscence. Non-infested palm seeds had higher germination success and produced larger seedlings than infested seeds. Seedlings of A. alatum and I. deltoidea suffered high mortality by seed-eating mammals. Hoarding protected most seeds from predators and enhanced germination success (except for D. panamensis and seedling growth, although mammals killed many seedlings of two plant species; all seedling deaths were due to seed removal from the plant base. Using experimental caches, this study shows that scatter hoarding is beneficial to most seeds and may positively affect plant propagation in tropical forests, although

  8. Scatter Hoarding of Seeds Confers Survival Advantages and Disadvantages to Large-Seeded Tropical Plants at Different Life Stages

    Science.gov (United States)

    Kuprewicz, Erin K.

    2015-01-01

    Scatter hoarding of seeds by animals contributes significantly to forest-level processes, including plant recruitment and forest community composition. However, the potential positive and negative effects of caching on seed survival, germination success, and seedling survival have rarely been assessed through experimental studies. Here, I tested the hypothesis that seed burial mimicking caches made by scatter hoarding Central American agoutis (Dasyprocta punctate) enhances seed survival, germination, and growth by protecting seeds from seed predators and providing favorable microhabitats for germination. In a series of experiments, I used simulated agouti seed caches to assess how hoarding affects seed predation by ground-dwelling invertebrates and vertebrates for four plant species. I tracked germination and seedling growth of intact and beetle-infested seeds and, using exclosures, monitored the effects of mammals on seedling survival through time. All experiments were conducted over three years in a lowland wet forest in Costa Rica. The majority of hoarded palm seeds escaped predation by both invertebrates and vertebrates while exposed seeds suffered high levels of infestation and removal. Hoarding had no effect on infestation rates of D. panamensis, but burial negatively affected germination success by preventing endocarp dehiscence. Non-infested palm seeds had higher germination success and produced larger seedlings than infested seeds. Seedlings of A. alatum and I. deltoidea suffered high mortality by seed-eating mammals. Hoarding protected most seeds from predators and enhanced germination success (except for D. panamensis) and seedling growth, although mammals killed many seedlings of two plant species; all seedling deaths were due to seed removal from the plant base. Using experimental caches, this study shows that scatter hoarding is beneficial to most seeds and may positively affect plant propagation in tropical forests, although tradeoffs in seed

  9. On the mammals collected by Friedrich Sellow in Brazil and Uruguay (1814-1831), with special reference to the types and their provenance.

    Science.gov (United States)

    Garbino, Guilherme S T; Nogueira, Marcelo R

    2017-01-17

    From 1814 to 1831, the Prussian naturalist Friedrich Sellow collected 263 mammals in Brazil and Uruguay. Upon receiving the specimens, the curator of the Berlin Zoological Museum, Martin Lichtenstein, removed the original labels and replaced with ones containing more generalized locations. As a consequence, several type specimens have now dubious type localities. We examined these types as well as geographically restricted mammals collected by Sellow. In some cases, there are inconsistencies between the specimen label and the collection catalog regarding the collecting locality. We conclude that the locality information on the lectotype of the tent-making bat Uroderma bilobatum is mistakenly identified, and therefore, we restrict it to "eastern Brazil". We designate a lectoype for Azara's agouti, Dasyprocta azarae, and restrict its type locality to the region travelled by Sellow in São Paulo. Although there are no recent records of the woolly giant rat, Kunsia tomentosus, from its type locality, the species may have been recently extirpated from the area. Two primate specimens supposedly collected by Sellow, a silvery marmoset, Mico argentatus, and a black tamarin, Saguinus niger, occur only in the Amazonia of northern Brazil, outside the route travelled by the naturalist, and are more likely to have been collected by Sieber. Our investigations stress the importance of collecting vouchers for verifying species occurrence records and establishing a solid taxonomy.

  10. Le mini-élevage, son développement villageoiset l'action de BEDIM

    Directory of Open Access Journals (Sweden)

    Jacques Hardouin

    1997-01-01

    Full Text Available Minilivestock, village development and the role of BEDIM.Minilivestock encompasses all animals of small site, and little-known in terras of production but usable as food, feed or revenues if not eaten. Sustainable breeding becomes possible, and should progressively replace uncontrolled gathering in the wild. Amongst vertebrates, an important meat supply is based on edible rodents like Thryonomys, Cricetomys, Xerus, Atherurus, Tenrec; Hydrochoerus, Dasyprocta, Myocastor, Capromys, Dolichotis, Agouti, etc. The saine applies to the guinea-pig Cavia porcellus and to frogs. Invertebrates farming is also practised through breeding of maggots, termites, butterflies (pupae and adults for consumption or sale; giant snails are also highly appreciated in many African countries. Minilivestock development is usually a back-yard activity, hence its interest as it relies on local species, substrates and raw materials for infrastructure. The demand for minilivestock product is high but there is still reluctance often from the official authorities, unfortunately. However minilivestock is not an utopia, and a country like Papua-New-Guinea, which bas officially adopted minilivestock production as a tool to help to develop remote villages, is an excellent example of success

  11. Novel piroplasmid and Hepatozoon organisms infecting the wildlife of two regions of the Brazilian Amazon.

    Science.gov (United States)

    Soares, Herbert S; Marcili, Arlei; Barbieri, Amália R M; Minervino, Antonio H H; Moreira, Thiago Rocha; Gennari, Solange M; Labruna, Marcelo B

    2017-08-01

    During 2009-2012, wild animals were sampled in two areas within the Amazon biome of Brazil, in the states of Mato Grosso and Pará. Animal tissues and blood were molecularly tested for the presence of Piroplasmida (genera Babesia, Theileria, Cytauxzoon) or Hepatozoon DNA. Overall, 181 wild animals comprising 36 different species (2 reptiles, 5 birds, and 29 mammals) were sampled. The following Piroplasmida agents were detected: Cytauxzoon felis in one ocelot (Leopardus pardalis), Theileria cervi in two red brocket deer (Mazama americana), Theileria spp. in three nine-banded-armadillos (Dasypus novemcinctus), one agouti (Dasyprocta sp.), and four lowland pacas (Cuniculus paca), Babesia spp. in one common opossum (Didelphis marsupialis) and one white-lipped peccary (Tayassu pecari). The following Hepatozoon agents were detected: Hepatozoon sp. (possibly Hepatozoon caimani) in three spectacled caimans (Caiman crocodilus), Hepatozoon felis in an ocelot (Leopardus pardalis), and Hepatozoon spp. in one scorpion mud turtle (Kinosternon scorpioides) and one lowland paca (Cuniculus paca). Phylogenetic analyses inferred by the 18S rRNA gene partial sequences supported these results, highlighting at least five novel Piroplasmida agents, and two novel Hepatozoon agents. This study screened the presence of tick-borne protozoa in a number of wildlife species from the Amazon for the first time. Our results indicate that a variety of genetically distinct Piroplasmida and Hepatozoon organisms circulate under natural conditions in the Amazonian wildlife.

  12. Novel piroplasmid and Hepatozoon organisms infecting the wildlife of two regions of the Brazilian Amazon

    Directory of Open Access Journals (Sweden)

    Herbert S. Soares

    2017-08-01

    Full Text Available During 2009–2012, wild animals were sampled in two areas within the Amazon biome of Brazil, in the states of Mato Grosso and Pará. Animal tissues and blood were molecularly tested for the presence of Piroplasmida (genera Babesia, Theileria, Cytauxzoon or Hepatozoon DNA. Overall, 181 wild animals comprising 36 different species (2 reptiles, 5 birds, and 29 mammals were sampled. The following Piroplasmida agents were detected: Cytauxzoon felis in one ocelot (Leopardus pardalis, Theileria cervi in two red brocket deer (Mazama americana, Theileria spp. in three nine-banded-armadillos (Dasypus novemcinctus, one agouti (Dasyprocta sp., and four lowland pacas (Cuniculus paca, Babesia spp. in one common opossum (Didelphis marsupialis and one white-lipped peccary (Tayassu pecari. The following Hepatozoon agents were detected: Hepatozoon sp. (possibly Hepatozoon caimani in three spectacled caimans (Caiman crocodilus, Hepatozoon felis in an ocelot (Leopardus pardalis, and Hepatozoon spp. in one scorpion mud turtle (Kinosternon scorpioides and one lowland paca (Cuniculus paca. Phylogenetic analyses inferred by the 18S rRNA gene partial sequences supported these results, highlighting at least five novel Piroplasmida agents, and two novel Hepatozoon agents. This study screened the presence of tick-borne protozoa in a number of wildlife species from the Amazon for the first time. Our results indicate that a variety of genetically distinct Piroplasmida and Hepatozoon organisms circulate under natural conditions in the Amazonian wildlife.

  13. Técnica de fatiamento do ovário para obtenção de oócitos em cutias (Dasyprocta prymnolopha)

    OpenAIRE

    Maíra S. Ferraz; Felipe de Jesus Moraes Júnior; Matheus Levi T. Feitosa; Hatawa M. de Almeida; Dayseanny de O. Bezerra; Gerson T. Pessoa; Daniel M. de N. Albuquerque; Maria Acelina Martins de Carvalho

    2016-01-01

    Resumo: As biotécnicas da reprodução são importantes ferramentas para conservação de espécies domésticas e silvestres, pois permitem a recuperação e uso futuro de material reprodutivo. O objetivo deste estudo foi avaliar parâmetros morfológicos de CCOs de cutias, obtidos pela técnica de fatiamento do ovário para utilização em protocolos de maturação e fecundação na produção in vitro de embriões. Foram utilizadas dezessete cutias fêmeas do NEPAS, CCA- UFPI, com idade e peso médios de 3,9 anos ...

  14. Técnica de fatiamento do ovário para obtenção de oócitos em cutias (Dasyprocta prymnolopha

    Directory of Open Access Journals (Sweden)

    Maíra S. Ferraz

    2016-03-01

    Full Text Available Resumo: As biotécnicas da reprodução são importantes ferramentas para conservação de espécies domésticas e silvestres, pois permitem a recuperação e uso futuro de material reprodutivo. O objetivo deste estudo foi avaliar parâmetros morfológicos de CCOs de cutias, obtidos pela técnica de fatiamento do ovário para utilização em protocolos de maturação e fecundação na produção in vitro de embriões. Foram utilizadas dezessete cutias fêmeas do NEPAS, CCA- UFPI, com idade e peso médios de 3,9 anos e 2,16Kg, respectivamente, que foram submetidas à ovariossalpingohisterectomia. Os ovários após dissecados e pesados em balança de precisão, foram fatiados individualmente. Procedeu-se a busca e seleção dos CCOs em estereomicroscópio, os quais foram identificados e quantificados por cada ovário, além de classificados quanto a sua morfologia segundo a quantidade de camadas de células do cumulus e ao citoplasma em quatro graus. Verificou-se que a técnica de fatiamento do ovário possibilitou a obtenção de CCOs de cutias, com recuperação de grande quantidade e de variados graus de qualidade. Não houve correlações entre a idade dos animais e o peso dos ovários; a idade e o número de CCOs obtidos; entre o peso das cutias e o peso dos ovários e o número de CCOs obtidos.

  15. Estudo morfológico e morfométrico do ovário de cutias (Dasyprocta aguti, Linnaeus, 1766

    Directory of Open Access Journals (Sweden)

    Mônica Marcos de Almeida

    2003-01-01

    Full Text Available Foram estudados 24 ovários pertencentes a 13 cutias adultas (em dois exemplares pesquisou-se apenas o ovário esquerdo, sendo 7 gestantes e 6 não gestantes, provenientes do Núcleo de Estudos e Preservação de Animais Silvestres da Universidade Federal do Piauí. Os órgãos foram observados in loco para descrição de sua topografia, mensurados, submetidos a cortes histológicos e observados em Microscópio Óptico. Os ovários apresentam-se de forma elipsóide, achatados dorsoventralmente, situando-se na região sub-lombar, caudalmente aos rins, com pequenas áreas transparentes em sua superfície externa. A margem mesovárica e a face lateral estão cobertas pelo mesossalpinge (bolsa ovárica. O ovário direito, apresenta em média: peso - 0,082g; comprimento - 0,83cm; largura - 0,49cm e espessura - 0,24cm; o ovário esquerdo: peso - 0,058g; comprimento - 0,74cm; largura - 0,45cm e espessura - 0,23cm. Histologicamente, constam de epitélio de revestimento cúbico simples, córtex periférico e medula central, constituída basicamente por tecido conjuntivo frouxo entremeado por vasos sangüíneos. Nas fêmeas gestantes foram observados de dois a três grandes corpos lúteos centrais e muitos outros menores periféricos; nas não gestantes os corpos lúteos são menores e mais numerosos. O córtex é rico em tipos celulares de natureza conjuntiva e em folículos em diferentes estágios de amadurecimento, os quais migram da margem mesovárica para a extremidade tubárica à medida que aumentam de tamanho. Conclui-se que os ovários da cutia, macro e microscopicamente, seguem o padrão observado nos demais roedores sexualmente ativos.

  16. An avifaunal survey of the Istranca mountains, turkish thrace: novel breeding bird records including the first breeding record of Wood Warbler Phylloscopus sibilatrix in Turkey

    DEFF Research Database (Denmark)

    Özkan, Korhan

    2011-01-01

    breeding evidence for Great Cormorant Phalacrocorax carbo, European Shag P. aristotelis, Pygmy Cormorant P. pygmeus, Garganey Anas querquedula, Common Redshank Tringa totanus, Alpine Swift Apus melba, Eurasian Wryneck Jynx torquilla, Red-rumped Swallow Cecropis daurica, White-throated Dipper Cinclus...

  17. Hemi-ovariossalpingohisterectomia em pacas prenhes e posterior ocorrência de prenhez (Agouti paca, Linnaeus, 1766 Hemiovarysalpingohysterectomy in pregnant pacas and further occurrency of pregnancy (Agouti paca, Linnaeus, 1766

    Directory of Open Access Journals (Sweden)

    Fabrício Singaretti de Oliveira

    2003-06-01

    Full Text Available Foi descrita a hemi-ovariossalpingohisterectomia em cinco pacas prenhes mantidas em cativeiro no Setor de Animais Silvestres da Faculdade de Ciências Agrárias e Veterinárias (FCAV-UNESP de Jaboticabal, São Paulo, Brasil, a fim de observar futura prenhez no corno restante. A tranqüilização foi obtida após aplicação de azaperone (4mg/kg seguida da aplicação de sulfato de atropina (0,06mg/kg e da associação de cloridrato de quetamina (20mg/kg e cloridrato de xilazina (1,5mg/kg, ambos na mesma seringa, para indução da anestesia. A anestesia geral foi obtida mediante inalação de halotano por máscara. Por meio de laparotomia mediana, foram retirados o corno uterino prenhe, o ovário e a tuba uterina, todos do mesmo antímero. Antibióticos (30.000UI/kg de três penicilinas e 12,5mg/kg de duas estreptomicinas e analgésico (0,02mg/kg de buprenorfina foram aplicados imediatamente após a cirurgia, sendo repetidos após dois dias. Todas as aplicações foram feitas por via intramuscular. Apesar da permanência de apenas um ovário após a cirurgia, nova prenhez ocorreu no corno restante nas cinco fêmeas submetidas à cirurgia, com o nascimento de filhotes (apenas um por parto após 215, 248, 276, 302 e 310 dias da hemi-ovariossalpingohisterectomia.The hemiovarysalpingohysterectomy in five captive pregnant pacas kept on the Wild Animal Section at the College of Agricultural and Veterinarian Sciences (FCAV-UNESP in Jaboticabal, São Paulo, Brazil, was conducted aiming at verifying the further occurrence of pregnancy on the remaining uterine horn. The tranquilization was achieved by using azaperone (4mg/kg and consequent application of atropine sulphate (0.06mg/kg and the association of ketamine (20mg/kg and xylazine (1.5mg/kg cloridrates, on the same syringe, for induction of anesthesia. The general anesthesia was performed via a face mask with halothane. By means of median laparotomy, the uterine horn with the fetus, the ovary and the uterine tube, all from the same antimere, were taken out. Antibiotics (30,000IU/kg of three penicillins and 12.5mg/kg of two streptomycins and analgesic (buprenorfine 0.02 mg/kg were injected immediately after surgery and repeated after two days. All injections were made intramuscularly. In spite of the permanence of only one ovary after surgery, new pregnancy occurred in the remaining uterine horn in the five females which went through surgery, and the birth (solely one by delivery happened 210, 248, 276, 302 and 310 days after the hemiovarysalpingohysterectomy.

  18. Assessment of mammal reproduction for hunting sustainability through community-based sampling of species in the wild.

    Science.gov (United States)

    Mayor, Pedro; El Bizri, Hani; Bodmer, Richard E; Bowler, Mark

    2017-08-01

    Wildlife subsistence hunting is a major source of protein for tropical rural populations and a prominent conservation issue. The intrinsic rate of natural increase. (r max ) of populations is a key reproductive parameter in the most used assessments of hunting sustainability. However, researchers face severe difficulties in obtaining reproductive data in the wild, so these assessments often rely on classic reproductive rates calculated mostly from studies of captive animals conducted 30 years ago. The result is a flaw in almost 50% of studies, which hampers management decision making. We conducted a 15-year study in the Amazon in which we used reproductive data from the genitalia of 950 hunted female mammals. Genitalia were collected by local hunters. We examined tissue from these samples to estimate birthrates for wild populations of the 10 most hunted mammals. We compared our estimates with classic measures and considered the utility of the use of r max in sustainability assessments. For woolly monkey (Lagothrix poeppigii) and tapir (Tapirus terrestris), wild birthrates were similar to those from captive populations, whereas birthrates for other ungulates and lowland-paca (Cuniculus paca) were significantly lower than previous estimates. Conversely, for capuchin monkeys (Sapajus macrocephalus), agoutis (Dasyprocta sp.), and coatis (Nasua nasua), our calculated reproductive rates greatly exceeded often-used values. Researchers could keep applying classic measures compatible with our estimates, but for other species previous estimates of r max may not be appropriate. We suggest that data from local studies be used to set hunting quotas. Our maximum rates of population growth in the wild correlated with body weight, which suggests that our method is consistent and reliable. Integration of this method into community-based wildlife management and the training of local hunters to record pregnancies in hunted animals could efficiently generate useful information of life

  19. Seguimiento y monitoreo participativo de la actividad de cacería en la región de Puerto Nariño, Amazonas, Colombia

    Directory of Open Access Journals (Sweden)

    Rodríguez Carlos

    2004-12-01

    Full Text Available Se describen los patrones generales de la actividad de cacería en el casco urbano de Puerto Nariño a partir del registro continuo de las jornadas de caza durante el período de aguas ascendentes (enero-julio, 2003, a través de un análisis comparativo entre el aprovechamiento de fauna en las zonas de várzea y tierra firme, con una perspectiva integrada que incluye principios históricos, culturales y biológicos. Se determinan los parámetros de captura, esfuerzo y captura por unidad de esfuerzo (CPUE y se describe la composición y distribución de la captura. La captura total fue de 238 individuos correspondientes a 44 especies. Las especies
    con mayores valores de captura fueron Alouatta seniculus, Ara manilata y Phalacrocorax olivaceus, en la zona de várzea y en tierra firme fueron Agouti paca, Dasypus novemcinctus y Dasyprocta fuliginosa. Tomando la jornada como unidad de esfuerzo, se definen los tipos de jornada identificados, se analiza el esfuerzo perdido con base en las jornadas no exitosas y se describe la tipología de los cazadores. Entre algunos de los aspectos socioculturales que enmarcan la actividad de cacería, se describe la visión actual de la cacería por parte de los indígenas Ticuna de Puerto Nariño y los aspectos tradicionales que aún forman parte de esta actividad. El proyecto se abordó a través de una metodología participativa en la cual los pobladores locales se involucraron activamente en el monitoreo, proceso que permitió a los cazadores organizarse y continuar autónomamente con la toma de registros durante el período de aguas bajas.

  20. Increased food intake in growth hormone-transgenic common carp (Cyprinus carpio L.) may be mediated by upregulating Agouti-related protein (AgRP).

    Science.gov (United States)

    Zhong, Chengrong; Song, Yanlong; Wang, Yaping; Zhang, Tanglin; Duan, Ming; Li, Yongming; Liao, Lanjie; Zhu, Zuoyan; Hu, Wei

    2013-10-01

    In fish, food intake and feeding behavior are crucial for survival, competition, growth and reproduction. Growth hormone (GH)-transgenic common carp exhibit an enhanced growth rate, increased food intake and higher feed conversion rate. However, the underlying molecular mechanisms of feeding regulation in GH-transgenic (TG) fish are not clear. In this study, we observed feeding behavior of TG and non-transgenic (NT) common carp, and analyzed the mRNA expression levels of NPY, AgRP I, orexin, POMC, CCK, and CART I in the hypothalamus and telencephalon after behavioral observation. We detected similar gene expression levels in the hypothalamus of TG and NT common carp, which had been cultured in the field at the same age. Furthermore, we tested the effects of GH on hypothalamus fragments in vitro to confirm our findings. We demonstrated that TG common carp displayed increased food intake and reduced food consumption time, which were associated with a marked increase in hypothalamic AgRP I mRNA expression. Our results suggest that elevated GH levels may influence food intake and feeding behavior by upregulating the hypothalamic orexigenic factor AgRP I in GH-transgenic common carp. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Características regionais sobre a ultra-estrutura das células principais do epitélio do ducto epididimal de Agouti paca

    Directory of Open Access Journals (Sweden)

    Antonio Marcos Orsi

    2009-12-01

    Full Text Available As células principais (P do epitélio de revestimento do epidídimo de paca foram relacionadas com processos citofisiológicos de endocitoses do tipo adsortiva e de fase fluida, respectivamente, aparentemente realizando também secreção apócrina. Essas funções foram propostas embasando-se em características de ultra-estrutura das células P, em cujos citoplasma observaram-se um expressivo número de vesículas, com diferentes formas, tamanhos e presença de conteúdo internalizado em algumas das vesículas revestidas por endomembranas, ocorrendo ainda caveolas e vesículas diminutas localizadas junto à borda apical de microvilos. Ademais, observaram-se vesículas grandes e revestidas e/ou com superfícies lisas; endossomos, e lisossomos de localização predominantemente apical. Uma via de secreção apócrina foi sugerida com base na ocorrência de expansões (protrusões, citoplasmáticas intraluminais nas células P.

  2. Central Administration of Ghrelin and Agouti-Related Protein (83–132) Increases Food Intake and Decreases Spontaneous Locomotor Activity in Rats

    National Research Council Canada - National Science Library

    Tang-Christensen, Mads; Vrang, Niels; Ortmann, Sylvia; Bidlingmaier, Martin; Horvath, Tamas L; Tschöp, Matthias

    2004-01-01

    .... ghrelin stimulates food intake and promotes adiposity after peripheral or central administration, likely by activating hypothalamic neurons expressing the orexigenic neuropeptides neuropeptide Y (NPY...

  3. Maternal obesity in the agouti viable yellow (Avy) mouse produces defective secretory activation that is associated with mammary inflammation and activation of adrenocorticosteroid-dependent gene expression

    Science.gov (United States)

    Maternal obesity is known to interfere with normal lactation in women, rodents, and dairy animals. Obesity is also correlated with profound changes in an array of endocrine factors and is causally linked with inflammation and insulin resistance. Recent work suggests that elevated aldosterone actin...

  4. Dispersal of seeds of Hymenaea courbaril (Fabaceae in a logged rain forest in the Peruvian Amazonian Dispersão de sementes de Hymenaea courbaril (Fabaceae em uma floresta tropical úmida com exploração madeireira na Amazônia peruana

    Directory of Open Access Journals (Sweden)

    David L. Gorchov

    2004-01-01

    Full Text Available Seed dispersal of Hymenaea courbaril was studied by following the fate of 585 seeds embedded with small magnets and set in displays in and near a logged strip in rain forest in the Peruvian Amazonian. Mammals took fruits from all displays, which were located in the forest, edge, and cleared strip. Overall removal rates were low - a median of 8.1 fruits / month from displays maintained with 8-10 fruits - but were higher in August than in earlier months. Most fruits were dropped near the display or had their seeds eaten, but > 13% were successfully dispersed. Most of the dispersed seeds were buried, which increases probability of germination. Maximum dispersal distance of live seeds was 12.1 m (median 3.1 m, but other magnets were transported up to 34 m, indicating seeds were dispersed further, but then eaten. Acouchies (most likely Myoprocta pratti and agoutis (Dasyprocta fuliginosa were apparently the main dispersal agents. Dispersal of seeds from the forest into the logged strip was rare, suggesting that although rodents disperse H. courbaril, they cannot be relied on for the reseeding this and similar species in recent clearings.Foi estudada a dispersão de sementes de Hymenaea courbaril, seguindo o destino de 585 sementes marcadas com imãs e expostas a potenciais dispersores, colocadas em agregados no interior e próximo de uma faixa de floresta cortada, na Amazónia peruana. Mamíferos retiraram frutos de todos os agregados, localizados no interior da floresta, na sua borda, e na clareira. As taxas de remoção foram baixas - mediana de 8.1 frutos/mês em agregados mantidos com 8-10 frutos - mas foram mais altas em agosto que nos primeiros meses do ano. A maior parte dos frutos foi abandonada próxima do agregado de origem ou as suas sementes foram consumidas, mas > 13% foram dispersos com sucesso. A maior parte das sementes dispersas foi enterrada, o que favorece a germinação. A distância máxima de dispersão de sementes vivas foi de

  5. Effects of the nonagouti coat-color allele on behavior of deer mice (Peromyscus maniculatus): a comparison with Norway rats (Rattus norvegicus).

    Science.gov (United States)

    Hayssen, V

    1997-12-01

    The agouti locus influences coat color by antagonizing melanocyte-stimulating hormone (MSH) at its receptor on pigment cells and may antagonize MSH in neural tissue. This study replicates work on rats to assess whether behavioral (neural) effects of the agouti locus are as similar across mammals as those on coat color. Handling, open-field, platform jump, and food-novelty tests were conducted on agouti and nonagouti deer mice (Peromyscus maniculatus) following protocols in C. A. Cottle and E. O. Price (1987). As with rats, nonagouti deer mice were less aggressive, less active, and easier to handle compared with their agouti counterparts. Nonagouti deer mice also groomed more than agouti subjects. Thus, behavioral effects of the agouti locus are conservative, and agouti may be an important modulator of melanocortins in neural as well as integumentary tissue.

  6. Breeding success of Cacicus haemorrhous (Linnaeus (Aves: Icteridae in different environments in an Atlantic Forest reserve in Southeast Brazil Sucesso reprodutivo de Cacicus haemorrhous (Linnaeus (Aves: Icteridae em diferentes ambientes de uma reserva de Mata Atlântica no sudeste do Brasil

    Directory of Open Access Journals (Sweden)

    Charles Duca

    2008-06-01

    Full Text Available Several factors, including the site where the colony was established and number of active nests can influence directly or indirectly the breeding success of colonial birds. The red-rumped cacique, Cacicus haemorrhous (Linnaeus, 1766, is a passerine (Icteridae that breeds in colonies in different environments. The objective of this study was to evaluate the breeding success of red-rumped cacique in relation to three environments (lake edge, forest and swamp in which colonies were established in an Atlantic Forest reserve in southeast Brazil. Seven colonies from the three environments were monitored during the breeding season of 2001. Overall probability of nest survival was 40.5%. We found that colonies established in the swamp presented higher nest survival than the others and the ones in the lake edge had lower survival. Nest predation was the most important cause of nest failure, representing 46.5% of all nest losses. Other failure causes were abandonment and fall of nests, representing 6.6% and 6.1% of the losses, respectively. Red-rumped cacique had higher success breeding in colonies located in the swamp.Diversos fatores, incluindo os locais onde as colônias são estabelecidas e o número de ninhos ativos, podem exercer uma influência direta ou indireta no sucesso reprodutivo de aves que reproduzem em colônias. O Guaxe é uma espécie de Passeriformes (Icteridae que se reproduz em colônias situadas em diferentes ambientes. O objetivo deste estudo foi avaliar o sucesso reprodutivo de Cacicus haemorrhous (Linnaeus, 1766 em relação a três ambientes (margem de lago, floresta e brejo onde são estabelecidas colônias em uma reserva de Mata Atlântica no sudeste do Brasil. Sete colônias foram monitoradas durante a estação reprodutiva de 2001 apresentando uma probabilidade de sobrevivência dos ninhos de 40,5%. As colônias estabelecidas em brejos apresentaram sucesso reprodutivo significativamente maior do que colônias estabelecidas

  7. Seed predation by mammals in forest fragments in Monteverde, Costa Rica

    Directory of Open Access Journals (Sweden)

    Federico A Chinchilla

    2009-09-01

    Full Text Available Few studies have evaluated seed predation in fragmented landscapes, in which lower species diversity is expected to modifying ecological interactions. The rates of seed removal by mammals were investigated in a continuous forest and two fragmented patches of Premontane Tropical Moist Forest, in Monteverde, Costa Rica. The composition of mammalian seed-predators in each site was recorded during 16 months. The removal of four native tree species of experimental seeds: Ocotea valeriana and Ocotea whitei (Lauraceae, Panopsis costaricensis (Proteaceae and Billia colombiana (Hippocastanaceae in forest understories was followed during two annual fruiting seasons for each species. Results indicated similar species composition of seed-predators between continuous forest, the largest fragment (350 ha. However the smaller fragment (20 ha, had fewer seed predators. In this fragment, the specialized seed predator Heteromys desmarestianus (Rodentia was more abundant. Unexpectedly, seed-predation in the two forest fragments and the continuous forest did not differ statistically for any of the seed species. Apparently, the higher abundance of small seed-predators in the fragments was compensated by the absence of medium and large seed-predators, like Agouti paca, Dasyprocta punctata (both Rodentia and Pecari tajacu (Artiodactyla recorded in continuous forest. Removal of experimentally-placed seeds was higher when the number of naturally occurring seeds in the sites was lower. This result could best be attributed to differential satiation of seed predators rather than differences in richness or abundance of seed predators. Rev. Biol. Trop. 57 (3: 865-877. Epub 2009 September 30.Pocos estudios han evaluado la depredación de semillas en ambientes fragmentados, en éstos la menor diversidad de especies debe estar modificando las interacciones ecológicas. Se investigó la remoción de semillas por mamíferos en un bosque continuo y dos fragmentos en Monteverde

  8. Epigenetic’s role in fish pigmentation

    Directory of Open Access Journals (Sweden)

    Laura Cal Delgado

    2014-04-01

    Full Text Available The agouti coat colour gene encodes a paracrine signalling molecule whose differential expression produces the characteristic dorsal-ventral pigment pattern observed in most mammals. We have recently demonstrated that this well-characterised mechanism from mammals also applies to fish with their much more complex pigment patterns. However, the developmental mechanism through which agouti acts to establish these colour differences remains unclear. The present study was undertaken to explore the molecular mechanisms that regulate agouti gene expression by in-vivo functional characterization of the agouti promoter and identification of possible putative regulatory elements that govern basal promoter activity. Specifically, the investigation was focused on the occurrence and role of CpG dinucleotides methylation in the agouti putative promoter sequence and on a possible epigenetic level of regulation of agouti expression. We report here expression analyses of eGFP expression from transgenic zebrafish containing an 8kb-agouti-Tol2-eGFP construct. eGFP expression was specifically found in the brain area and neural tube of Tol2 transposon vector transgenic embryos. Computer-based analysis revealed a putative CpG island immediately proximal to the translation start site. Global inhibition of methylation with 5-aza-2'-deoxycytidine promoted agouti production in association with decreasing CpG methylation. Taken together, these data identify a contributory role for DNA methylation in regulating agouti expression in zebrafish embryogenesis.

  9. Phenotypic features of Cameroon native goats under traditional ...

    African Journals Online (AJOL)

    According to coat color patterns polymorphisms, goat populations are highly variegated with agouti Primarity Index (aPI) and segregation at agouti locus Primarity Index (sPI) equal to 1. Coat colors varied from solid black to full white, with many black, red, brown, and white combinations, with black predominant. Mean body ...

  10. Efecto de las actividades humanas sobre la diversidad de mamíferos terrestres en un gradiente altitudinal

    Directory of Open Access Journals (Sweden)

    Lilliana Piedra C

    2000-03-01

    Full Text Available The effect of human activity on terrestrial mammals was studied with footprint counts in Guanacaste, Costa Rica (10°30'N, 85°40'W in February 1998 (in fifty 2 m² quadrats. The most common species were Canis latrans, Didelphis marsupialis, Odoicoleus virginianus, Dasyprocta punctata and Tapirus bairdii. No stastically significant association was found between humna activity and mammal frequency in the footprint counts.

  11. Dispersión de semillas de Mauritia flexuosa (Arecaceae) por frugívoros terrestres en Laguna Azul, Beni, Bolivia

    OpenAIRE

    MENDIETA-AGUILAR,Geovanna; Luis F. Pacheco; ROLDÁN,Alejandra I.

    2015-01-01

    El acopio esparcido ha recibido singular atención en las últimas décadas, y muchos estudios se han centrado en semillas de palmeras dispersadas por Dasyprocta. Nuestro objetivo fue identificar las especies consumidoras de frutos de Mauritia flexuosa, evaluar la importancia relativa de esas especies y el destino de las semillas dispersadas. Utilizamos experimentos de campo para evaluar el destino de las semillas removidas por frugívoros, en la Reserva de la Biosfera Pil...

  12. Relative abundance and activity patterns of terrestrial mammalian species, in Barra del Colorado Wildlife Refuge, Costa Rica

    OpenAIRE

    Stephanny Arroyo-Arce, Arroyo-Arce; Thomson, Ian; Salom-Pérez, Roberto

    2016-01-01

    Relatively little information has been generated regarding the mammal diversity of Barra del Colorado Wildlife Refuge, Costa Rica. This study assessed relative abundance and activity patterns of some terrestrial mammalian species. We used ten camera traps distributed within the refuge, during 2014. After a total of 1 611 camera trap nights, we identified 15 mammalian species in seven orders and 11 families. The most abundant species were Dasyprocta punctata, Leopardus pardalis, Tayassu pecari...

  13. Inhibition of hypothalamic Foxo1 expression reduced food intake in diet-induced obesity rats

    National Research Council Canada - National Science Library

    Eduardo R. Ropelle; José R. Pauli; Patrícia Prada; Dennys E. Cintra; Guilherme Z. Rocha; Juliana C. Moraes; Marisa J. S. Frederico; Gabrielle da Luz; Ricardo A. Pinho; José B. C. Carvalheira; Licio A. Velloso; Mario A. Saad; Cláudio T. De Souza

    2009-01-01

    .... Foxo1 stimulates the transcription of the orexigenic neuropeptide Y and Agouti-related protein through the phosphatidylinositol-3-kinase/Akt signalling pathway, but the role of hypothalamic Foxo1...

  14. Natural Genetic Variation Underlying Differences in Peromyscus Repetitive & Social/Aggressive Behaviors

    OpenAIRE

    Shorter, Kimberly R.; Owen, Amy; Anderson, Vanessa; Hall-South, April C.; Hayford, Samantha; Cakora, Patricia; Crossland, Janet P.; Georgi, Velina R. M.; Perkins, Amy; Kelly, Sandra J.; Felder, Michael R.; Vrana, Paul B.

    2014-01-01

    Peromyscus maniculatus (BW) and P. polionotus (PO) are interfertile North American species that differ in many characteristics. For example, PO exhibit monogamy and BW animals are susceptible to repetitive behaviors and thus a model for neurobehavioral disorders such as Autism. We analyzed these two stocks as well as their hybrids, a BW YPO consomic line (previously shown to alter glucose homeostasis) and a natural P. maniculatus agouti variant (ANb = wide band agouti). We show that PO animal...

  15. Pleiotropic effects of a methyl donor diet in a novel animal model.

    Science.gov (United States)

    Shorter, Kimberly R; Anderson, Vanessa; Cakora, Patricia; Owen, Amy; Lo, Keswick; Crossland, Janet; South, April C H; Felder, Michael R; Vrana, Paul B

    2014-01-01

    Folate and other methyl-donor pathway components are widely supplemented due to their ability to prevent prenatal neural tube defects. Several lines of evidence suggest that these supplements act through epigenetic mechanisms (e.g. altering DNA methylation). Primary among these are the experiments on the mouse viable yellow allele of the agouti locus (A(vy)). In the Avy allele, an Intracisternal A-particle retroelement has inserted into the genome adjacent to the agouti gene and is preferentially methylated. To further test these effects, we tested the same diet used in the Avy studies on wild-derived Peromyscus maniculatus, a native North American rodent. We collected tissues from neonatal offspring whose parents were fed the high-methyl donor diet as well as controls. In addition, we assayed coat-color of a natural variant (wide-band agouti = A(Nb)) that overexpresses agouti as a phenotypic biomarker. Our data indicate that these dietary components affected agouti protein production, despite the lack of a retroelement at this locus. Surprisingly, the methyl-donor diet was associated with defects (e.g. ovarian cysts, cataracts) and increased mortality. We also assessed the effects of the diet on behavior: We scored animals in open field and social interaction tests. We observed significant increases in female repetitive behaviors. Thus these data add to a growing number of studies that suggest that these ubiquitously added nutrients may be a human health concern.

  16. Pleiotropic effects of a methyl donor diet in a novel animal model.

    Directory of Open Access Journals (Sweden)

    Kimberly R Shorter

    Full Text Available Folate and other methyl-donor pathway components are widely supplemented due to their ability to prevent prenatal neural tube defects. Several lines of evidence suggest that these supplements act through epigenetic mechanisms (e.g. altering DNA methylation. Primary among these are the experiments on the mouse viable yellow allele of the agouti locus (A(vy. In the Avy allele, an Intracisternal A-particle retroelement has inserted into the genome adjacent to the agouti gene and is preferentially methylated. To further test these effects, we tested the same diet used in the Avy studies on wild-derived Peromyscus maniculatus, a native North American rodent. We collected tissues from neonatal offspring whose parents were fed the high-methyl donor diet as well as controls. In addition, we assayed coat-color of a natural variant (wide-band agouti = A(Nb that overexpresses agouti as a phenotypic biomarker. Our data indicate that these dietary components affected agouti protein production, despite the lack of a retroelement at this locus. Surprisingly, the methyl-donor diet was associated with defects (e.g. ovarian cysts, cataracts and increased mortality. We also assessed the effects of the diet on behavior: We scored animals in open field and social interaction tests. We observed significant increases in female repetitive behaviors. Thus these data add to a growing number of studies that suggest that these ubiquitously added nutrients may be a human health concern.

  17. Impaired spatial performance in rats with retrosplenial lesions: importance of the spatial problem and the rat strain in identifying lesion effects in a swimming pool.

    Science.gov (United States)

    Harker, K Troy; Whishaw, Ian Q

    2002-02-01

    Behavioral, electrophysiological, and anatomical evidence suggests that retrosplenial (RS) cortex (areas RSA and RSG) plays a role in spatial navigation. This conclusion has been questioned in recent work, suggesting that it is damage to the underlying cingulum bundle (CG) (areas CG and IG), and not RS, that disrupts spatial place learning (Aggleton et al., 2000). We revisited this issue by comparing Long-Evans rats, the strain used in studies that report RS deficits, to Dark Agouti rats, the strain in which no RS deficit has been reported. Rat groups with RS, RS + CG, or no lesion were tested on a place task in a swimming pool, a test of nonspatial and spatial learning, and a matching-to-place task, a relatively selective test of spatial learning. Long-Evans rats given RS and RS + CG lesions, either before or after training on the two tasks, were impaired on both tasks, a deficit not attributable to impaired visual acuity. Control Dark Agouti rats and RS Dark Agouti rats, although not different on the place task, were both significantly impaired relative to Long-Evans rats. The RS Dark Agouti group, however, was also impaired on the matching-to-place task. Thus, we show that RS cortex is part of an extended neural circuit involved in spatial behavior in both Long-Evans and Dark Agouti rats, but its role in the place task may be masked by an innate nonspatial deficit in Dark Agouti rats. The results are discussed in relation to the importance of assessing spatial learning with appropriate spatial tests, the problems of interpretation posed by rat strain differences, and the role of retrosplenial cortex in spatial behavior.

  18. New mammalian records in the Parque Nacional Cerros de Amotape, northwestern Peru

    Directory of Open Access Journals (Sweden)

    Cindy M. Hurtado

    2015-04-01

    Full Text Available The Pacific Tropical Rainforest and Equatorial Dry Forest are found only in southern Ecuador and northern Peru, and are among the most poorly known ecosystems of South America. Even though these forests are protected in Parque Nacional Cerros de Amotape (PNCA, they are threatened by fragmentation because of farming and agriculture. The aim of this study was to determine the medium and large mammalian species richness, using transect census, camera trapping, and specimen bone collection. Nine transects were established and 21 camera trap stations were placed along 16 km2 in three localities of PNCA, from August 2012 to April 2013. Total sampling effort was 215 km of transects and 4077 camera-days. We documented 22 species; including 17 with camera trapping, 11 with transect census, and 10 with specimen collection.  Camera traps were the most effective method, and four species (Dasyprocta punctata, Cuniculus paca, Leopardus wiedii and Puma concolor were documented only with this method. This comprised the first Peruvian record for Dasyprocta punctata, and the first record for the western slope of the Peruvian Andes for Cuniculus paca. Also, both specimen collections and sightings confirm the presence of Potos flavus, first record in the western slope of the Peruvian Andes. Panthera onca, Tremarctos ornatus and Saimiri sciureus are considered locally extinct, while several species are in need of further research. We highlight the importance of the high diversity of this rainforests and encourage local authorities to give the area the highest priority in conservation.

  19. Presença de anticorpos da classe IgM de Leptospira interrogans em animais silvestres do Estado do Tocantins, 2002 Presence of IgM antibodies for Leptospira interrogans in wild animals from Tocantins State, 2002

    Directory of Open Access Journals (Sweden)

    Milton Formiga de Souza Júnior

    2006-06-01

    Full Text Available Quatrocentos e vinte e sete amostras de soro provenientes de animais silvestres foram testadas frente a 18 sorovariedades de Leptospira interrogans. De 286 amostras de Cebus apella, 46 (16,1% foram positivas para as sorovariedades pomona, brasiliensis, mini, swajizak, grippothyphosa, sarmin, fluminense, autumnalis, hebdomadis, guaratuba, javanica e icterohaemorhagiae. Das 82 de Alouatta caraya, 2 (2,4% foram positivas para as sorovariedades mangus e fluminense. Das 31 de Nasua nasua, 4 (12,9% foram positivas para as sorovariedades fluminense e javanica. Das 10 amostras de Cerdocyon thous, 2 (20% foram positivas para as sorovariedades fluminense e brasiliensis. Sete de Dasyprocta sp, 6 de Tamandua tetradactila e 5 de Euphractus sexcintus não apresentaram reatividade.Four hundred and twenty-seven serum samples of wild animals were tested against 18 serovars of Leptospira interrogans. Of 286 samples of Cebus apella, 46 (16.1% were positive for the serovars pomona, brasiliensis, mini, swajizak, grippotyphosa, sarmin, fluminense, autumnalis, hebdomadis, guaratuba, javanica and icterohaemorrhagiae. Of 82 samples of Alouatta caraya, 2 (2.4% were positive for the serovars mangus and fluminense. Of 31 samples of Nasua nasua, 4 (12.9% were positive for the serovars fluminense and javanica, and of 10 samples of Cerdocyon thous, 2 (20 % were positive for the serovars fluminense and brasiliensis. Seven samples of Dasyprocta sp, 6 of Tamandua tetradactyla and 5 of Euphractus sexcintus did not present reactivity.

  20. Differential expression of proteoglycans in tissue remodeling and lymphangiogenesis after experimental renal transplantation in rats.

    Science.gov (United States)

    Rienstra, Heleen; Katta, Kirankumar; Celie, Johanna W A M; van Goor, Harry; Navis, Gerjan; van den Born, Jacob; Hillebrands, Jan-Luuk

    2010-02-05

    Chronic transplant dysfunction explains the majority of late renal allograft loss and is accompanied by extensive tissue remodeling leading to transplant vasculopathy, glomerulosclerosis and interstitial fibrosis. Matrix proteoglycans mediate cell-cell and cell-matrix interactions and play key roles in tissue remodeling. The aim of this study was to characterize differential heparan sulfate proteoglycan and chondroitin sulfate proteoglycan expression in transplant vasculopathy, glomerulosclerosis and interstitial fibrosis in renal allografts with chronic transplant dysfunction. Renal allografts were transplanted in the Dark Agouti-to-Wistar Furth rat strain combination. Dark Agouti-to-Dark Agouti isografts and non-transplanted Dark Agouti kidneys served as controls. Allograft and isograft recipients were sacrificed 66 and 81 days (mean) after transplantation, respectively. Heparan sulfate proteoglycan (collXVIII, perlecan and agrin) and chondroitin sulfate proteoglycan (versican) expression, as well as CD31 and LYVE-1 (vascular and lymphatic endothelium, respectively) expression were (semi-) quantitatively analyzed using immunofluorescence. Arteries with transplant vasculopathy and sclerotic glomeruli in allografts displayed pronounced neo-expression of collXVIII and perlecan. In contrast, in interstitial fibrosis expression of the chondroitin sulfate proteoglycan versican dominated. In the cortical tubular basement membranes in both iso- and allografts, induction of collXVIII was detected. Allografts presented extensive lymphangiogenesis (pproteoglycans being expressed are tightly associated with tissue remodeling after renal transplantation. Therefore, proteoglycans might be potential targets for clinical intervention in renal chronic transplant dysfunction.

  1. Primarity and biometric indices of native goats in western Cameroon ...

    African Journals Online (AJOL)

    A total of 221 mature goats, both males and females were sampled in this investigation. Our findings showed that the native goats are dwarf or brevipes. Color patterns identified are very wide from monochrome to variegated spotting. Based on segregation and locus agouti distribution indices, the mean value of 0.9 and 1 ...

  2. Geometry and evolutionary parallelism in the long bones of cavioid ...

    Indian Academy of Sciences (India)

    other small forest-dwelling herbivorous mammals, such as the South American agouti (Dasyproctidae, Rodentia) and. African duikers (Cephalophinae) in having ... rodents and some small artiodactyls based on the biome- chanical aspects of limb structures. Because of scaling issues due to varying sizes of the compared ...

  3. Antimicrobial activity of Crataeva religiosa Forst against bacteria ...

    African Journals Online (AJOL)

    Jane

    2011-08-31

    Aug 31, 2011 ... An attempt has been made to carry out a screening on the antibacterial activity of leaves of Crateva religiosa Forst used in Benin traditional veterinary medicine against bacterial infection of Thryonomys swinderianus (class of Mammalia, family of Thryonomyidae) commonly called agouti or kholan. The aim.

  4. Thieving rodents as substitute dispersers of megafaunal seeds

    Science.gov (United States)

    Jansen, Patrick A.; Hirsch, Ben T.; Emsens, Willem-Jan; Zamora-Gutierrez, Veronica; Wikelski, Martin; Kays, Roland

    2012-01-01

    The Neotropics have many plant species that seem to be adapted for seed dispersal by megafauna that went extinct in the late Pleistocene. Given the crucial importance of seed dispersal for plant persistence, it remains a mystery how these plants have survived more than 10,000 y without their mutualist dispersers. Here we present support for the hypothesis that secondary seed dispersal by scatter-hoarding rodents has facilitated the persistence of these large-seeded species. We used miniature radio transmitters to track the dispersal of reputedly megafaunal seeds by Central American agoutis, which scatter-hoard seeds in shallow caches in the soil throughout the forest. We found that seeds were initially cached at mostly short distances and then quickly dug up again. However, rather than eating the recovered seeds, agoutis continued to move and recache the seeds, up to 36 times. Agoutis dispersed an estimated 35% of seeds for >100 m. An estimated 14% of the cached seeds survived to the next year, when a new fruit crop became available to the rodents. Serial video-monitoring of cached seeds revealed that the stepwise dispersal was caused by agoutis repeatedly stealing and recaching each other’s buried seeds. Although previous studies suggest that rodents are poor dispersers, we demonstrate that communities of rodents can in fact provide highly effective long-distance seed dispersal. Our findings suggest that thieving scatter-hoarding rodents could substitute for extinct megafaunal seed dispersers of tropical large-seeded trees. PMID:22802644

  5. Adaptive variation in beach mice produced by two interacting pigmentation genes.

    Directory of Open Access Journals (Sweden)

    Cynthia C Steiner

    2007-09-01

    Full Text Available Little is known about the genetic basis of ecologically important morphological variation such as the diverse color patterns of mammals. Here we identify genetic changes contributing to an adaptive difference in color pattern between two subspecies of oldfield mice (Peromyscus polionotus. One mainland subspecies has a cryptic dark brown dorsal coat, while a younger beach-dwelling subspecies has a lighter coat produced by natural selection for camouflage on pale coastal sand dunes. Using genome-wide linkage mapping, we identified three chromosomal regions (two of major and one of minor effect associated with differences in pigmentation traits. Two candidate genes, the melanocortin-1 receptor (Mc1r and its antagonist, the Agouti signaling protein (Agouti, map to independent regions that together are responsible for most of the difference in pigmentation between subspecies. A derived mutation in the coding region of Mc1r, rather than change in its expression level, contributes to light pigmentation. Conversely, beach mice have a derived increase in Agouti mRNA expression but no changes in protein sequence. These two genes also interact epistatically: the phenotypic effects of Mc1r are visible only in genetic backgrounds containing the derived Agouti allele. These results demonstrate that cryptic coloration can be based largely on a few interacting genes of major effect.

  6. Life or death? A Physiogenomic Approach to Understand Individual Variation in Responses to Hemorrhagic Shock

    Science.gov (United States)

    2011-01-01

    Sci. U S A, 2005, 102, 10604-10609. [142] Morgan, H. D.; Sutherland , H. G.; Martin, D. I.; Whitelaw, E. Epigenetic inheritance at the agouti locus...interplay between histone modifications and DNA methylation in gene silencing. Mutat. Res., 2008, 659, 40-48. [155] Cooney, C. A.; Dave , A. A

  7. Neuroprotection without immunomodulation is not sufficient to reduce first relapse severity in experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Hasseldam, Henrik; Johansen, Flemming Fryd

    2010-01-01

    relapse and related this to demyelination, axonal degeneration and relapse severity. METHODS: Experimental autoimmune encephalomyelitis was induced in Dark Agouti rats and treatment with R(+)WIN55,212-2 was initiated at symptom debut. The animals were scored clinically throughout the experiment...

  8. The chronology of age-related spatial learning impairment in two rat strains, as tested by the Barnes maze.

    Science.gov (United States)

    Barrett, Graham L; Bennie, Antoinette; Trieu, Jennifer; Ping, Sophie; Tsafoulis, Christine

    2009-06-01

    The Barnes maze offers advantages for cognitive aging studies, because of its relatively unstressful design and its modest physical demands. The authors therefore undertook a detailed chronological investigation of performance against age, for female Sprague-Dawley and male and female Dark Agouti rats. The trial duration was 10 days. Rats were tested at 6, 11, 14, 17, 20, and 26 months of age, but individual rats were tested at one age only. At 6 months of age, all rats reached the criterion. Sprague-Dawley rats performed best at this age. Impairment began at 14 months in Dark Agouti rats and continued to increase up to 26 months of age. Impairment was greater in Dark Agouti than Sprague-Dawley rats and was greater in females than males. At 26 months, 70% of Sprague-Dawley females reached criterion; of the Dark Agoutis, only 33% of females and 57% of males reached criterion. This study confirms the utility of the Barnes maze as a robust vehicle in aged rats. It also highlights major performance differences between strains and genders in aging rats. Copyright (c) 2009 APA, all rights reserved.

  9. Nutritional and endocrine modulation of intracellular calcium: implications in obesity, insulin resistance and hypertension.

    Science.gov (United States)

    Zemel, M B

    1998-11-01

    Regulation of intracellular Ca2+ ([Ca2+]i) plays a key role in obesity, insulin resistance and hypertension, and [Ca2+]i disorders may represent a fundamental factor linking these three conditions. We have shown insulin to be a direct vasodilator, attenuating voltage-gated Ca2+ influx and stimulating Ca(2+)-ATPase transcription via a glucose-6-phosphate response element. These result in a net decrease in [Ca2+]i and thereby decrease vascular resistance, while these effects are blunted in insulin resistance, leading to increased vascular resistance. Consistent with this concept, pharmacological amplification of peripheral insulin sensitivity results in reduced arterial pressure. While insulin regulates [Ca2+]i, Ca2+ also regulates insulin signaling, as increasing [Ca2+]i impairs insulin signaling in some systems, possibly due to Ca2+ inhibition of insulin-regulated dephosphorylation. Finally, in recent studies of the mouse agouti gene, we have also demonstrated increased [Ca2+]i to play a key role in adipocyte lipogenesis, as follows. We have found dominant agouti mutants to exhibit increased [Ca2+]i in most tissues, leading to increased vascular reactivity and insulin resistance in vascular smooth muscle and skeletal muscle cells, respectively. Further, we have found recombinant agouti protein to directly increase [Ca2+]i in a variety of cells, including murine and human adipocytes, and to stimulate both the expression and activity of adipocyte fatty acid synthase and increase triglyceride accumulation in a Ca(2+)-dependent manner. These effects can be mimicked by stimulation of Ca2+ influx and blocked by Ca2+ channel inhibition, while treatment of mice with a Ca2+ antagonist attenuates agouti-induced obesity. Since humans express agouti in adipose tissue, it may similarly exert paracrine effects on [Ca2+]i and thereby stimulate de novo lipogenesis and promote obesity. Thus, Ca2+ signaling represents a target for therapeutic intervention in obesity as well as

  10. Infecções experimentaes na Leishmaniose visceral americana Experimental infections in american visceral leishmaniasis

    Directory of Open Access Journals (Sweden)

    Aristides Marques da Cunha

    1938-01-01

    Leishmaniae being located mainly in the mucous membrane, in infiltration cells located amongst Lieberkuehn's glands and some parasited macrophages could also be observed in the sub-mucosa. Mice as well as the rodents Dasyprocta agouti and Proechymis oris when inoculated, did not become infeced. From the exposed we may conclude that the experimental infections obtained, present a complete analogy with those described in the Mediterrean Kala-azar. On the other hand, the sero-agglutination test, as shown by us in a previous paper, allows no distinction of the species of Leishmania, as all the strains when recently isolated, have the same antigenic constitution which later on undergoes modifications when the Leishmaniae are preserved in culture for a long time. Thus, we feel authorized to conclude that the agent of the visceral american leishmaniasis is identical with L. infantum.

  11. Notas sôbre a evolução do virus vacínico em animais silvestres da fauna brasileira

    Directory of Open Access Journals (Sweden)

    Cicero Alves Moreira

    1956-06-01

    Full Text Available A note on the evolution of cow-pox virus in wild animals of Brazilian fauna. We have tried the sensibility of wild animals of Brazilian fauna to the cow-pox virus. The following specimens were submitted to experiences: Procyon cancrivorus, Hydrochoerus capybara, Cavea aperea, Coendu villosus, Didelphis aurita, Bradypus tridactylus, Euphractus sexcintus, Tamandua tetradactylus, Nasua narica, Dasyprocta aguti and Testudo tabulata. In all these animals, - excepting Bradypus tridactylus - we have obtained an infection with incubation (five days, aspect and duration similar to cow-pox of the laboratorial animals (calf and rabbit. In the Bradypus tridactylus howewer, the incubation was very long. Only after 30 days of inoculation we verified the infection with the formation of vesiculae and postulae.

  12. Prevalence of Trypanosoma cruzi and Other Trypanosomatids in Frequently-Hunted Wild Mammals from the Peruvian Amazon.

    Science.gov (United States)

    Morales, E Angelo; Mayor, Pedro; Bowler, Mark; Aysanoa, Esar; Pérez-Velez, Erika S; Pérez, Jocelyn; Ventocilla, Julio A; Baldeviano, G Christian; Lescano, Andrés G

    2017-11-01

    To better understand the ecology of Trypanosoma cruzi in the northeastern Peruvian Amazon, we evaluated the prevalence of T. cruzi and other trypanosomatids in four orders of wild mammals hunted and consumed by inhabitants of three remote indigenous communities in the Peruvian Amazon. Of 300 wild mammals sampled, 115 (38.3%) were infected with trypanosomatids and 15 (5.0%) with T. cruzi. The prevalence of T. cruzi within each species was as follows: large rodents (Cuniculus paca, 5.5%; Dasyprocta spp., 2.6%), edentates (Dasypus novemcinctus, 4.2%), and carnivores with higher prevalence (Nasua nasua, 18.8%). The high prevalence of T. cruzi and other trypanosomatids in frequently hunted wild mammals suggests a sizeable T. cruzi sylvatic reservoir in remote Amazonian locations.

  13. The erythrocyte cytoskeleton protein 4.2 is not demonstrable in several mammalian species

    Directory of Open Access Journals (Sweden)

    E.M. Guerra-Shinohara

    1999-06-01

    Full Text Available Erythrocyte membrane proteins from 44 representative mammals were studied. Protein 4.2 was not detected in guinea pigs (Cavia porcellus (N = 14, Southern Brazilian swamp large rats (Myocastor coypus (N = 2, cutias (Dasyprocta sp (N = 4, and horses (Equus caballus (N = 13. These animals also presented high ankyrin concentrations except for the horse which did not exhibit a sharp band, although minor components located between proteins 2 and 3 could account for the ankyrin family. The rodents studied did present band 6, which was not detectable in other common rodents such as white rats (Rattus norvegicus (N = 9 and mice (Mus musculus (N = 12. Since the absence of protein 4.2 does not disrupt the cytoskeleton membrane, we suggest that it is not an essential protein. Its absence may be compensated physiologically by the higher ankyrin concentration observed.

  14. Temporal variation in the reproductive success of Cacicus haemorrhous (Linnaeus (Aves, Icterinae in an Atlantic Forest reserve in Southeast Brazil Variação temporal no sucesso reprodutivo de Cacicus haemorrhous (Linnaeus (Aves, Icterinae em uma reserva de Floresta Atlântica no sudeste do Brasil

    Directory of Open Access Journals (Sweden)

    Charles Duca

    2005-06-01

    Full Text Available For colonial bird species, egg hatching synchrony has been considered an important factor in their reproductive success. The Red-rumped Cacique, Cacicus haemorrhous (Linnaeus, 1766, is a Passeriformes species (Icterinae that reproduces in colonies in which groups of females lay their eggs at different periods during the reproductive season. The objective of this study was to evaluate if there was a variation in the reproductive success among C. haemorrhous females groups that lay eggs in different periods along the reproductive season. A total of 192 nests from four colonies were monitored at Parque Estadual do Rio Doce, Minas Gerais state, Brazil, and used to calculate the nest survival probability in different periods (early and late of the 2001 reproductive season. The results showed that females that reproduced at the beginning of the reproductive period had higher reproductive success than those that reproduced later. Predation was the main cause of nests loss (48,4%, and an increase in predation rate was observed as the reproductive period advanced.Para espécies de aves coloniais a sincronia de eclosão dos ovos tem sido considerada um fator que influencia o sucesso reprodutivo. O Guaxe, Cacicus haemorrhous (Linnaeus, 1766, é uma espécie de Passeriformes (Icterinae que se reproduz em colônias com grupos de fêmeas fazendo a postura em diferentes períodos ao longo da estação reprodutiva. O objetivo deste estudo foi avaliar se há uma variação no sucesso reprodutivo de C. haemorrhous entre esses grupos de fêmeas que fazem a postura em diferentes períodos ao longo da estação reprodutiva. Quatro colônias totalizando 192 ninhos foram monitoradas no Parque Estadual do Rio Doce, Minas Gerais, Brasil, calculando-se a probabilidade de sobrevivência dos ninhos em relação a diferentes períodos (cedo e tardio ao longo da estação reprodutiva de 2001. Constatou-se que fêmeas que reproduziram mais cedo na estação reprodutiva

  15. Genetic polymorphism of adult reindeer coat colour in a herding cooperative in Finnish Lapland

    Directory of Open Access Journals (Sweden)

    Jean J. Lauvergne

    2011-04-01

    Full Text Available In a random sample of 188 adult reindeer belonging to a reindeer herding cooperative in Finnish Lapland, the following coat colour mutants were identified: Abf at the locus Agouti (A, kalppinokka (WNk at the locus White Nose (WN and white at the locus W (White. Coefficients of coat colour phenotypic polymorphism K were estimated, in order to quantify this genetic polymorphism. Estimations of K were 12.8% for the locus A (Agouti, 5.1% for the locus WN (White Nose, and 7.5% for the locus W (White. This polymorphism results probably from a change in fitness coefficient of genotypes carrying colour mutants following domestication in a random mating context which has not yet been proved.

  16. Common commercial cosmetic products induce arthritis in the DA rat.

    OpenAIRE

    Sverdrup, B; Klareskog, L; Kleinau, S

    1998-01-01

    Many different agents, including mineral oil and silicone, have the capacity to act as immunological adjuvants, i.e., they can contribute to the activation of the immune system. Some adjuvants, including mineral oil, are known to induce arthritis in certain strains of rats after intradermal injection or percutaneous application. The aim of this study was to determine if common commercial cosmetic products containing mineral oil could induce arthritis in the highly susceptible DA (Dark Agouti)...

  17. G protein-coupled purinergic receptor GPR17 mediates orexigenic effects of FoxO1 in AgRP neurons

    OpenAIRE

    Ren, Hongxia; Orozco, Ian J.; Su, Ya; Suyama, Shigetomo; Gutiérrez-Juárez, Roger; Horvath, Tamas L.; Wardlaw, Sharon L.; Plum, Leona; Arancio, Ottavio; Accili, Domenico

    2012-01-01

    Hypothalamic neurons expressing Agouti-related peptide (AgRP) are critical for initiating food intake. But druggable biochemical pathways that control this response remain elusive. Thus, genetic ablation of anorexigenic signaling by insulin or leptin in AgRP neurons fails to affect food intake. FoxO1 is a shared mediator of both pathways, and its inhibition is required for their anorexigenic effects. We postulated that FoxO1 effectors include pathways regulating food intake. Accordingly, FoxO...

  18. Inhibition of hypothalamic Foxo1 expression reduced food intake in diet-induced obesity rats

    OpenAIRE

    Eduardo R. Ropelle; Pauli, Jose R.; Prada, Patricia; Cintra, Dennys E.; Rocha, Guilherme Z; Juliana C Moraes; Frederico, Marisa J.S.; Luz,Gabrielle da; Pinho, Ricardo A.; Carvalheira, Jose B. C.; Velloso, Licio A.; Saad, Mario A.; Souza, Claudio T. de

    2009-01-01

    Insulin signalling in the hypothalamus plays a role in maintaining body weight. the forkhead transcription factor Foxo1 is an important mediator of insulin signalling in the hypothalamus. Foxo1 stimulates the transcription of the orexigenic neuropeptide Y and Agouti-related protein through the phosphatidylinositol-3-kinase/Akt signalling pathway, but the role of hypothalamic Foxo1 in insulin resistance and obesity remains unclear. Here, we identify that a high-fat diet impaired insulin-induce...

  19. Astrocytes Modulate Distribution and Neuronal Signaling of Leptin in the Hypothalamus of Obese Avy Mice

    OpenAIRE

    Pan, Weihong; Hsuchou, Hung; Xu, Changlei; Wu, Xiaojun; Bouret, Sebastien G.; Kastin, Abba J

    2010-01-01

    We tested the hypothesis that astrocytic activity modulates neuronal uptake and signaling of leptin in the adult-onset obese agouti viable yellow (Avy) mouse. In the immunohistochemical study, Avy mice were pretreated with the astrocyte metabolic inhibitor fluorocitrate or phosphate-buffered saline (PBS) vehicle intracerebroventricularly (icv) followed 1 h later by Alexa568-leptin. Confocal microscopy showed that fluorocitrate pretreatment reduced astrocytic uptake of Alexa568-leptin 30 min a...

  20. Increased insulin and leptin sensitivity in mice lacking acyl CoA:diacylglycerol acyltransferase 1

    OpenAIRE

    Chen, Hubert C.; Smith, Steven J.; Ladha, Zuleika; Jensen, Dalan R.; Ferreira, Luis D.; Pulawa, Leslie K.; McGuire, James G.; Pitas, Robert E.; Robert H Eckel; Farese, Robert V.

    2002-01-01

    Acyl coenzyme A:diacylglycerol acyltransferase 1 (DGAT1) is one of two known DGAT enzymes that catalyze the final step in mammalian triglyceride synthesis. DGAT1-deficient mice are resistant to diet-induced obesity through a mechanism involving increased energy expenditure. Here we show that these mice have decreased levels of tissue triglycerides, as well as increased sensitivity to insulin and to leptin. Importantly, DGAT1 deficiency protects against insulin resistance and obesity in agouti...

  1. Palatability can drive feeding independent of AgRP neurons

    OpenAIRE

    Denis, Raphaël G.P.; Joly-Amado, Aurélie; Webber, Emily; Langlet, Fanny; Schaeffer, Marie; Padilla, Stéphanie L.; Cansell, Céline; Dehouck, Bénédicte; Castel, Julien; Delbès, Anne-Sophie; Martinez, Sarah; Lacombe, Amélie; Rouch, Claude; Kassis, Nadim; Fehrentz, Jean-Alain

    2015-01-01

    Feeding behavior is exquisitely regulated by homeostatic and hedonic neural substrates that integrate energy demand as well as the reinforcing and rewarding aspects of food. Understanding the net contribution of homeostatic and reward-driven feeding has become critical due to the ubiquitous source of energy-dense foods and the consequent obesity epidemic. Hypothalamic, agouti-related peptide-secreting neurons (AgRP neurons) provide primary orexigenic drive of homeostatic feeding. Using models...

  2. Hypothalamic Ceramide Levels Regulated by CPT1C Mediate the Orexigenic Effect of Ghrelin

    OpenAIRE

    Ramirez, S.; Martins, L.; Jacas, J.; Carrasco, P.; Pozo, M.; Clotet, J.; Serra, D.; Hegardt, F G; Dieguez, C.; Lopez, M.; Casals, N

    2013-01-01

    Recent data suggest that ghrelin exerts its orexigenic action through regulation of hypothalamic AMP-activated protein kinase pathway, leading to a decline in malonyl-CoA levels and desinhibition of carnitine palmitoyltransferase 1A (CPT1A), which increases mitochondrial fatty acid oxidation and ultimately enhances the expression of the orexigenic neuropeptides agouti-related protein (AgRP) and neuropeptide Y (NPY). However, it is unclear whether the brain-specific isoform CPT1C, which is loc...

  3. Dorsoventral patterning of the mouse coat by Tbx15.

    Directory of Open Access Journals (Sweden)

    Sophie I Candille

    2004-01-01

    Full Text Available Many members of the animal kingdom display coat or skin color differences along their dorsoventral axis. To determine the mechanisms that control regional differences in pigmentation, we have studied how a classical mouse mutation, droopy ear (de(H, affects dorsoventral skin characteristics, especially those under control of the Agouti gene. Mice carrying the Agouti allele black-and-tan (a(t normally have a sharp boundary between dorsal black hair and yellow ventral hair; the de(H mutation raises the pigmentation boundary, producing an apparent dorsal-to-ventral transformation. We identify a 216 kb deletion in de(H that removes all but the first exon of the Tbx15 gene, whose embryonic expression in developing mesenchyme correlates with pigmentary and skeletal malformations observed in de(H/de(H animals. Construction of a targeted allele of Tbx15 confirmed that the de(H phenotype was caused by Tbx15 loss of function. Early embryonic expression of Tbx15 in dorsal mesenchyme is complementary to Agouti expression in ventral mesenchyme; in the absence of Tbx15, expression of Agouti in both embryos and postnatal animals is displaced dorsally. Transplantation experiments demonstrate that positional identity of the skin with regard to dorsoventral pigmentation differences is acquired by E12.5, which is shortly after early embryonic expression of Tbx15. Fate-mapping studies show that the dorsoventral pigmentation boundary is not in register with a previously identified dermal cell lineage boundary, but rather with the limb dorsoventral boundary. Embryonic expression of Tbx15 in dorsolateral mesenchyme provides an instructional cue required to establish the future positional identity of dorsal dermis. These findings represent a novel role for T-box gene action in embryonic development, identify a previously unappreciated aspect of dorsoventral patterning that is widely represented in furred mammals, and provide insight into the mechanisms that underlie

  4. Analysis of genetic variants of coat colour loci and their influence on the coat colour phenotype and quantitative performance traits in the pig

    OpenAIRE

    Siebel, Krista

    2010-01-01

    The influence of four single coat colour loci (KIT, MC1R, TYR, ASP) on the coat colour phenotype and performance traits in the pig have been investigated in a resource population. The research revealed an unknown genotype for the white phenotype in the pig. The influence of the Agouti locus on the coat colour phenotype has been suggested. An influence of the coat colour loci KIT on growth performance traits and MC1R on body fatness could be demonstrated.

  5. Tachykinin-1 in the Central Nervous System Regulates Adiposity in Rodents

    OpenAIRE

    Trivedi, Chitrang; Shan, Xiaoye; Tung, Yi-Chun Loraine; Kabra, Dhiraj; Holland, Jenna; Amburgy, Sarah; Heppner, Kristy; Kirchner, Henriette; Giles S. H. Yeo; Perez-Tilve, Diego

    2015-01-01

    Ghrelin is a circulating hormone that targets the central nervous system to regulate feeding and adiposity. The best-characterized neural system that mediates the effects of ghrelin on energy balance involves the activation of neuropeptide Y/agouti-related peptide neurons, expressed exclusively in the arcuate nucleus of the hypothalamus. However, ghrelin receptors are expressed in other neuronal populations involved in the control of energy balance. We combined laser capture microdissection o...

  6. Linkage and segregation analysis of black and brindle coat color in domestic dogs.

    Science.gov (United States)

    Kerns, Julie A; Cargill, Edward J; Clark, Leigh Anne; Candille, Sophie I; Berryere, Tom G; Olivier, Michael; Lust, George; Todhunter, Rory J; Schmutz, Sheila M; Murphy, Keith E; Barsh, Gregory S

    2007-07-01

    Mutations of pigment type switching have provided basic insight into melanocortin physiology and evolutionary adaptation. In all vertebrates that have been studied to date, two key genes, Agouti and Melanocortin 1 receptor (Mc1r), encode a ligand-receptor system that controls the switch between synthesis of red-yellow pheomelanin vs. black-brown eumelanin. However, in domestic dogs, historical studies based on pedigree and segregation analysis have suggested that the pigment type-switching system is more complicated and fundamentally different from other mammals. Using a genomewide linkage scan on a Labrador x greyhound cross segregating for black, yellow, and brindle coat colors, we demonstrate that pigment type switching is controlled by an additional gene, the K locus. Our results reveal three alleles with a dominance order of black (K(B)) > brindle (k(br)) > yellow (k(y)), whose genetic map position on dog chromosome 16 is distinct from the predicted location of other pigmentation genes. Interaction studies reveal that Mc1r is epistatic to variation at Agouti or K and that the epistatic relationship between Agouti and K depends on the alleles being tested. These findings suggest a molecular model for a new component of the melanocortin signaling pathway and reveal how coat-color patterns and pigmentary diversity have been shaped by recent selection.

  7. Pigmentary switches in domestic animal species.

    Science.gov (United States)

    Klungland, H; Vage, D I

    2003-06-01

    Although homogeneous pigmentation usually is observed in wild animals, most domestic animal species display a wide variety of coat colors. In fur animals, the coat color is an important production trait, and in other species such as cattle and sheep, the coat color is a major breed characteristic. Variability in coat color is seen both within and between breeds, and makes domesticated species unique for studying gene function and gene regulation of loci affecting pigmentation. In several species, mutations in the MC1-R gene have been shown to cause the dominant expression of black pigment. In fox, alleles of both the agouti and the MC1-R gene could cause eumelanin synthesis. In addition, a nonepistatic interaction between MC1-R and agouti has been observed, resulting in several different coat color phenotypes expressing a mixture of red and black pigmentation. Also in cattle and sheep, amino acid substitutions within the MC1-R explain the dominant inheritance of black pigmentation. Unlike the constitutively activated MC1-R found in the Alaska silver fox, dominant variants of the MC1-R found in cattle and sheep seem to be completely dominant with no antagonizing effect of agouti. MC1-R variants with premature stop codons are widespread in several cattle populations, indicating that this well-conserved gene has no other fundamental function beside pigmentation. Other well-established breed characteristics include distinct coat color patterns in which the distribution of melanocytes, partly regulated by the c-kit gene, seems to be involved.

  8. Linkage and Segregation Analysis of Black and Brindle Coat Color in Domestic Dogs

    Science.gov (United States)

    Kerns, Julie A.; Cargill, Edward J.; Clark, Leigh Anne; Candille, Sophie I.; Berryere, Tom G.; Olivier, Michael; Lust, George; Todhunter, Rory J.; Schmutz, Sheila M.; Murphy, Keith E.; Barsh, Gregory S.

    2007-01-01

    Mutations of pigment type switching have provided basic insight into melanocortin physiology and evolutionary adaptation. In all vertebrates that have been studied to date, two key genes, Agouti and Melanocortin 1 receptor (Mc1r), encode a ligand-receptor system that controls the switch between synthesis of red–yellow pheomelanin vs. black–brown eumelanin. However, in domestic dogs, historical studies based on pedigree and segregation analysis have suggested that the pigment type-switching system is more complicated and fundamentally different from other mammals. Using a genomewide linkage scan on a Labrador × greyhound cross segregating for black, yellow, and brindle coat colors, we demonstrate that pigment type switching is controlled by an additional gene, the K locus. Our results reveal three alleles with a dominance order of black (KB) > brindle (kbr) > yellow (ky), whose genetic map position on dog chromosome 16 is distinct from the predicted location of other pigmentation genes. Interaction studies reveal that Mc1r is epistatic to variation at Agouti or K and that the epistatic relationship between Agouti and K depends on the alleles being tested. These findings suggest a molecular model for a new component of the melanocortin signaling pathway and reveal how coat-color patterns and pigmentary diversity have been shaped by recent selection. PMID:17483404

  9. Agent-based modeling for the landuse change of hunter-gather societies and the impacts on biodiversity in Guyana

    Science.gov (United States)

    Iwamura, T.; Fragoso, J.; Lambin, E.

    2012-12-01

    The interactions with animals are vital to the Amerindian, indigenous people, of Rupunini savannah-forest in Guyana. Their connections extend from basic energy and protein resource to spiritual bonding through "paring" to a certain animal in the forest. We collected extensive dataset of 23 indigenous communities for 3.5 years, consisting 9900 individuals from 1307 households, as well as animal observation data in 8 transects per communities (47,000 data entries). In this presentation, our research interest is to model the driver of land use change of the indigenous communities and its impacts on the ecosystem in the Rupunini area under global change. Overarching question we would like to answer with this program is to find how and why "tipping-point" from hunting gathering society to the agricultural society occurs in the future. Secondary question is what is the implication of the change to agricultural society in terms of biodiversity and carbon stock in the area, and eventually the well-being of Rupunini people. To answer the questions regarding the society shift in agriculture activities, we built as simulation with Agent-Based Modeling (Multi Agents Simulation). We developed this simulation by using Netlogo, the programming environment specialized for spatially explicit agent-based modeling (ABM). This simulation consists of four different process in the Rupunini landscape; forest succession, animal population growth, hunting of animals, and land clearing for agriculture. All of these processes are carried out by a set of computational unit, called "agents". In this program, there are four types of agents - patches, villages, households, and animals. Here, we describe the impacts of hunting on the biodiversity based on actual demographic data from one village named Crush Water. Animal population within the hunting territory of the village stabilized but Agouti/Paca dominates the landscape with little population of armadillos and peccaries. White-tailed deers

  10. Ecological relationships of meso-scale distribution in 25 neotropical vertebrate species.

    Directory of Open Access Journals (Sweden)

    Lincoln José Michalski

    Full Text Available Vertebrates are a vital ecological component of Amazon forest biodiversity. Although vertebrates are a functionally important part of various ecosystem services they continue to be threatened by anthropogenic impacts throughout the Amazon. Here we use a standardized, regularly spaced arrangement of camera traps within 25km2 to provide a baseline assessment of vertebrate species diversity in a sustainable use protected area in the eastern Brazilian Amazon. We examined seasonal differences in the per species encounter rates (number of photos per camera trap and number of cameras with photos. Generalized linear models (GLMs were then used to examine the influence of five variables (altitude, canopy cover, basal area, distance to nearest river and distance to nearest large river on the number of photos per species and on functional groups. GLMs were also used to examine the relationships between large predators [Jaguar (Panthera onca and Puma (Puma concolor] and their prey. A total of 649 independent photos of 25 species were obtained from 1,800 camera trap days (900 each during wet and dry seasons. Only ungulates and rodents showed significant seasonal differences in the number of photos per camera. The number of photos differed between seasons for only three species (Mazama americana, Dasyprocta leporina and Myoprocta acouchy all of which were photographed more (3 to 10 fold increase during the wet season. Mazama americana was the only species where a significant difference was found in occupancy, with more photos in more cameras during the wet season. For most groups and species variation in the number of photos per camera was only explained weakly by the GLMs (deviance explained ranging from 10.3 to 54.4%. Terrestrial birds (Crax alector, Psophia crepitans and Tinamus major and rodents (Cuniculus paca, Dasyprocta leporina and M. acouchy were the notable exceptions, with our GLMs significantly explaining variation in the distribution of all

  11. Mitigación de daños provocados por fauna silvestre en cultivos agrícolas en un bosque montano de Bolivia

    Directory of Open Access Journals (Sweden)

    Eddy Pérez L.

    2014-12-01

    Full Text Available El daño causado por fauna silvestre en cultivos agrícolas es una de las causas principales de conflicto dentro y fuera de áreas protegidas. Para un adecuado manejo del conflicto se requieren evaluaciones del daño y de la aplicación de distintos métodos de mitigación. El objetivo del trabajo fue evaluar la efectividad de prácticas agroculturales y cacería de control, para reducir daños por vertebrados silvestres en cultivos agrícolas anuales en el PN ANMI Cotapata. Se trabajó en siete parcelas con prácticas agroculturales, cuatro parcelas con cacería de control y cinco parcelas control, registrándose el tipo y densidad de cultivo, frecuencia de visitas de especies dañinas a huelleros, plantación perdida, especies responsables y biomasa de cosecha. Los resultados muestran que las especies más frecuentes fueron: Dasyprocta sp. y Dasypus novemcinctus, siendo estas 1.6 veces más frecuentes en parcelas con prácticas agroculturales. En promedio se perdió 7.3% de la plantación en parcelas agroculturales, 4.6% en parcelas sujetas a cacería de control, y 27.6% en parcelas control. Las principales especies responsables de las pérdidas fueron: P. tajacu, seguido por Dasyprocta sp. y S. apella. A través de estas estrategias de manejo, redujo las pérdidas en >50%, con lo cual se considera que los métodos puestos a prueba son útiles y se recomienda utilizarlos a gran escala con la consideración de que podría ser necesario innovar cada cierto tiempo, pues los animales silvestres tienden a acostumbrarse a los métodos de ahuyentamiento en ejecución.

  12. Ecological Relationships of Meso-Scale Distribution in 25 Neotropical Vertebrate Species

    Science.gov (United States)

    Michalski, Lincoln José; Norris, Darren; de Oliveira, Tadeu Gomes; Michalski, Fernanda

    2015-01-01

    Vertebrates are a vital ecological component of Amazon forest biodiversity. Although vertebrates are a functionally important part of various ecosystem services they continue to be threatened by anthropogenic impacts throughout the Amazon. Here we use a standardized, regularly spaced arrangement of camera traps within 25km2 to provide a baseline assessment of vertebrate species diversity in a sustainable use protected area in the eastern Brazilian Amazon. We examined seasonal differences in the per species encounter rates (number of photos per camera trap and number of cameras with photos). Generalized linear models (GLMs) were then used to examine the influence of five variables (altitude, canopy cover, basal area, distance to nearest river and distance to nearest large river) on the number of photos per species and on functional groups. GLMs were also used to examine the relationships between large predators [Jaguar (Panthera onca) and Puma (Puma concolor)] and their prey. A total of 649 independent photos of 25 species were obtained from 1,800 camera trap days (900 each during wet and dry seasons). Only ungulates and rodents showed significant seasonal differences in the number of photos per camera. The number of photos differed between seasons for only three species (Mazama americana, Dasyprocta leporina and Myoprocta acouchy) all of which were photographed more (3 to 10 fold increase) during the wet season. Mazama americana was the only species where a significant difference was found in occupancy, with more photos in more cameras during the wet season. For most groups and species variation in the number of photos per camera was only explained weakly by the GLMs (deviance explained ranging from 10.3 to 54.4%). Terrestrial birds (Crax alector, Psophia crepitans and Tinamus major) and rodents (Cuniculus paca, Dasyprocta leporina and M. acouchy) were the notable exceptions, with our GLMs significantly explaining variation in the distribution of all species

  13. Diversidad de mamíferos terrestres de talla grande y media de una selva subcaducifolia del noreste de Oaxaca, México Diversity of large and medium sized land mammals of a subcaducifolious tropical forest of north eastern of Oaxaca, Mexico

    Directory of Open Access Journals (Sweden)

    Gabriela Pérez-Irineo

    2012-03-01

    Full Text Available El estado de Oaxaca en el sureste de México alberga una biodiversidad extraordinaria. Sin embargo, las actividades humanas han propiciado alteraciones considerables, incluida la disminución de diferentes ambientes naturales, especialmente de los bosques tropicales; por ello es importante documentar la diversidad de estos ambientes, así como su respuesta a las transformaciones antropocéntricas. Este trabajo tiene como objetivo estimar la diversidad de mamíferos terrestres en una selva mediana en el noreste del estado de Oaxaca, México. Se recorrieron 3 senderos para la búsqueda de rastros, captura de organismos, avistamientos y fototrampeo de septiembre de 2007 a agosto de 2008. Se registraron 15 especies de 6 órdenes, 11 familias y 14 géneros, entre ellas 7 nuevas para la región. Las especies más abundantes fueron Nasua narica, Pecari tajacu, Dasyprocta mexicana, Cuniculus paca y Leopardus pardalis. A pesar de presentar un índice de diversidad bajo con respecto a otros estudios comparables, la presencia de especies consideradas en riesgo por la legislación mexicana, como L. pardalis, L. wiedii, Eira barbara y Tamandua mexicana hacen a la zona valiosa para la conservación de la diversidad en la región.The state of Oaxaca, in southeast Mexico is home to an extraordinary biodiversity. But human activities have led to significant changes, including reduction of different natural habitats, especially tropical forests, so it is important to document the diversity of these environments, and their response to the anthropocentric changes. Therefore, this study aimed to estimate the diversity of terrestrial mammals in a tropical forest in northeastern of the state of Oaxaca, Mexico. Three transects were walked to search for tracks, catches of organisms, sightings, and phototrapping from September 2007 to August 2008. There were recorded 15 species of 6 orders, 11 families, and 14 genera, 7 of this not previously known in the region. The

  14. Ecological relationships of meso-scale distribution in 25 neotropical vertebrate species.

    Science.gov (United States)

    Michalski, Lincoln José; Norris, Darren; de Oliveira, Tadeu Gomes; Michalski, Fernanda

    2015-01-01

    Vertebrates are a vital ecological component of Amazon forest biodiversity. Although vertebrates are a functionally important part of various ecosystem services they continue to be threatened by anthropogenic impacts throughout the Amazon. Here we use a standardized, regularly spaced arrangement of camera traps within 25km2 to provide a baseline assessment of vertebrate species diversity in a sustainable use protected area in the eastern Brazilian Amazon. We examined seasonal differences in the per species encounter rates (number of photos per camera trap and number of cameras with photos). Generalized linear models (GLMs) were then used to examine the influence of five variables (altitude, canopy cover, basal area, distance to nearest river and distance to nearest large river) on the number of photos per species and on functional groups. GLMs were also used to examine the relationships between large predators [Jaguar (Panthera onca) and Puma (Puma concolor)] and their prey. A total of 649 independent photos of 25 species were obtained from 1,800 camera trap days (900 each during wet and dry seasons). Only ungulates and rodents showed significant seasonal differences in the number of photos per camera. The number of photos differed between seasons for only three species (Mazama americana, Dasyprocta leporina and Myoprocta acouchy) all of which were photographed more (3 to 10 fold increase) during the wet season. Mazama americana was the only species where a significant difference was found in occupancy, with more photos in more cameras during the wet season. For most groups and species variation in the number of photos per camera was only explained weakly by the GLMs (deviance explained ranging from 10.3 to 54.4%). Terrestrial birds (Crax alector, Psophia crepitans and Tinamus major) and rodents (Cuniculus paca, Dasyprocta leporina and M. acouchy) were the notable exceptions, with our GLMs significantly explaining variation in the distribution of all species

  15. Further characterization of diabetes mellitus and body weight loss in males of the congenic mouse strain DDD.Cg-Ay

    OpenAIRE

    Suto, Jun-ichi; Satou, Kunio

    2014-01-01

    The Ay allele at the agouti locus causes obesity and promotes linear growth in mice. However, body weight gain stops between 16 and 17 weeks after birth, and then, body weight decreases gradually in DDD.Cg-Ay male mice. Body weight loss is a consequence of diabetes mellitus, which is genetically controlled mainly by a quantitative trait locus (QTL) on chromosome 4. This study aimed to further characterize diabetes mellitus and body weight loss in DDD.Cg-Ay males. The number of ?-cells was mar...

  16. Cellular and genetic analysis of mouse blastocyst development

    Energy Technology Data Exchange (ETDEWEB)

    Pedersen, R A; Spindle, A I

    1979-01-01

    The development of mouse embryos was studied by both cellular and genetic approaches. In the cellular analysis, determination of cell fate in blastocysts and in cell populations derived from them was studied in an attempt to estimate the time that these cells become committed to their fate. In the genetic analysis, existing mutations that are lethal to mouse embryos were used to discern essential features of early development. In this review, the timing of cell determination in the inner cell mass and the primary ectoderm, and the manifestation of defects in mouse embryos that are homozygous for the A/sup y/ allele of the agouti locus were considered.

  17. Molecular mechanism of agonism and inverse agonism in the melanocortin receptors: Zn(2+) as a structural and functional probe

    DEFF Research Database (Denmark)

    Holst, Birgitte; Schwartz, Thue W

    2003-01-01

    Among the rhodopsin-like 7TM receptors, the MC receptors are functionally unique because their high constitutive signaling activity is regulated not only by endogenous peptide agonists-MSH peptides-but also by endogenous inverse agonists, namely, the proteins agouti and AGRP. Moreover, the metal...... extracellular loop 2 is ultrashort because TM-IV basically connects directly into TM-V, whereas extracellular loop 3 appears to be held in a particular, constrained conformation by a putative, internal disulfide bridge. The interaction mode for the small and well-defined zinc-ion between a third, free Cys...

  18. Quantitative trait locus mapping of genes associated with vacuolation in the adrenal X-zone of the DDD/Sgn inbred mouse.

    Science.gov (United States)

    Suto, Jun-Ichi

    2012-11-06

    Adrenal gland of mice contains a transient zone between the adrenal cortex and the adrenal medulla: the X-zone. There are clear strain differences in terms of X-zone morphology. Nulliparous females of the inbred mouse DDD strain develop adrenal X-zones containing exclusively vacuolated cells, whereas females of the inbred mouse B6 strain develop X-zones containing only non-vacuolated cells. The X-zone vacuolation is a physiologic process associated with the X-zone degeneration and is tightly regulated by genetic factors. Identification of the genetic factors controlling such strain differences should help analyze the X-zone function. In this study, a quantitative trait locus (QTL) analysis for the extent of X-zone vacuolation was performed for two types of F2 female mice: F2Ay mice (F2 mice with the Ay allele) and F2 non-Ay mice (F2 mice without the Ay allele). These were produced by crossing B6 females and DDD.Cg-Ay males. DDD.Cg-Ay is a congenic mouse strain for the Ay allele at the agouti locus and is used for this study because a close association between the X-zone morphology and the agouti locus genotype has been suggested. The Ay allele is dominant and homozygous lethal; therefore, living Ay mice are invariably heterozygotes. Single QTL scans identified significant QTLs on chromosomes 1, 2, 6, and X for F2 non-Ay mice, and on chromosomes 2, 6, and 12 for F2Ay mice. The QTL on chromosome 2 was considered to be because of the agouti locus, which has been suggested to be associated with X-zone vacuolation. A significant QTL that interacted with the agouti locus was identified on chromosome 8. The extent of X-zone vacuolation in DDD females was controlled by multiple genes with complex interactions. The murine X-zone is considered analogous structure to the human fetal zone. Therefore, the results of this study will aid in understanding function of not only of the X-zone but also of the human fetal zone. Identifying the genes responsible for the QTLs will be

  19. Quantitative trait locus mapping of genes associated with vacuolation in the adrenal X-zone of the DDD/Sgn inbred mouse

    Directory of Open Access Journals (Sweden)

    Suto Jun-ichi

    2012-11-01

    Full Text Available Abstract Background Adrenal gland of mice contains a transient zone between the adrenal cortex and the adrenal medulla: the X-zone. There are clear strain differences in terms of X-zone morphology. Nulliparous females of the inbred mouse DDD strain develop adrenal X-zones containing exclusively vacuolated cells, whereas females of the inbred mouse B6 strain develop X-zones containing only non-vacuolated cells. The X-zone vacuolation is a physiologic process associated with the X-zone degeneration and is tightly regulated by genetic factors. Identification of the genetic factors controlling such strain differences should help analyze the X-zone function. In this study, a quantitative trait locus (QTL analysis for the extent of X-zone vacuolation was performed for two types of F2 female mice: F2Ay mice (F2 mice with the Ay allele and F2 non-Ay mice (F2 mice without the Ay allele. These were produced by crossing B6 females and DDD.Cg-Ay males. DDD.Cg-Ay is a congenic mouse strain for the Ay allele at the agouti locus and is used for this study because a close association between the X-zone morphology and the agouti locus genotype has been suggested. The Ay allele is dominant and homozygous lethal; therefore, living Ay mice are invariably heterozygotes. Results Single QTL scans identified significant QTLs on chromosomes 1, 2, 6, and X for F2 non-Ay mice, and on chromosomes 2, 6, and 12 for F2Ay mice. The QTL on chromosome 2 was considered to be because of the agouti locus, which has been suggested to be associated with X-zone vacuolation. A significant QTL that interacted with the agouti locus was identified on chromosome 8. Conclusions The extent of X-zone vacuolation in DDD females was controlled by multiple genes with complex interactions. The murine X-zone is considered analogous structure to the human fetal zone. Therefore, the results of this study will aid in understanding function of not only of the X-zone but also of the human fetal zone

  20. Hypothalamic Inflammation in Obesity, Insulin Resistance and Ageing

    OpenAIRE

    Tsaousidou, Eva

    2014-01-01

    In this study, the role of hypothalamic inflammation in obesity, insulin resistance and the regulation of the ageing process is investigated. Activation of c-Jun N-terminal kinase (JNK)1- and inhibitor of nuclear factor kappa-B kinase (IKK)2-dependent signalling plays a crucial role in the development of obesity-associated insulin and leptin resistance not only in peripheral tissues but also in the CNS. This study demonstrates that constitutive JNK1 activation in agouti-related peptide (AgRP)...

  1. Feeding effects of hypothalamic injection of melanocortin 4 receptor ligands.

    Science.gov (United States)

    Giraudo, S Q; Billington, C J; Levine, A S

    1998-11-02

    It has been reported that intraventricular administration of the melanocortin 4 receptor (MC4-R) agonist MT II and antagonist SHU9119 alter food intake. We found that MT II and SHU9119 have extremely potent effects on feeding when injected in the paraventricular nucleus (PVN), a site where MC4-R gene expression is very high. Our finding provides direct evidence that MC4-R signaling is important in mediating food intake and that melanocortin neurons in the PVN exert a tonic inhibition of feeding behavior. Chronic disruption of this inhibitory signal is a possible explanation of the agouti-obesity syndrome.

  2. STEAROYL-CoA DESATURASE-1 DEFICIENCY ATTENUATES OBESITY AND INSULIN RESISTANCE IN LEPTIN-RESISTANT OBESE MICE

    OpenAIRE

    Miyazaki, Makoto; Sampath, Harini; Liu, Xueqing; Flowers, Matthew T; Chu, Kiki; Dobrzyn, Agnieszka; Ntambi, James M.

    2009-01-01

    Obesity and adiposity greatly increase the risk for secondary conditions such as insulin resistance. Mice deficient in the enzyme stearoyl-CoA desaturase-1 (SCD1) are lean and protected from diet-induced obesity and insulin resistance. In order to determine the effect of SCD1 deficiency on various mouse models of obesity, we introduced a global deletion of the Scd1 gene into leptin-deficient ob/ob mice, leptin-resistant Agouti (Ay/a) mice, and high-fat diet-fed obese (DIO) mice. SCD1 deficien...

  3. Development of a novel pink-eyed dilution mouse model showing progressive darkening of the eyes and coat hair with aging

    OpenAIRE

    ISHIKAWA, AKIRA; SUGIYAMA, Makoto; Hondo, Eiichi; Kinoshita, Keiji; YAMAGISHI, Yuki

    2015-01-01

    Oca2p-cas (oculocutaneous albinism II; pink-eyed dilution castaneus) is a coat color mutant gene on mouse chromosome 7 that arose spontaneously in wild Mus musculus castaneus mice. Mice homozygous for Oca2p-cas usually exhibit pink eyes and gray coat hair on the non-agouti genetic background, and this ordinary phenotype remains unchanged throughout life. During breeding of a mixed strain carrying this gene on the C57BL/6J background, we discovered a novel spontaneous mutation that causes dark...

  4. Identification and assessment of products of biodiversity with commercial potential in an organized group of producers in the area of influence of the Eco-Archeological Corridor in the South of Huila

    Directory of Open Access Journals (Sweden)

    Martha Cecilia Vinasco Guzmán

    2011-10-01

    Full Text Available In Colombia, despite the wide biodiversity, efforts to find the products that may be involved in bio-activities have been inadequate and communities have not been involved with this proposal for economic and social development. To contribute to the development of these initiatives, an investigation over three groups belonging to the Mashiramo Corporation (Pitalito’s municipalities of San Agustin and Acevedo was carried out since February to September 2010, in seeking of biodiversity products with commercial potential in the south area of Huila, using the methodology of Market Analysis and Development (MA & D. In phase 1, 17 products were selected and classified into 4 groups: forest products and byproducts (species of orchids, native flowers, forest species and seeds, Zoo-breeding (lepidopteron fauna, wild and hydro biological resources, native foods (two legume species and products and services (ecotourism, environmental services and sale of handicrafts. In phase 2 (identification of products, markets and ways of marketing 5 products were analized: ecotourism, incipient handicrafts, black fish farming (Astroblepus chapmani, a nursery of native forest species and Guatin Zoo-breeding (Dasyprocta punctata. In the third phase, the plan was formulated for ecotourism business with emphasis on bird watching. It was concluded that methodological appropriation is needed by the beneficiary community to ensure the development of activities to learn to make decisions based on market data and not for creating false expectations that generate negative experiences in communities.

  5. Hunting and use of terrestrial fauna used by Caiçaras from the Atlantic Forest coast (Brazil

    Directory of Open Access Journals (Sweden)

    Alves Rômulo RN

    2009-11-01

    Full Text Available Abstract Background The Brazilian Atlantic Forest is considered one of the hotspots for conservation, comprising remnants of rain forest along the eastern Brazilian coast. Its native inhabitants in the Southeastern coast include the Caiçaras (descendants from Amerindians and European colonizers, with a deep knowledge on the natural resources used for their livelihood. Methods We studied the use of the terrestrial fauna in three Caiçara communities, through open-ended interviews with 116 native residents. Data were checked through systematic observations and collection of zoological material. Results The dependence on the terrestrial fauna by Caiçaras is especially for food and medicine. The main species used are Didelphis spp., Dasyprocta azarae, Dasypus novemcinctus, and small birds (several species of Turdidae. Contrasting with a high dependency on terrestrial fauna resources by native Amazonians, the Caiçaras do not show a constant dependency on these resources. Nevertheless, the occasional hunting of native animals represents a complimentary source of animal protein. Conclusion Indigenous or local knowledge on native resources is important in order to promote local development in a sustainable way, and can help to conserve biodiversity, particularly if the resource is sporadically used and not commercially exploited.

  6. CURRENT STATE OF CONSERVATION, FIRST PHOTOGRAPHIC RECORD AND POPULATION ESTIMATION OF THE COASTAL JAGUAR (Panthera onca centralis AND RECORDS OF COMPANION FAUNA OF MEDIUM-SIZED AND HIGHER MAMMALS IN THE PROTECTED FOREST CERRO BLANCO OF THE CHONGÓN COLONCHE MOUNTAIN RANGE, GUAYAQUIL – ECUADOR

    Directory of Open Access Journals (Sweden)

    Miguel Saavedra

    2013-12-01

    Full Text Available The Chongón-Colonche Mountain Range is important for their goods and environmental services, its high biodiversity, and being one of the few coastal regions of Ecuador, which still houses the coastal Jaguar Panthera onca centralis. In the Forest Protector Cerro Blanco (BPCB, last Southeast extension of the mountain chain, it was developed the field research through the data collection with direct and indirect medium-sized and higher mammals’ records. Besides a Cuddeback Digital camera trap was used, by selecting a sampling point within a probable route of the jaguar. Inspections in a nearby quarry were made to observe traces of major feline registries. The same consolidated past sightings or evidence of witnesses which complemented the study for the determination of the status of the species in the BPCB. The study showed indirect and direct records of white-tailed deer, peccaries, raccoons, agoutis, wild rabbits, howler monkeys, Capuchin white or monkeys, agouti, bears Anteaters and Jaguars from the coast for which it is considered that the BPCB is probably a meeting place between two individuals; however, it is important to note that the results presented are preliminary.

  7. Two important systems in energy homeostasis: melanocortins and melanin-concentrating hormone.

    Science.gov (United States)

    Tritos, N A; Maratos-Flier, E

    1999-10-01

    Our understanding of the regulation of appetite and energy balance has advanced significantly over the past decade as several peptides, centrally or peripherally expressed, have been characterized and shown to profoundly influence food intake and energy expenditure. (1)The growing number of putative appetite-regulating neuropeptides includes peptides that are orexigenic (appetite-stimulating) signals and anorectic peptides. Neuropeptide Y (NPY), melanin concentrating hormone (MCH), orexins A and B, galanin, and agouti -related peptide (AgRP) all act to stimulate feeding while alpha-melanocyte stimulating hormone (alphaMSH), corticotropin releasing hormone (CRH), cholecystokinin (CCK), cocaine and amphetamine regulated transcript (CART), neurotensin, glucagon-like peptide 1 (GLP 1), and bombesin have anorectic actions.(1) Leptin, expressed in the periphery in white adipose tissue, acts in the CNS to modulate the expression of several of these hypothalamic peptides.(1) This creates a functional link between the adipose tissue and the brain that translates the information on body fat provided by leptin to input into energy balance regulating processes. In the current review we examine the significant role of the melanocortin system (alphaMSH, agouti and AgRP peptides, and their receptors and mahogany protein) and melanin concentrating hormone in the regulation of energy balance. Copyright 1999 Harcourt Publishers Ltd.

  8. Natural Genetic Variation Underlying Differences in Peromyscus Repetitive & Social/Aggressive Behaviors

    Science.gov (United States)

    Shorter, Kimberly R.; Owen, Amy; Anderson, Vanessa; Hall-South, April C.; Hayford, Samantha; Cakora, Patricia; Crossland, Janet P.; Georgi, Velina R. M.; Perkins, Amy; Kelly, Sandra J.; Felder, Michael R.; Vrana, Paul B.

    2014-01-01

    Peromyscus maniculatus (BW) and P. polionotus (PO) are interfertile North American species that differ in many characteristics. For example, PO exhibit monogamy and BW animals are susceptible to repetitive behaviors and thus a model for neurobehavioral disorders such as Autism. We analyzed these two stocks as well as their hybrids, a BW YPO consomic line (previously shown to alter glucose homeostasis) and a natural P. maniculatus agouti variant (ANb = wide band agouti). We show that PO animals engage in far less repetitive behavior than BW animals, that this trait is dominant, and that trait distribution in both species is bi-modal. The ANb allele also reduces such behaviors, particularly in females. PO, F1, and ANb animals all dig significantly more than BW. Increased self-grooming is also a PO dominant trait, and there is a bimodal trait distribution in all groups except BW. The inter-stock differences in self-grooming are greater between males, and the consomic data suggest the Y chromosome plays a role. The monogamous PO animals engage in more social behavior than BW; hybrid animals exhibit intermediate levels. Surprisingly, ANb animals are also more social than BW animals, although ANb interactions led to aggressive interactions at higher levels than any other group. PO animals exhibited the lowest incidence of aggressive behaviors, while the hybrids exhibited BW levels. Thus this group exhibits natural, genetically tractable variation in several biomedically relevant traits. PMID:24407381

  9. Natural genetic variation underlying differences in Peromyscus repetitive and social/aggressive behaviors.

    Science.gov (United States)

    Shorter, Kimberly R; Owen, Amy; Anderson, Vanessa; Hall-South, April C; Hayford, Samantha; Cakora, Patricia; Crossland, Janet P; Georgi, Velina R M; Perkins, Amy; Kelly, Sandra J; Felder, Michael R; Vrana, Paul B

    2014-03-01

    Peromyscus maniculatus (BW) and P. polionotus (PO) are interfertile North American species that differ in many characteristics. For example, PO exhibit monogamy and BW animals are susceptible to repetitive behaviors and thus a model for neurobehavioral disorders such as Autism. We analyzed these two stocks as well as their hybrids, a BW Y(PO) consomic line (previously shown to alter glucose homeostasis) and a natural P. maniculatus agouti variant (A(Nb) = wide band agouti). We show that PO animals engage in far less repetitive behavior than BW animals, that this trait is dominant, and that trait distribution in both species is bi-modal. The A(Nb) allele also reduces such behaviors, particularly in females. PO, F1, and A(Nb) animals all dig significantly more than BW. Increased self-grooming is also a PO dominant trait, and there is a bimodal trait distribution in all groups except BW. The inter-stock differences in self-grooming are greater between males, and the consomic data suggest the Y chromosome plays a role. The monogamous PO animals engage in more social behavior than BW; hybrid animals exhibit intermediate levels. Surprisingly, A(Nb) animals are also more social than BW animals, although A(Nb) interactions led to aggressive interactions at higher levels than any other group. PO animals exhibited the lowest incidence of aggressive behaviors, while the hybrids exhibited BW levels. Thus this group exhibits natural, genetically tractable variation in several biomedically relevant traits.

  10. Whole-Genome Sequences of DA and F344 Rats with Different Susceptibilities to Arthritis, Autoimmunity, Inflammation and Cancer

    Science.gov (United States)

    Guo, Xiaosen; Brenner, Max; Zhang, Xuemei; Laragione, Teresina; Tai, Shuaishuai; Li, Yanhong; Bu, Junjie; Yin, Ye; Shah, Anish A.; Kwan, Kevin; Li, Yingrui; Jun, Wang; Gulko, Pércio S.

    2013-01-01

    DA (D-blood group of Palm and Agouti, also known as Dark Agouti) and F344 (Fischer) are two inbred rat strains with differences in several phenotypes, including susceptibility to autoimmune disease models and inflammatory responses. While these strains have been extensively studied, little information is available about the DA and F344 genomes, as only the Brown Norway (BN) and spontaneously hypertensive rat strains have been sequenced to date. Here we report the sequencing of the DA and F344 genomes using next-generation Illumina paired-end read technology and the first de novo assembly of a rat genome. DA and F344 were sequenced with an average depth of 32-fold, covered 98.9% of the BN reference genome, and included 97.97% of known rat ESTs. New sequences could be assigned to 59 million positions with previously unknown data in the BN reference genome. Differences between DA, F344, and BN included 19 million positions in novel scaffolds, 4.09 million single nucleotide polymorphisms (SNPs) (including 1.37 million new SNPs), 458,224 short insertions and deletions, and 58,174 structural variants. Genetic differences between DA, F344, and BN, including high-impact SNPs and short insertions and deletions affecting >2500 genes, are likely to account for most of the phenotypic variation between these strains. The new DA and F344 genome sequencing data should facilitate gene discovery efforts in rat models of human disease. PMID:23695301

  11. Preliminary study on MC1R polymorphism in some cattle breeds raised in Italy

    Directory of Open Access Journals (Sweden)

    C. Renieri

    2011-03-01

    Full Text Available Most of the Western European cattle breeds consist of standardised breeds with a definite coat colour (Renieri et al., 1984. Thus coat colour could be useful to detect genetic markers for cattle breed identification. In cattle the pigmentation is determined by the distribution of two pigments: eu- and pheomelanin, producing brown or black and red to yellow pigmentation respectively. Tyrosinase, the rate-limiting enzyme involved in the synthesis of both melanins, is regulated by the melanocyte stimulating hormone (αMSH. This hormone and several other melanotropic peptides stimulate melanin formation in melanocytes by binding to the melanocortin-1-receptor (MC1R, a G-protein-coupled receptor encoded by the Extension gene (Robbins et al., 1993. In addition, the amounts of eu- and pheomelanin in the melanocyte are controlled by the agouti gene encoding the Agouti Signal Protein (ASP, that acts as an antagonist of MSH signalling through the MC1R, even if its mechanism of action is controversial (Furumura et al., 1998..........

  12. The prediction role of indexes of circulating adipokines for common anthropometric and nutritional characteristics of obesity in the obese Central European population.

    Science.gov (United States)

    Bienertová-Vašků, Julie; Novák, Jan; Zlámal, Filip; Forejt, Martin; Havlenová, Soňa; Jackowská, Aneta; Tomandl, Josef; Tomandlová, Marie; Šplíchal, Zbyněk; Vašků, Anna

    2014-04-01

    This study was designed to investigate the relationship between 8 selected adipokines (leptin, leptin receptor, adiponectin, agouti-related peptide, omentin, visfatin, adipsin and resistin), dietary composition and anthropometric parameters found in the Central European obese population. A total of 65 unrelated obese Central European Caucasian individuals were recruited for the study. Phenotypic measurements included weight, height, BMI, lean body mass, fat mass, body fat, waist and hip circumference, waist-hip ratio (WHR) and skinfold thickness. Participants completed standardized self-reported 7-day food records. Plasma levels of leptin, leptin receptor, adiponectin, agouti-related peptide (AgRP), resistin, adipsin, omentin and visfatin were examined using ELISA. Multiple associations (weight, height, percentage of body fat, waist circumference, hip circumference, WHR and sum of skinfold thickness) with the circulation levels of the investigated adipokines were identified. Leptin-Leptin receptor (L-LR) levels were found to correlate with total energy intake and macronutrients while adipsin was found to strongly correlate with multiple adipokines. Furthermore, the L-LR index was found to constitute a more accurate description of the relationship between BMI and body weight than individual measurements and the Ag-LR index was found to strongly correlate with both anthropometric and dietary characteristics. Following confirmation on larger population samples and on samples of different ethnicities, the reported adipokine indexes could become a useful tool for estimating nutritional status and predicting the body composition of specific patient groups. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Involvement of progranulin in hypothalamic glucose sensing and feeding regulation.

    Science.gov (United States)

    Kim, Hyun-Kyong; Shin, Mi-Seon; Youn, Byung-Soo; Namkoong, Churl; Gil, So Young; Kang, Gil Myoung; Yu, Ji Hee; Kim, Min-Seon

    2011-12-01

    Progranulin (PGRN) is a secreted glycoprotein with multiple biological functions, including modulation of wound healing and inflammation. Hypothalamic PGRN has been implicated in the development of sexual dimorphism. In the present study, a potential role for PGRN in the hypothalamic regulation of appetite and body weight was investigated. In adult rodents, PGRN was highly expressed in periventricular tanycytes and in hypothalamic neurons, which are known to contain glucose-sensing machinery. Hypothalamic PGRN expression levels were decreased under low-energy conditions (starvation and 2-deoxy-D-glucose administration) but increased under high-energy condition (postprandially). Intracerebrovetricular administration of PGRN significantly suppressed nocturnal feeding as well as hyperphagia induced by 2-deoxyglucose, neuropeptide Y, and Agouti-related peptide. Moreover, the inhibition of hypothalamic PGRN expression or action increased food intake and promoted weight gain, suggesting that endogenous PGRN functions as an appetite suppressor in the hypothalamus. Investigation of the mechanism of action revealed that PGRN diminished orexigenic neuropeptide Y and Agouti-related peptide production but stimulated anorexigenic proopiomelanocortin production, at least in part through the regulation of hypothalamic AMP-activated protein kinase. Notably, PGRN was also expressed in hypothalamic microglia. In diet-induced obese mice, microglial PGRN expression was increased, and the anorectic response to PGRN was blunted. These findings highlight a physiological role for PGRN in hypothalamic glucose-sensing and appetite regulation. Alterations in hypothalamic PGRN production or action may be linked to appetite dysregulation in obesity.

  14. Brain innate immunity regulates hypothalamic arcuate neuronal activity and feeding behavior.

    Science.gov (United States)

    Reis, Wagner L; Yi, Chun-Xia; Gao, Yuanqing; Tschöp, Mathias H; Stern, Javier E

    2015-04-01

    Hypothalamic inflammation, involving microglia activation in the arcuate nucleus (ARC), is proposed as a novel underlying mechanism in obesity, insulin and leptin resistance. However, whether activated microglia affects ARC neuronal activity, and consequently basal and hormonal-induced food intake, is unknown. We show that lipopolysaccharide, an agonist of the toll-like receptor-4 (TLR4), which we found to be expressed in ARC microglia, inhibited the firing activity of the majority of orexigenic agouti gene-related protein/neuropeptide Y neurons, whereas it increased the activity of the majority of anorexigenic proopiomelanocortin neurons. Lipopolysaccharide effects in agouti gene-related protein/neuropeptide Y (but not in proopiomelanocortin) neurons were occluded by inhibiting microglia function or by blocking TLR4 receptors. Finally, we report that inhibition of hypothalamic microglia altered basal food intake, also preventing central orexigenic responses to ghrelin. Our studies support a major role for a TLR4-mediated microglia signaling pathway in the control of ARC neuronal activity and feeding behavior.

  15. The melanocortin receptors: lessons from knockout models.

    Science.gov (United States)

    Butler, A A; Cone, R D

    2002-01-01

    Identifying the role of the melanocortin system in regulating energy homeostasis has relied on both genetic and pharmacological studies. The key findings included 1) that the coat color phenotype in the lethal yellow (A(Y)/a) mouse is due to antagonism of the melanocortin-1 receptor (MC1R) by the agouti gene product; 2) the MC3R and MC4R are expressed in CNS centers involved in energy homeostasis, and 3) the combined results of pharmacological studies showing that agouti is an antagonist of the MC4R and transgenic studies showing that inhibition or loss of the MC4R recapitulate the lethal yellow phenotype. Pro-opiomelanocortin (POMC), MC3R, and MC4R knockouts are obese and are now being used to further analyze melanocortin receptor function. The obesity phenotype observed in the MC3R and MC4R knockouts (KO) differ markedly. MC4RKO mice are hyperphagic, do not regulate pathways that increase energy expenditure (diet-induced thermogenesis) and physical activity in response to hyperphagia, and can develop type 2 diabetes. In contrast, MC3R deficient mice are not hyperphagic, have a normal metabolic response to increased energy consumption, and do not develop diabetes. The mechanism underlying the increased adiposity in the MC3R knockout remains unclear, but might be related to changes in nutrient partitioning or physical activity.

  16. Whole-genome sequences of DA and F344 rats with different susceptibilities to arthritis, autoimmunity, inflammation and cancer.

    Science.gov (United States)

    Guo, Xiaosen; Brenner, Max; Zhang, Xuemei; Laragione, Teresina; Tai, Shuaishuai; Li, Yanhong; Bu, Junjie; Yin, Ye; Shah, Anish A; Kwan, Kevin; Li, Yingrui; Jun, Wang; Gulko, Pércio S

    2013-08-01

    DA (D-blood group of Palm and Agouti, also known as Dark Agouti) and F344 (Fischer) are two inbred rat strains with differences in several phenotypes, including susceptibility to autoimmune disease models and inflammatory responses. While these strains have been extensively studied, little information is available about the DA and F344 genomes, as only the Brown Norway (BN) and spontaneously hypertensive rat strains have been sequenced to date. Here we report the sequencing of the DA and F344 genomes using next-generation Illumina paired-end read technology and the first de novo assembly of a rat genome. DA and F344 were sequenced with an average depth of 32-fold, covered 98.9% of the BN reference genome, and included 97.97% of known rat ESTs. New sequences could be assigned to 59 million positions with previously unknown data in the BN reference genome. Differences between DA, F344, and BN included 19 million positions in novel scaffolds, 4.09 million single nucleotide polymorphisms (SNPs) (including 1.37 million new SNPs), 458,224 short insertions and deletions, and 58,174 structural variants. Genetic differences between DA, F344, and BN, including high-impact SNPs and short insertions and deletions affecting >2500 genes, are likely to account for most of the phenotypic variation between these strains. The new DA and F344 genome sequencing data should facilitate gene discovery efforts in rat models of human disease.

  17. Melanocortin receptor accessory protein 2 (MRAP2) interplays with the zebrafish melanocortin 1 receptor (MC1R) but has no effect on its pharmacological profile.

    Science.gov (United States)

    Cortés, Raúl; Agulleiro, Maria Josep; Navarro, Sandra; Guillot, Raúl; Sánchez, Elisa; Cerdá-Reverter, José Miguel

    2014-05-15

    The melanocortin system is probably one of the most complex hormonal systems since it integrates agonist, encoded in the proopiomelanocortin precursor, endogenous antagonist, agouti signaling protein and agouti-related protein, five different G-protein coupled receptors and two accessory proteins. These accessory proteins interact with melanocortin receptors to allow traffic to the plasma membrane or to regulate the pharmacological profile. The MC1R fill the extension locus, which is primarily responsible for the regulation of pigmentation. In zebrafish, both MC1R and MRAP2 system are expressed in the skin. We demonstrate that zebrafish MC1R physically, or closely, interacts with the MRAP2 system, although this interaction did not result in modification of the studied pharmacological profile. However, progressive fasting induced skin darkening but also an upregulation of the MRAP2 expression in the skin, suggesting an unknown role for MRAP2a that could involve receptor desensitization processes. We also demonstrate that crowding stress induces skin darkening and a downregulation of MC1R expression in the skin. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Anatomical description of arterial segments in the crab-eating raccoon kidney (Procyon cancrivorus

    Directory of Open Access Journals (Sweden)

    Natane Barbosa Barcelos

    2012-06-01

    Full Text Available Crab-eating raccoon is a middle-sized animal with a long tail, which is yellowish and has a black and ornate tip, presenting from 5 to 10 dark and yellow rings. The specimens live in equatorial and tropical forests, always close to rivers, swamps, marshes, and mangroves. Two specimens of Procyon cancrivorus were used, both killed by accident and, later on, sent to the Anatomy Laboratory of Universidade Federal de Goias (UFG, in the Jatai campus, where, starting from the renal arteries, the arterial segments were dissected with the aid of a stereoscopic microscope. As a result, the renal arteries were always viewed in a single manner, bifurcating into dorsal and ventral segments, subdivided into ventro-cranial, ventro-medial-cranial, ventro-medial, ventromedial-caudal, ventro-caudal, dorso-cranial, dorso-medial-cranial, dorso-medial, dorso-medial-caudal, and dorso-caudal segments, also observed in rabbit, agouti, wild boar, and ovines. This study showed an arterial distribution pattern which is also identified in the right and left kidneys, the penetration site of renal arteries coincide with the findings in mouse and differ from those in rat, golden hamster, and agouti. According to the distribution and arrangement, the renal morphology of Procyon cancrivorus is similar to that found in pets and wild animals. The recognition of renal artery branches shows to be highly relevant both for surgical interventions and future investigations which enhance the knowledge on this species.

  19. Interpretation of the pharmacokinetics of ochratoxin A in blood plasma of rats, during and after acute or chronic ingestion.

    Science.gov (United States)

    Mantle, Peter G

    2008-05-01

    Experiments designed to reveal aspects of delivery of circulating ochratoxin A (OTA) to kidneys showed maximum plasma concentration within 3h of acute gavage, but this persisted for 4 days before decline. During long-term daily administration in feed, plasma values stabilised, proportional to dose and, for Fischer males, immediately followed an 8-10 day half-life upon ceasing OTA intake. In mature adult males, plasma OTA accumulated during the month after commencing daily intake of 100 microg. By comparison, in Dark Agouti males, lower steady state plasma values occurred and there was much shorter plasma OTA half-life (2-3 days). In F1 hybrid rats (Sprague Dawley x Fischer) males ingesting 100 microg OTA daily the steady state plasma value stabilised as in Fischer males, but females on the same diet accumulated OTA in plasma to nearly twice the value for males after only 5 months' exposure. Although OTA causes renal tumours in Fischer and Dark Agouti male rats in spite of marked difference in OTA elimination rates presently shown, understanding comparison of re-uptake along nephrons in rat and man in vivo is vital in applying rat toxicological data to assessment of risk of dietary OTA to humans.

  20. Composição e caracterização da fauna de mamíferos de médio e grande porte em uma pequena reserva de cerrado em Mato Grosso, Brasil Composition and characterization of the medium and large size mammal fauna in a small cerrado reserve in Mato Grosso, Brazil

    Directory of Open Access Journals (Sweden)

    Ednaldo Cândido Rocha

    2006-08-01

    Full Text Available Este estudo foi realizado na Reserva Biológica Municipal "Mário Viana", Nova Xavantina, MT, objetivando inventariar e avaliar a abundância e diversidade de mamíferos terrestres de médio e grande porte. Para tanto, foram realizadas duas visitas mensais a um transecto com 2.820 m de extensão, durante todo o ano de 2001, para o levantamento de pegadas (rastreamentos e outras evidências de mamíferos. Um total de 29 espécies foram registradas na área de estudo, sendo que 22 ocorreram no transecto e tiveram suas seqüências individuais de pegadas quantificadas para realização do cálculo dos índices de abundância e de diversidade de Shannon-Wiener (H'. De acordo com seus índices de abundância, as espécies foram classificadas em raras, comuns e abundantes. Dentre outras, onça-parda (Puma concolor - Linnaeus, 1771 e tatu-canastra (Priodontes maximus - Keer, 1792 mostraram-se raras; jaguatirica (Leopardus pardalis - Linnaeus, 1758, e tamanduá-bandeira (Myrmecophaga tridactyla - Linnaeus, 1758, comuns; e cutia (Dasyprocta azarae - Lichtenstein, 1823 e tapeti (Sylvilagus brasiliensis - Linnaeus, 1758, abundantes. O H' encontrado foi 2,40, sendo considerado significativo. O presente trabalho apontou que, apesar de pequena (470 ha, a área de estudo desempenha importante papel para a conservação da mastofauna da região de Nova Xavantina, MT.This study was carried out at the 'Mario Viana' Municipal Biological Reserve in Nova Xavantina, MT, aiming to make an inventory and evaluate the abundance and diversity of terrestrial mammals of medium and large size. Thus, two monthly visits were made to a 2.820 m long transect throughout 2001 to assess tracking and other evidences of mammals. Twenty-nine species were recorded in the study area, with 22 in the transect and two individual tracking sequences being quantified for calculation of the Shannon-Wiener (H' abundance and diversity indices. According to the abundance indices, the species were

  1. Environmentally associated ticks (Acari: Ixodidae in Campo Grande, Mato Grosso do Sul, Brazil Carrapatos (Acari: Ixodidae associados com o ambiente em Campo Grande, Mato Grosso do Sul, Brasil

    Directory of Open Access Journals (Sweden)

    Marcos Valério Garcia

    2013-03-01

    Full Text Available Herein, we report tick species found on wild and domestic animals and in the environment during a one-year sampling period at the Brazilian Farming Research Company beef cattle unit (Embrapa Beef Cattle, which is located within the urban area of Campo Grande, Mato Grosso do Sul, Brazil. From 55 wild hosts including six different species (Nasua nasua, Cebus spp., Cerdocyon thous, Myrmecophaga tridactyla, Tamandua tetradactyla and Dasyprocta aguti, 323 ticks were collected. Amblyomma ovale ticks were found solely on coatis, and Amblyomma nodosum was identified solely on anteaters. No ticks were found on capuchin monkeys. However, Amblyomma cajennense was found on all parasitized host species with the exception of capuchin monkeys. Giant anteaters displayed the highest infestation abundance, with a mean of 53 ticks∕animal. Environmental sampling yielded 166 adult A. cajennense ticks. The tick species found on domestic animals (Rhipicephalus (Boophilus microplus, R. sanguineus, Dermacentor nitens and A. cajennense were those typically found on these hosts in Brazil. The most prevalent tick species, A. cajennense, was found on both wild and domestic animals and was also prevalent in the environment. Thus, this tick species is the primary vector that allows pathogens to bridge wild and domestic animals in the Cerrado.Neste trabalho são descritas as espécies de carrapatos de animais selvagens e domésticos e do ambiente coletados por um ano na EMBRAPA Gado de Corte localizado na área urbana de Campo Grande, Mato Grosso do Sul, Brasil. Dos 55 hospedeiros selvagens de seis espécies diferentes (Nasua nasua, Cebus spp., Cerdocyon thous, Myrmecophaga tridactyla, Tamandua tetradactyla e Dasyprocta aguti foram coletados 323 carrapatos. Amblyomma ovale foi encontrado apenas em quatis e Amblyomma nodosum apenas sobre tamanduás. Nenhum carrapato foi encontrado sobre macacos-prego. Por outro lado, Amblyomma cajennense foi encontrado em todos os hospedeiros

  2. Composição e abundância relativa dos mamíferos de médio e grande porte no Parque Estadual do Turvo, Rio Grande do Sul, Brasil Composition and relative abundance of the medium-large ized mammals of Turvo State Park, Rio Grande do Sul, Brazil

    Directory of Open Access Journals (Sweden)

    Carlos B. Kasper

    2007-12-01

    Full Text Available Entre janeiro de 2005 e dezembro de 2006 foram realizados estudos sobre a composição e abundância relativa dos mamíferos de médio e grande porte do Parque Estadual do Turvo. Para tanto, foram utilizados registros de armadilhas fotográficas além de visualizações e dados sobre presença e ausência de pegadas ao longo de transectos pré-determinados. No total foram registradas 29 espécies de mamíferos de médio e grande porte, das quais Dasyprocta azarae Lichtenstein, 1823 e Sylvilagus brasiliensis (Linnaeus, 1758 foram as espécies com maior número de registros. No que se refere a Carnivora, Nasua nasua (Linnaeus, 1766 e Leopardus pardalis (Linnaeus, 1758 tiveram os maiores índices de registro, enquanto Leopardus tigrinus (Schreber, 1775, Leopardus wiedii (Schinz, 1782 e Galictis cuja (Molina 1782 os menores. Entre os ungulados apenas Pecari tajacu (Linnaeus, 1758 mostrou-se freqüente, sendo a quarta espécie em número de registros. Algumas espécies comuns em outros ambientes apresentaram baixos índices de registro no Parque Estadual do Turvo, tais como Dasypus novemcinctus Linnaeus, 1758 e Didelphis albiventris Lund, 1840. Finalmente, constata-se a provável extinção local de Tayassu pecari (Link, 1795, uma vez que não foram obtidos registros de sua presença ao longo do estudo. A conservação dos mamíferos de médio e grande porte do Parque está fortemente associada à preservação do "Corredor Verde de Misiones", que provavelmente representa uma área fonte para diversas espécies.Between January of 2005 and December of 2006, studies on the composition and relative abundance of medium and large sized mammals were carried out in Turvo State Park. Records came from camera-trapping, in addition to visualization and presence and absence data from track surveys along pre determined transects. At total, 29 species of medium-large sized mammals were listed. Of these, Dasyprocta azarae Lichtenstein, 1823 and Sylvilagus

  3. The hypothalamus and the regulation of energy homeostasis: lifting the lid on a black box.

    Science.gov (United States)

    Williams, G; Harrold, J A; Cutler, D J

    2000-08-01

    The hypothalamus is the focus of many peripheral signals and neural pathways that control energy homeostasis and body weight. Emphasis has moved away from anatomical concepts of 'feeding' and 'satiety' centres to the specific neurotransmitters that modulate feeding behaviour and energy expenditure. We have chosen three examples to illustrate the physiological roles of hypothalamic neurotransmitters and their potential as targets for the development of new drugs to treat obesity and other nutritional disorders. Neuropeptide Y (NPY) is expressed by neurones of the hypothalamic arcuate nucleus (ARC) that project to important appetite-regulating nuclei, including the paraventricular nucleus (PVN). NPY injected into the PVN is the most potent central appetite stimulant known, and also inhibits thermogenesis; repeated administration rapidly induces obesity. The ARC NPY neurones are stimulated by starvation, probably mediated by falls in circulating leptin and insulin (which both inhibit these neurones), and contribute to the increased hunger in this and other conditions of energy deficit. They therefore act homeostatically to correct negative energy balance. ARC NPY neurones also mediate hyperphagia and obesity in the ob/ob and db/db mice and fa/fa rat, in which leptin inhibition is lost through mutations affecting leptin or its receptor. Antagonists of the Y5 receptor (currently thought to be the NPY 'feeding' receptor) have anti-obesity effects. Melanocortin-4 receptors (MC4-R) are expressed in various hypothalamic regions, including the ventromedial nucleus and ARC. Activation of MC4-R by agonists such as alpha-melanocyte-stimulating hormone (a cleavage product of pro-opiomelanocortin which is expressed in ARC neurones) inhibits feeding and causes weight loss. Conversely, MC4-R antagonists such as 'agouti' protein and agouti gene-related peptide (AGRP) stimulate feeding and cause obesity. Ectopic expression of agouti in the hypothalamus leads to obesity in the AVY

  4. Observações sobre calazar em Jacobina, Bahia. VI - Investigações sobre reservatórios silvestres e comensais

    Directory of Open Access Journals (Sweden)

    I. A. Sherlock

    1988-03-01

    Full Text Available Durante os anos de 1982 a 1986, a investigação sobre mamíferos comensais e silvestres, da periferia da cidade de Jacobina, Bahia, mostrou, ao lado do escasso número de exemplares, uma reduzida variedade específica dessa fauna. Capturou-se apenas 11 espécies, entre as quais, predominou o Didelphis albiventris, que abrangeu 44% dos 213 espécimens capturados. Entre os 193 com exames já concluídos, 84 eram exemplares de D. albiventris e 2 estavam infectados pela Leishmania donovani senso lato, 1 por L. mexicana amazonensis, 1 por L. braziliensis, subespécie e 3 por Trypanosoma cruzi Também foram observadas formas suspeitas de serem amastigotas de leishmanics, nos esfregaços de órgãos de 3 exemplares de Dasyprocta aguti, 1 Cercomys cunicularius - e 1 Oryzomys eliurus. 0 restante dos exemplares, inclusive 14 de Lycalopex vetulus, estava negativo para flagelados. Apesar de reforçado por outros indicadores epidemiológicos, como a predominância específica, a freqüência domiciliar, a atratividade para a vetora Lutzomyia longipalpis, e a concomitância com casos humanos nos mesmos locais, o índice de 2,3% de infecção natural do Didelphis albiventris, não autoriza a conclusão definitiva de ser o marsupial o mais importante reservatório natural da leishmaniose visceral em Jacobina.

  5. Polyspecific associations between squirrel monkeys (Saimiri sciureus) and other primates in eastern Amazonia.

    Science.gov (United States)

    Pinheiro, Tatyana; Ferrari, Stephen F; Lopes, Maria Aparecida

    2011-11-01

    One of the most common types of polyspecific association observed in Neotropical primate communities is that between squirrel monkeys (Saimiri) and capuchins (Cebus). The present study focused on association patterns in two Saimiri sciureus groups in eastern Brazilian Amazonia, between March and October, 2009. The associations were analyzed in terms of the species involved, the degree of association, and niche breadth and overlap. The study involved two S. sciureus groups (B4 and GI) on the right and left bank of the Tocantins River, respectively, within the area of the Tucuruí reservoir in southeastern Pará. Relations between species were classified as associations (individuals within 50 m and moving in the same direction), and encounters (individuals within 50 m and no coordinated movement). Group B4 was in association with Cebus apella during 100% of monitoring, and with Chiropotes satanas in 20.2%. By contrast, Group GI associated with Cebus 54.8% of the time, and with Chiropotes utahickae 2.5%. Encounters with Alouatta belzebul and Saguinus niger were recorded at both sites, with Aotus azarae and Dasyprocta prymnolopha at B4, and with Callicebus moloch, Dasyproct aleporina, Mazama gouazoubira, and Nasua nasua at GI. Overall, Saimiri had a broader niche than Cebus in terms of vertical spacing and diet, but not for substrate use. This pattern did not appear to be affected by association. While group GI spent significantly (P < 0.05) more time in association with Cebus during the wet season, group B4 associated with Chiropotes more during the dry season. Despite the higher association rates, niche overlap was greater for all variables at B4. This may reflect differences in the ranging and foraging patterns at the two sites, and the varying potential benefits of association for Saimiri. © 2011 Wiley Periodicals, Inc.

  6. Frugivoría y dispersión de semillas de la palma Oenocarpus bataua (Arecaceae en un bosque de los Andes colombianos

    Directory of Open Access Journals (Sweden)

    Rosario Rojas-Robles

    2012-12-01

    Full Text Available En zonas bajas tropicales, en bosques continuos y relativamente poco intervenidos, los frutos de la palma Oenocarpus bataua Mart., son consumidos por diversas especies de vertebrados, sin embargo, no hay estudios de dispersión de más largo plazo con esta especie. Entre agosto 2005-septiembre 2006 se realizaron observaciones de remoción de frutos, conteo de frutos comidos, observaciones focales, registros de frugivoría mediante trampas fotográficas, experimentos de dispersión y parcelas para determinar distribución espacial de Oenocarpus bataua. Cinco especies de mamíferos comen, dispersan, entierran (Sciurus granatensis, Microsciurus mimulus, Dasyprocta punctata y Proechimys sp., tapan (Marmosa robinsoni y llevan a las cuevas (Marmosa robinsoni y Proechimys sp., los frutos de O. bataua, sin dañar la semilla. El 21.7% de los frutos fueron dispersados, 13.2% roídos o pelados, 5.6% tapados, enterrados y llevados a cuevas. La distancia media de remoción de semillas y frutos fue 3.1m, aunque en menor proporción se registraron eventos de dispersión > a 50m. La abundante producción, el tamaño, el peso, la intensa remoción de los frutos por frugívoros, las cortas distancias de dispersión, la ausencia de frugívoros de gran porte disminuidos por cacería y fragmentación, encargados de la dispersión de larga distancia y el aumento de roedores, especialmente ardillas que presionan fuertemente el recurso frutos, generan una lluvia de semillas espacialmente restringida, posiblemente responsable de los patrones de distribución agregados en semillas, plántulas y posteriormente en juveniles y sub-adultos.

  7. Role of Reactive Oxygen Species in Hypothalamic Regulation of Energy Metabolism

    Directory of Open Access Journals (Sweden)

    Sabrina Diano

    2013-03-01

    Full Text Available To understand the etiology of metabolic disorders, including obesity and type II diabetes, it is essential to gain better insight into how stored and available energy sources are monitored by the central nervous system. In particular, a comprehension of the fine cellular interplay and intracellular mechanisms that enable appropriate hypothalamic and consequent endocrine and behavioral responses to both circulating hormonal and nutrient signals remains elusive. Recent data, including those from our laboratories, raised the notion that reactive oxygen species (ROS generation is not merely a by-product of substrate oxidation, but it plays a crucial role in modulating cellular responses involved in the regulation of energy metabolism. These review summarizes the published recent data on the effect of ROS levels in the regulation of neuronal function, including that of hypothalamic melanocortin neurons, pro-opiomelanocortin and neuropeptide Y-/agouti related peptide-neurons, in the modulation of food intake.

  8. Evaluating the potential roles of the Gray and Extension loci in the coat coloration of Thoroughbred racing horses.

    Science.gov (United States)

    Sakamoto, Takahiro; Fawcett, Jeffrey A; Innan, Hideki

    2017-01-01

    Horses have substantial variation in coat color, and the genetic loci responsible for the coat color variations have been well investigated. It has been believed that some color variations should follow a single-locus Mendelian law. Examples include the Gray locus that causes the gray phenotype and the Extension locus that specifies the chestnut phenotype. We reevaluated the roles of the Gray and Extension loci by using a large number of mating records of Thoroughbred racing horses. We showed that the data indeed fits the Mendelian law extremely well for the two loci. Furthermore, we demonstrated that the Extension and Agouti loci might have an additional role in determining the degree of melanin that should distinguish bay, dark bay, and brown.

  9. Epigenomic Adaptation to Low Dose Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Gould, Michael N. [Univ. of Wisconsin, Madison, WI (United States)

    2015-06-30

    The overall hypothesis of this grant application is that the adaptive responses elicited by low dose ionizing radiation (LDIR) result in part from heritable DNA methylation changes in the epigenome. In the final budget period at the University of Wisconsin-Madison, we will specifically address this hypothesis by determining if the epigenetically labile, differentially methylated regions (DMRs) that regulate parental-specific expression of imprinted genes are deregulated in agouti mice by low dose radiation exposure during gestation. This information is particularly important to ascertain given the 1) increased human exposure to medical sources of radiation; 2) increased number of people predicted to live and work in space; and 3) enhanced citizen concern about radiation exposure from nuclear power plant accidents and terrorist ‘dirty bombs.’

  10. Food intake regulating-neuropeptides are expressed and regulated through pregnancy and following food restriction in rat placenta

    Directory of Open Access Journals (Sweden)

    Cepeda Libia A

    2008-04-01

    Full Text Available Abstract Background Neuropeptide Y (NPY, agouti related peptide (AgRP, cocaine and amphetamine-regulated transcript (CART and melanocortins, the products of the proopiomelanocortin (POMC, are hypothalamic peptides involved in feeding regulation and energy homeostasis. Recent evidence has demonstrated their expression in rat and human placenta. Methods In the current study, we have investigated the expression of those neuropeptides in the rat placenta by real-time PCR using a model of maternal food restriction. Results Our results showed that placental-derived neuropeptides were regulated through pregnancy and following food restriction. Conclusion These data could indicate that placental-derived neuropeptides represent a local regulatory circuit that may fine-tune control of energy balance during pregnancy.

  11. Pigment patterns in adult fish result from superimposition of two largely independent pigmentation mechanisms.

    Science.gov (United States)

    Ceinos, Rosa M; Guillot, Raúl; Kelsh, Robert N; Cerdá-Reverter, José M; Rotllant, Josep

    2015-03-01

    Dorso-ventral pigment pattern differences are the most widespread pigmentary adaptations in vertebrates. In mammals, this pattern is controlled by regulating melanin chemistry in melanocytes using a protein, agouti-signalling peptide (ASIP). In fish, studies of pigment patterning have focused on stripe formation, identifying a core striping mechanism dependent upon interactions between different pigment cell types. In contrast, mechanisms driving the dorso-ventral countershading pattern have been overlooked. Here, we demonstrate that, in fact, zebrafish utilize two distinct adult pigment patterning mechanisms - an ancient dorso-ventral patterning mechanism, and a more recent striping mechanism based on cell-cell interactions; remarkably, the dorso-ventral patterning mechanism also utilizes ASIP. These two mechanisms function largely independently, with resultant patterns superimposed to give the full pattern. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Emerging Signaling Pathway in Arcuate Feeding-Related Neurons: Role of the Acbd7

    Directory of Open Access Journals (Sweden)

    Damien Lanfray

    2017-06-01

    Full Text Available The understanding of the mechanisms whereby energy balance is regulated is essential to the unraveling of the pathophysiology of obesity. In the last three decades, focus was put on the metabolic role played by the hypothalamic neurons expressing proopiomelanocortin (POMC and cocaine and amphetamine regulated transcript (CART and the neurons co-localizing agouti-related peptide (AgRP, neuropeptide Y (NPY, and gamma-aminobutyric acid (GABA. These neurons are part of the leptin-melanocortin pathway, whose role is key in energy balance regulation. More recently, the metabolic involvement of further hypothalamic uncharacterized neuron populations has been suggested. In this review, we discuss the potential homeostatic implication of hypothalamic GABAergic neurons that produce Acyl-Coa-binding domain containing protein 7 (ACBD7, precursor of the nonadecaneuropeptide (NDN, which has recently been characterized as a potent anorexigenic neuropeptide capable of relaying the leptin anorectic/thermogenic effect via the melanocortin system.

  13. Increased insulin and leptin sensitivity in mice lacking acyl CoA:diacylglycerol acyltransferase 1.

    Science.gov (United States)

    Chen, Hubert C; Smith, Steven J; Ladha, Zuleika; Jensen, Dalan R; Ferreira, Luis D; Pulawa, Leslie K; McGuire, James G; Pitas, Robert E; Eckel, Robert H; Farese, Robert V

    2002-04-01

    Acyl coenzyme A:diacylglycerol acyltransferase 1 (DGAT1) is one of two known DGAT enzymes that catalyze the final step in mammalian triglyceride synthesis. DGAT1-deficient mice are resistant to diet-induced obesity through a mechanism involving increased energy expenditure. Here we show that these mice have decreased levels of tissue triglycerides, as well as increased sensitivity to insulin and to leptin. Importantly, DGAT1 deficiency protects against insulin resistance and obesity in agouti yellow mice, a model of severe leptin resistance. In contrast, DGAT1 deficiency did not affect energy and glucose metabolism in leptin-deficient (ob/ob) mice, possibly due in part to a compensatory upregulation of DGAT2 expression in the absence of leptin. Our results suggest that inhibition of DGAT1 may be useful in treating insulin resistance and leptin resistance in human obesity.

  14. ANÁLISIS GENÉTICO DE LA POBLACIÓN DE GATOS DEL NORTE Y SUR DE CALI, COLOMBIA

    OpenAIRE

    Andrés F. PEÑA-CRUZ; Stephania SANDOVAL ARANGO; Angie PATIÑO MONTOYA; Mailyn BEDOYA; Alejandra RODRÍGUEZ ORTIZ; Juan ORJUELA VASQUEZ; Alejandra ORTEGA; Juan F. LÓPEZ; Edward MOLINA HENAO; Angélica GUZMÁN; Julian GIL; Heiber CÁRDENAS HENAO

    2015-01-01

    Los marcadores genéticos del pelaje y malformaciones óseas han permitido caracterizar el perfil genético de más de 400 poblaciones del gato doméstico alrededor del mundo. Hace 15 años se estableció dicho perfil en la ciudad de Cali (Colombia). En este estudio se determinó si el norte y sur de Cali se comportan como subpoblaciones y se comparó el perfil total con el estudio pasado. Se encontró una disminución de la frecuencia alélica de a ( no-agouti ) y d ( dilution ), pero un aumento en cinc...

  15. Effect of long-term culturing on the potential of mouse embryonic stem cells for in vitro and in vivo development

    Energy Technology Data Exchange (ETDEWEB)

    Mitalipov, Sh.M.; Mitalipova, M.M.; Ivanov, V.I.

    1994-11-01

    We performed comparative analysis of in vitro and in vivo pluripotency for two clones of ES-D3 cells subjected to different number of passages after the beginning of subcloning. Both clones of ES cells produced characteristically shaped colonies and embryoid bodies during culturing in suspension. High activity of alkaline phosphatase was demonstrated in ES cells by cytochemical staining. The proportion of aneuploid ES cells increased with the increase in the number of passages, as shown by karyotyping. Experiments on producing chimeric mice using ES cells have shown that clone D3W (passage 17) exceeds clone D3M (passage 42) both in terms of chimera proportion among the offspring and in terms of the extent of coat chimerism (proportion of agouti coat color (ES component) in the coat of chimeras). 26 refs., 4 figs., 3 tabs.

  16. Mammalian comparative sequence analysis of the Agrp locus.

    Directory of Open Access Journals (Sweden)

    Christopher B Kaelin

    2007-08-01

    Full Text Available Agouti-related protein encodes a neuropeptide that stimulates food intake. Agrp expression in the brain is restricted to neurons in the arcuate nucleus of the hypothalamus and is elevated by states of negative energy balance. The molecular mechanisms underlying Agrp regulation, however, remain poorly defined. Using a combination of transgenic and comparative sequence analysis, we have previously identified a 760 bp conserved region upstream of Agrp which contains STAT binding elements that participate in Agrp transcriptional regulation. In this study, we attempt to improve the specificity for detecting conserved elements in this region by comparing genomic sequences from 10 mammalian species. Our analysis reveals a symmetrical organization of conserved sequences upstream of Agrp, which cluster into two inverted repeat elements. Conserved sequences within these elements suggest a role for homeodomain proteins in the regulation of Agrp and provide additional targets for functional evaluation.

  17. Generation of neuropeptidergic hypothalamic neurons from human pluripotent stem cells

    Science.gov (United States)

    Merkle, Florian T.; Maroof, Asif; Wataya, Takafumi; Sasai, Yoshiki; Studer, Lorenz; Eggan, Kevin; Schier, Alexander F.

    2015-01-01

    Hypothalamic neurons orchestrate many essential physiological and behavioral processes via secreted neuropeptides, and are relevant to human diseases such as obesity, narcolepsy and infertility. We report the differentiation of human pluripotent stem cells into many of the major types of neuropeptidergic hypothalamic neurons, including those producing pro-opiolemelanocortin, agouti-related peptide, hypocretin/orexin, melanin-concentrating hormone, oxytocin, arginine vasopressin, corticotropin-releasing hormone (CRH) or thyrotropin-releasing hormone. Hypothalamic neurons can be generated using a ‘self-patterning’ strategy that yields a broad array of cell types, or via a more reproducible directed differentiation approach. Stem cell-derived human hypothalamic neurons share characteristic morphological properties and gene expression patterns with their counterparts in vivo, and are able to integrate into the mouse brain. These neurons could form the basis of cellular models, chemical screens or cellular therapies to study and treat common human diseases. PMID:25670790

  18. Hypothalamic KLF4 mediates leptin's effects on food intake via AgRP

    Science.gov (United States)

    Imbernon, Monica; Sanchez-Rebordelo, Estrella; Gallego, Rosalia; Gandara, Marina; Lear, Pamela; Lopez, Miguel; Dieguez, Carlos; Nogueiras, Ruben

    2014-01-01

    Krüppel-like factor 4 (KLF4) is a zinc-finger-type transcription factor expressed in a range of tissues that plays multiple functions. We report that hypothalamic KLF4 represents a new transcription factor specifically modulating agouti-related protein (AgRP) expression in vivo. Hypothalamic KLF4 colocalizes with AgRP neurons and is modulated by nutritional status and leptin. Over-expression of KLF4 in the hypothalamic arcuate nucleus (ARC) induces food intake and increases body weight through the specific stimulation of AgRP, as well as blunting leptin sensitivity in lean rats independent of forkhead box protein 01 (FoxO1). Down-regulation of KLF4 in the ARC inhibits fasting-induced food intake in both lean and diet-induced obese (DIO) rats. Silencing KLF4, however, does not, on its own, enhance peripheral leptin sensitivity in DIO rats. PMID:24944903

  19. Hypothalamic Integration of Metabolic, Endocrine, and Circadian Signals in Fish: Involvement in the Control of Food Intake

    Science.gov (United States)

    Delgado, María J.; Cerdá-Reverter, José M.; Soengas, José L.

    2017-01-01

    The regulation of food intake in fish is a complex process carried out through several different mechanisms in the central nervous system (CNS) with hypothalamus being the main regulatory center. As in mammals, a complex hypothalamic circuit including two populations of neurons: one co-expressing neuropeptide Y (NPY) and Agouti-related peptide (AgRP) and the second one population co-expressing pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) is involved in the integration of information relating to food intake control. The production and release of these peptides control food intake, and the production results from the integration of information of different nature such as levels of nutrients and hormones as well as circadian signals. The present review summarizes the knowledge and recent findings about the presence and functioning of these mechanisms in fish and their differences vs. the known mammalian model. PMID:28694769

  20. Technical note: a novel method for routine genotyping of horse coat color gene polymorphisms.

    Science.gov (United States)

    Royo, L J; Fernández, I; Azor, P J; Alvarez, I; Pérez-Pardal, L; Goyache, F

    2008-06-01

    The aim of this note is to describe a reliable, fast, and cost-effective real-time PCR method for routine genotyping of mutations responsible for most coat color variation in horses. The melanocortin-1 receptor, Agouti-signaling peptide, and membrane-associated transporter protein alleles were simultaneously determined using 2 PCR protocols. The assay described here is an alternative method for routine genotyping of a defined number of polymorphisms. Allelic variants are detected in real time and no post-PCR manipulations are required, therefore limiting costs and possible carryover contamination. Data can be copied to a Microsoft Excel spreadsheet for semiautomatic determination of the genotype using a macro freely available at http://www.igijon.com/personales/fgoyache/software_i.htm (last accessed February 26, 2007). The performance of the method is demonstrated on 156 Spanish Purebred horses.

  1. Hunger-promoting hypothalamic neurons modulate effector and regulatory T-cell responses.

    Science.gov (United States)

    Matarese, Giuseppe; Procaccini, Claudio; Menale, Ciro; Kim, Jae Geun; Kim, Jung Dae; Diano, Sabrina; Diano, Nadia; De Rosa, Veronica; Dietrich, Marcelo O; Horvath, Tamas L

    2013-04-09

    Whole-body energy metabolism is regulated by the hypothalamus and has an impact on diverse tissue functions. Here we show that selective knockdown of Sirtuin 1 Sirt1 in hypothalamic Agouti-related peptide-expressing neurons, which renders these cells less responsive to cues of low energy availability, significantly promotes CD4(+) T-cell activation by increasing production of T helper 1 and 17 proinflammatory cytokines via mediation of the sympathetic nervous system. These phenomena were associated with an impaired thymic generation of forkhead box P3 (FoxP3(+)) naturally occurring regulatory T cells and their reduced suppressive capacity in the periphery, which resulted in increased delayed-type hypersensitivity responses and autoimmune disease susceptibility in mice. These observations unmask a previously unsuspected role of hypothalamic feeding circuits in the regulation of adaptive immune response.

  2. Effects of "Bioactive" amino acids leucine, glutamate, arginine and tryptophan on feed intake and mRNA expression of relative neuropeptides in broiler chicks

    Directory of Open Access Journals (Sweden)

    Wang Songbo

    2012-08-01

    Full Text Available Abstract Feed intake control is vital to ensuring optimal nutrition and achieving full potential for growth and development in poultry. The aim of the present study was to investigate the effects of L-leucine, L-glutamate, L-tryptophan and L-arginine on feed intake and the mRNA expression levels of hypothalamic Neuropeptide involved in feed intake regulation in broiler chicks. Leucine, glutamate, tryptophan or arginine was intra-cerebroventricularly (ICV administrated to 4d-old broiler chicks respectively and the feed intake were recorded at various time points. Quantitative PCR was performed to determine the hypothalamic mRNA expression levels of Neuropeptide Y (NPY, agouti related protein (AgRP, pro-opiomelanocortin (POMC, melanocortin receptor 4 (MC4R and corticotrophin releasing factor (CRF. Our results showed that ICV administration of L-leucine (0.15 or 1.5  μmol significantly (P P 

  3. Impact of animal strain on gene expression in a rat model of acute cardiac rejection

    Directory of Open Access Journals (Sweden)

    Norsworthy Kelly J

    2009-06-01

    Full Text Available Abstract Background The expression levels of many genes show wide natural variation among strains or populations. This study investigated the potential for animal strain-related genotypic differences to confound gene expression profiles in acute cellular rejection (ACR. Using a rat heart transplant model and 2 different rat strains (Dark Agouti, and Brown Norway, microarrays were performed on native hearts, transplanted hearts, and peripheral blood mononuclear cells (PBMC. Results In heart tissue, strain alone affected the expression of only 33 probesets while rejection affected the expression of 1368 probesets (FDR 10% and FC ≥ 3. Only 13 genes were affected by both strain and rejection, which was Conclusion In ACR, genetic background has a large impact on the transcriptome of immune cells, but not heart tissue. Gene expression studies of ACR should avoid study designs that require cross strain comparisons between leukocytes.

  4. Intraventricular administration of Tenebrio molitor larvae extract regulates food intake and body weight in mice with high-fat diet-induced obesity.

    Science.gov (United States)

    Seo, Minchul; Kim, Jongwan; Moon, Seong-Su; Hwang, Jae-Sam; Kim, Mi-Ae

    2017-08-01

    We recently reported the in vitro and in vivo antiobesity effects of Tenebrio molitor larvae, a traditional food in many countries, but it remains unknown how the larvae affect appetite regulation in mice with diet-induced obesity. We hypothesized that the extract of T molitor larvae mediates appetite by regulating neuropeptide expression. We investigated T molitor larvae extract's (TME's) effects on anorexigenesis and endoplasmic reticulum (ER) stress-induced orexigenic neuropeptide expression in the hypothalami of obese mice. Intracerebroventricular TME administration suppressed feeding by down-regulating the expression of the orexigenic neuropeptides neuropeptide Y and agouti-related protein. T molitor larvae extract significantly reduced the expression of ER stress response genes. These results suggest that TME and its bioactive components are potential therapeutics for obesity and ER stress-driven disease states. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Surfactant protein d deficiency in mice is associated with hyperphagia, altered fat deposition, insulin resistance, and increased Basal endotoxemia

    DEFF Research Database (Denmark)

    Stidsen, Jacob V; Khorooshi, Reza; Rahbek, Martin K U

    2012-01-01

    Pulmonary surfactant protein D (SP-D) is a host defence lectin of the innate immune system that enhances clearance of pathogens and modulates inflammatory responses. Recently it has been found that systemic SP-D is associated with metabolic disturbances and that SP-D deficient mice are mildly obese....... However, the mechanism behind SP-D's role in energy metabolism is not known.Here we report that SP-D deficient mice had significantly higher ad libitum energy intake compared to wild-type mice and unchanged energy expenditure. This resulted in accumulation but also redistribution of fat tissue. Blood...... pressure was unchanged. The change in energy intake was unrelated to the basal levels of hypothalamic Pro-opiomelanocortin (POMC) and Agouti-related peptide (AgRP) gene expression. Neither short time systemic, nor intracereberoventricular SP-D treatment altered the hypothalamic signalling or body weight...

  6. The central melanocortin system and the integration of short- and long-term regulators of energy homeostasis.

    Science.gov (United States)

    Ellacott, Kate L J; Cone, Roger D

    2004-01-01

    The importance of the central melanocortin system in the regulation of energy balance is highlighted by studies in transgenic animals and humans with defects in this system. Mice that are engineered to be deficient for the melanocortin-4 receptor (MC4R) or pro-opiomelanocortin (POMC) and those that overexpress agouti or agouti-related protein (AgRP) all have a characteristic obese phenotype typified by hyperphagia, increased linear growth, and metabolic defects. Similar attributes are seen in humans with haploinsufficiency of the MC4R. The central melanocortin system modulates energy homeostasis through the actions of the agonist, alpha-melanocyte-stimulating hormone (alpha-MSH), a POMC cleavage product, and the endogenous antagonist AgRP on the MC3R and MC4R. POMC is expressed at only two locations in the brain: the arcuate nucleus of the hypothalamus (ARC) and the nucleus of the tractus solitarius (NTS) of the brainstem. This chapter will discuss these two populations of POMC neurons and their contribution to energy homeostasis. We will examine the involvement of the central melanocortin system in the incorporation of information from the adipostatic hormone leptin and acute hunger and satiety factors such as peptide YY (PYY(3-36)) and ghrelin via a neuronal network involving POMC/cocaine and amphetamine-related transcript (CART) and neuropeptide Y (NPY)/AgRP neurons. We will discuss evidence for the existence of a similar network of neurons in the NTS and propose a model by which this information from the ARC and NTS centers may be integrated directly or via adipostatic centers such as the paraventricular nucleus of the hypothalamus (PVH).

  7. Delayed and short course of rapamycin prevents organ rejection after allogeneic liver transplantation in rats.

    Science.gov (United States)

    Hamdani, Salim; Thiolat, Allan; Naserian, Sina; Grondin, Cynthia; Moutereau, Stéphane; Hulin, Anne; Calderaro, Julien; Grimbert, Philippe; Cohen, José Laurent; Azoulay, Daniel; Pilon, Caroline

    2017-10-14

    To test whether a delayed and short course of rapamycin would induce immunosuppressive effects following allogeneic orthotopic liver transplantation (OLT) in rats. Allogeneic OLTs were performed using Dark Agouti livers transplanted into Lewis recipients, and syngeneic OLTs were performed using the Lewis rat strain. Rapamycin (1 mg/kg per day) was administered by gavage from day 4 to day 11 post-transplantation. Lymphocyte cellular compartments were analyzed by flow cytometry in draining lymph nodes, non-draining lymph nodes and the spleen at days 11 and 42 in rapamycin-treated rats, untreated control rats and syngeneic grafted rats. Skin grafts from Dark agouti or from F344 RT were performed at day 30 on liver grafted rats treated with rapamycin. An 8-d course of rapamycin treatment initiated 4 d following transplantation resulted in the survival of grafted rats for more than 100 d. In contrast, untreated rats died of liver failure within 13 to 21 d. The analysis of the cellular compartment revealed an increase in two cellular subpopulations, specifically myeloid-derived suppressor cells (MDSCs) and CD8+CD45RClow T cells, without major modifications in the regulatory T cell (Treg) compartment in treated rats in the early stages after grafting. We evaluated the ability of treated rats to reject third-party allogeneic skin grafts to confirm their immune competence. In contrast, when skin was collected from rats syngeneic to the grafted liver, it was not rejected. Our results demonstrate that short and delayed rapamycin treatment allows for tolerance in allogeneic OLT. The results also allowed for the identification of the mechanisms of tolerance induced by rapamycin by identifying MDSCs and CD8+CD45RClow T cells as associated with the state of tolerance.

  8. Candidate Gene Analysis Suggests Untapped Genetic Complexity in Melanin-Based Pigmentation in Birds.

    Science.gov (United States)

    Bourgeois, Yann X C; Bertrand, Joris A M; Delahaie, Boris; Cornuault, Josselin; Duval, Thomas; Milá, Borja; Thébaud, Christophe

    2016-07-01

    Studies on melanin-based color variation in a context of natural selection have provided a wealth of information on the link between phenotypic and genetic variation. Here, we evaluated associations between melanic plumage patterns and genetic polymorphism in the Réunion grey white-eye (Zosterops borbonicus), a species in which mutations on MC1R do not seem to play any role in explaining melanic variation. This species exhibits 5 plumage color variants that can be grouped into 3 color forms which occupy discrete geographic regions in the lowlands of Réunion, and a fourth high-elevation form which comprises 2 color morphs (grey and brown) and represents a true color polymorphism. We conducted a comprehensive survey of sequence variation in 96 individuals at a series of 7 candidate genes other than MC1R that have been previously shown to influence melanin-based color patterns in vertebrates, including genes that have rarely been studied in a wild bird species before: POMC, Agouti, TYR, TYRP1, DCT, Corin, and SLC24A5 Of these 7 genes, 2 (Corin and TYRP1) displayed an interesting shift in allele frequencies between lowland and highland forms and a departure from mutation-drift equilibrium consistent with balancing selection in the polymorphic highland form only. Sequence variation at Agouti, a gene frequently involved in melanin-based pigmentation patterning, was not associated with color forms or morphs. Thus, we suggest that functionally important changes in loci other than those classically studied are involved in the color polymorphism exhibited by the Réunion grey white-eye and possibly many other nonmodel species. © The American Genetic Association. 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. The differential expression of MC1R regulators in dorsal and ventral quail plumages during embryogenesis: Implications for plumage pattern formation.

    Science.gov (United States)

    Gluckman, Thanh-Lan; Mundy, Nicholas I

    2017-01-01

    Melanin pigmentation patterns are ubiquitous in animals and function in crypsis, physical protection, thermoregulation and signalling. In vertebrates, pigmentation patterns formed over large body regions as well as within appendages (hair/feathers) may be due to the differential distribution of pigment producing cells (melanocytes) and/or regulation of the melanin synthesis pathway. We took advantage of the pigmentation patterns of Japanese quail embryos (pale ventrum and patterned feathers dorsally) to explore the role of genes and their transcripts in regulating the function of the melanocortin-1-receptor (MC1R) via 1. activation: pro-opiomelanocortin (POMC), endoproteases prohormone convertase 1 (PC1) and 2 (PC2), and 2. inhibition-agouti signaling and agouti-related protein (ASIP and AGRP, respectively). Melanocytes are present in all feather follicles at both 8 and 12 days post-fertilisation (E8/E12), so differential deposition of melanocytes is not responsible for pigmentation patterns in embryonic quail. POMC transcripts expressed were a subset of those found in chicken and POMC expression within feather follicles was strong. PC1 was not expressed in feather follicles. PC2 was strongly expressed in all feather follicles at E12. ASIP transcript expression was variable and we report four novel ASIP transcripts. ASIP is strongly expressed in ventral feather follicles, but not dorsally. AGRP expression within feather follicles was weak. These results demonstrate that the pale-bellied quail phenotype probably involves inhibition of MC1R, as found previously. However, quail may require MC1R activation for eumelanogenesis in dorsal feathers which may have important implications for an understanding of colour pattern formation in vertebrates.

  10. Hypothalamic Non-AgRP, Non-POMC GABAergic Neurons Are Required for Postweaning Feeding and NPY Hyperphagia.

    Science.gov (United States)

    Kim, Eun Ran; Wu, Zhaofei; Sun, Hao; Xu, Yuanzhong; Mangieri, Leandra R; Xu, Yong; Tong, Qingchun

    2015-07-22

    The hypothalamus is critical for feeding and body weight regulation. Prevailing studies focus on hypothalamic neurons that are defined by selectively expressing transcription factors or neuropeptides including those expressing proopiomelanocortin (POMC) and agouti-related peptides (AgRP). The Cre expression driven by the pancreas-duodenum homeobox 1 promoter is abundant in several hypothalamic nuclei but not in AgRP or POMC neurons. Using this line, we generated mice with disruption of GABA release from a major subset of non-POMC, non-AgRP GABAergic neurons in the hypothalamus. These mice exhibited a reduction in postweaning feeding and growth, and disrupted hyperphagic responses to NPY. Disruption of GABA release severely diminished GABAergic input to the paraventricular hypothalamic nucleus (PVH). Furthermore, disruption of GABA-A receptor function in the PVH also reduced postweaning feeding and blunted NPY-induced hyperphagia. Given the limited knowledge on postweaning feeding, our results are significant in identifying GABA release from a major subset of less appreciated hypothalamic neurons as a key mediator for postweaning feeding and NPY hyperphagia, and the PVH as one major downstream site that contributes significantly to the GABA action. Significance statement: Prevalent studies on feeding in the hypothalamus focus on well characterized, selective groups neurons [e.g., proopiomelanocortin (POMC) and agouti-related peptide (AgRP) neurons], and as a result, the role of the majority of other hypothalamic neurons is largely neglected. Here, we demonstrated an important role for GABAergic projections from non-POMC non-AgRP neurons to the paraventricular hypothalamic nucleus in promoting postweaning (mainly nocturnal) feeding and mediating NPY-induced hyperphagia. Thus, these results signify an importance to study those yet to be defined hypothalamic neurons in the regulation of energy balance and reveal a neural basis for postweaning (nocturnal) feeding and

  11. Maternal ethanol consumption alters the epigenotype and the phenotype of offspring in a mouse model.

    Directory of Open Access Journals (Sweden)

    Nina Kaminen-Ahola

    2010-01-01

    Full Text Available Recent studies have shown that exposure to some nutritional supplements and chemicals in utero can affect the epigenome of the developing mouse embryo, resulting in adult disease. Our hypothesis is that epigenetics is also involved in the gestational programming of adult phenotype by alcohol. We have developed a model of gestational ethanol exposure in the mouse based on maternal ad libitum ingestion of 10% (v/v ethanol between gestational days 0.5-8.5 and observed changes in the expression of an epigenetically-sensitive allele, Agouti viable yellow (A(vy, in the offspring. We found that exposure to ethanol increases the probability of transcriptional silencing at this locus, resulting in more mice with an agouti-colored coat. As expected, transcriptional silencing correlated with hypermethylation at A(vy. This demonstrates, for the first time, that ethanol can affect adult phenotype by altering the epigenotype of the early embryo. Interestingly, we also detected postnatal growth restriction and craniofacial dysmorphology reminiscent of fetal alcohol syndrome, in congenic a/a siblings of the A(vy mice. These findings suggest that moderate ethanol exposure in utero is capable of inducing changes in the expression of genes other than A(vy, a conclusion supported by our genome-wide analysis of gene expression in these mice. In addition, offspring of female mice given free access to 10% (v/v ethanol for four days per week for ten weeks prior to conception also showed increased transcriptional silencing of the A(vy allele. Our work raises the possibility of a role for epigenetics in the etiology of fetal alcohol spectrum disorders, and it provides a mouse model that will be a useful resource in the continued efforts to understand the consequences of gestational alcohol exposure at the molecular level.

  12. The differential expression of MC1R regulators in dorsal and ventral quail plumages during embryogenesis: Implications for plumage pattern formation.

    Directory of Open Access Journals (Sweden)

    Thanh-Lan Gluckman

    Full Text Available Melanin pigmentation patterns are ubiquitous in animals and function in crypsis, physical protection, thermoregulation and signalling. In vertebrates, pigmentation patterns formed over large body regions as well as within appendages (hair/feathers may be due to the differential distribution of pigment producing cells (melanocytes and/or regulation of the melanin synthesis pathway. We took advantage of the pigmentation patterns of Japanese quail embryos (pale ventrum and patterned feathers dorsally to explore the role of genes and their transcripts in regulating the function of the melanocortin-1-receptor (MC1R via 1. activation: pro-opiomelanocortin (POMC, endoproteases prohormone convertase 1 (PC1 and 2 (PC2, and 2. inhibition-agouti signaling and agouti-related protein (ASIP and AGRP, respectively. Melanocytes are present in all feather follicles at both 8 and 12 days post-fertilisation (E8/E12, so differential deposition of melanocytes is not responsible for pigmentation patterns in embryonic quail. POMC transcripts expressed were a subset of those found in chicken and POMC expression within feather follicles was strong. PC1 was not expressed in feather follicles. PC2 was strongly expressed in all feather follicles at E12. ASIP transcript expression was variable and we report four novel ASIP transcripts. ASIP is strongly expressed in ventral feather follicles, but not dorsally. AGRP expression within feather follicles was weak. These results demonstrate that the pale-bellied quail phenotype probably involves inhibition of MC1R, as found previously. However, quail may require MC1R activation for eumelanogenesis in dorsal feathers which may have important implications for an understanding of colour pattern formation in vertebrates.

  13. Anti-inflammatory activity of a lipid fraction (lyprinol) from the NZ green-lipped mussel.

    Science.gov (United States)

    Whitehouse, M W; Macrides, T A; Kalafatis, N; Betts, W H; Haynes, D R; Broadbent, J

    1997-01-01

    A lipid-rich extract, preparared by supercritical fluid extraction of fresh stabilized mussel powder (Lyprinol), showed significant anti-inflammatory (AI) activity given therapeutically and prophylactically po to Wistar and Dark Agouti rats developing either (a) adjuvant-induced polyarthritis or (b) collagen(II)-induced autoallergic arthritis, with ED(50)/=25 mg/kg or various therapeutic oils (flaxseed, evening primrose, fish)>/=1800 mg/kg given orally. Lyprinol showed little or no activity in acute irritation assays (carrageenan, kaolin, histamine) indicating it is not mimicking rapid-acting NSAIDs.Incorporating Lyprinol into arthritigenic adjuvants composed of heat-killed Mycobacterium. tuberculosis suspended in olive oil or squalane, effectively prevented arthritis development at a dose of 5 mg/rat. By contrast, 'dummy adjuvants' prepared with Mycobacterium tuberculosis and flaxseed, evening primrose or fish oils were still arthritigenic in Dark Agouti rats (doses of oil=90 mg/rat).Lyprinol subfractions inhibited leukotriene-B(4) biosynthesis by stimulated human polymorphonuclear leukocytes in vitro, and prostaglandin-E(2) production by activated human macrophages in vitro. Much of this AI activity was associated with polyunsaturated fatty acids and natural antoxidants (carotenoids, etc.).In contrast to NSAIDs, Lyprinol is non-gastrotoxic in disease-stressed rats at 300 mg/kg po and does not seem to affect platelet aggregation (human, rat). These data show Lyprinol to be a reproducible, relatively stable, source of bioactive lipids with much greater potency than plant/marine oils currently used as nutritional supplements to ameliorate signs of inflammation.

  14. Water availability not fruitfall modulates the dry season distribution of frugivorous terrestrial vertebrates in a lowland Amazon forest.

    Directory of Open Access Journals (Sweden)

    Omar Stalin Landázuri Paredes

    Full Text Available Terrestrial vertebrate frugivores constitute one of the major guilds in tropical forests. Previous studies show that the meso-scale distribution of this group is only weakly explained by variables such as altitude and tree basal area in lowland Amazon forests. For the first time we test whether seasonally limiting resources (water and fallen fruit affect the dry season distribution in 25 species of terrestrial vertebrates. To examine the effects of the spatial availability of fruit and water on terrestrial vertebrates we used a standardized, regularly spaced arrangement of camera-traps within 25km2 of lowland Amazon forest. Generalized linear models (GLMs were then used to examine the influence of four variables (altitude, distance to large rivers, distance to nearest water, and presence vs absence of fruits on the number of photos on five functional groups (all frugivores, small, medium, large and very large frugivores and on seven of the most abundant frugivore species (Cuniculus paca, Dasyprocta leporina, Mazama americana, Mazama nemorivaga, Myoprocta acouchy, Pecari tajacu and Psophia crepitans. A total of 279 independent photos of 25 species were obtained from 900 camera-trap days. For most species and three functional groups, the variation in the number of photos per camera was significantly but weakly explained by the GLMs (deviance explained ranging from 6.2 to 48.8%. Generally, we found that the presence of water availability was more important than the presence of fallen fruit for the groups and species studied. Medium frugivores, large-bodied frugivores, and two of the more abundant species (C. paca and P. crepitans were recorded more frequently closer to water bodies; while none of the functional groups nor the most abundant species showed any significant relationship with the presence of fallen fruit. Two functional groups and two of the seven most common frugivore species assessed in the GLMs showed significant results with species

  15. Efeito das atividades de ecoturismo sobre a riqueza e a abundância de espécies de mamíferos de médio e grande porte na região do Cristalino, Mato Grosso, Brasil Effect of ecotourism activities on richness and abundance of species of medium and large mammals in the Cristalino region, Mato Grosso, Brazil

    Directory of Open Access Journals (Sweden)

    Ednaldo Cândido Rocha

    2012-12-01

    Full Text Available Este estudo foi desenvolvido nas Reservas Particulares do Patrimônio Natural Cristalino (670 ha e Lote Cristalino (6.539 ha e no Parque Estadual Cristalino (184.900 ha. Essas unidades de conservação são contíguas e estão localizadas no extremo centro-norte do estado do Mato Grosso, em locais considerados prioritários para a conservação, em função da alta biodiversidade e endemismos, além da elevada pressão antrópica. Desta forma, este trabalho objetivou conhecer, avaliar e comparar a estrutura das populações de mamíferos de médio e grande porte, em termos de riqueza e abundância das espécies em ambientes sem turismo e com atividades de ecoturismo na região do Cristalino. Para tanto, no período compreendido entre maio de 2008 a fevereiro de 2010 foram amostrados ambientes com floresta primária, os quais apresentavam dois níveis de perturbação antrópica: sem turismo e com atividades de ecoturismo. Os dados foram coletados utilizando a amostragem de distâncias em transecções lineares, que totalizou 468,3 Km percorridos nos períodos diurno e noturno, e registro de pegadas em parcelas previamente preparadas (n = 660 parcelas vistoriadas, além de percursos fluviais no rio Cristalino e buscas aleatórias nos locais onde não ocorriam caminhos. Registros de 37 espécies de mamíferos foram obtidos, sendo 33 de médio e grande porte e quatro de pequeno porte. Não houve diferença estatisticamente significativa na riqueza de espécies dos ambientes sem turismo e com ecoturismo, sendo que a similaridade de espécies entre eles foi alta (88%. No entanto, três táxons apresentaram abundância inferior nos ambientes com turismo: Dasyprocta leporina (Linnaeus, 1766, Mazama spp. e Dasypus kappleri Krauss, 1862. Percebe-se, portanto, que o impacto negativo das atividades de ecoturismo desenvolvidas na área de estudo foi de pequena magnitude, em termos de riqueza e abundância de mamíferos de médio e grande porte. Assim

  16. Frugivoría y dispersión de semillas de la palma Oenocarpus bataua (Arecaceae en un bosque de los Andes colombianos Frugivory and seed dispersal Oenocarpus bataua palm (Arecaceae in a forest from the Colombian Andes

    Directory of Open Access Journals (Sweden)

    Rosario Rojas-Robles

    2012-12-01

    Full Text Available En zonas bajas tropicales, en bosques continuos y relativamente poco intervenidos, los frutos de la palma Oenocarpus bataua Mart., son consumidos por diversas especies de vertebrados, sin embargo, no hay estudios de dispersión de más largo plazo con esta especie. Entre agosto 2005-septiembre 2006 se realizaron observaciones de remoción de frutos, conteo de frutos comidos, observaciones focales, registros de frugivoría mediante trampas fotográficas, experimentos de dispersión y parcelas para determinar distribución espacial de Oenocarpus bataua. Cinco especies de mamíferos comen, dispersan, entierran (Sciurus granatensis, Microsciurus mimulus, Dasyprocta punctata y Proechimys sp., tapan (Marmosa robinsoni y llevan a las cuevas (Marmosa robinsoni y Proechimys sp., los frutos de O. bataua, sin dañar la semilla. El 21.7% de los frutos fueron dispersados, 13.2% roídos o pelados, 5.6% tapados, enterrados y llevados a cuevas. La distancia media de remoción de semillas y frutos fue 3.1m, aunque en menor proporción se registraron eventos de dispersión > a 50m. La abundante producción, el tamaño, el peso, la intensa remoción de los frutos por frugívoros, las cortas distancias de dispersión, la ausencia de frugívoros de gran porte disminuidos por cacería y fragmentación, encargados de la dispersión de larga distancia y el aumento de roedores, especialmente ardillas que presionan fuertemente el recurso frutos, generan una lluvia de semillas espacialmente restringida, posiblemente responsable de los patrones de distribución agregados en semillas, plántulas y posteriormente en juveniles y sub-adultos.Seed dispersal is a key process that determines the spatial structure and dynamics of populations of plants, establishes the potential area of recruitment and in this way, the basis for subsequent processes such as predation, germination, competition and growth. The purpose of this research was to identify the guild of frugivores of the

  17. Signature of balancing selection at the MC1R gene in Kunming dog populations.

    Directory of Open Access Journals (Sweden)

    Guo-dong Wang

    Full Text Available Coat color in dog breeds is an excellent character for revealing the power of artificial selection, as it is extremely diverse and likely the result of recent domestication. Coat color is generated by melanocytes, which synthesize pheomelanin (a red or yellow pigment or eumelanin (a black or brown pigment through the pigment type-switching pathway, and is regulated by three genes in dogs: MC1R (melanocortin receptor 1, CBD103 (β-defensin 103, and ASIP (agouti-signaling protein precursor. The genotypes of these three gene loci in dog breeds are associated with coat color pattern. Here, we resequenced these three gene loci in two Kunming dog populations and analyzed these sequences using population genetic approaches to identify evolutionary patterns that have occurred at these loci during the recent domestication and breeding of the Kunming dog. The analysis showed that MC1R undergoes balancing selection in both Kunming dog populations, and that the Fst value for MC1R indicates significant genetic differentiation across the two populations. In contrast, similar results were not observed for CBD103 or ASIP. These results suggest that high heterozygosity and allelic differences at the MC1R locus may explain both the mixed color coat, of yellow and black, and the difference in coat colors in both Kunming dog populations.

  18. Heparanase affects food intake and regulates energy balance in mice.

    Directory of Open Access Journals (Sweden)

    Linda Karlsson-Lindahl

    Full Text Available Mutation of the melanocortin-receptor 4 (MC4R is the most frequent cause of severe obesity in humans. Binding of agouti-related peptide (AgRP to MC4R involves the co-receptor syndecan-3, a heparan sulfate proteoglycan. The proteoglycan can be structurally modified by the enzyme heparanase. Here we tested the hypothesis that heparanase plays a role in food intake behaviour and energy balance regulation by analysing body weight, body composition and food intake in genetically modified mice that either lack or overexpress heparanase. We also assessed food intake and body weight following acute central intracerebroventricular administration of heparanase; such treatment reduced food intake in wildtype mice, an effect that was abolished in mice lacking MC4R. By contrast, heparanase knockout mice on a high-fat diet showed increased food intake and maturity-onset obesity, with up to a 40% increase in body fat. Mice overexpressing heparanase displayed essentially the opposite phenotypes, with a reduced fat mass. These results implicate heparanase in energy balance control via the central melanocortin system. Our data indicate that heparanase acts as a negative modulator of AgRP signaling at MC4R, through cleavage of heparan sulfate chains presumably linked to syndecan-3.

  19. Interleukin-7, a new cytokine targeting the mouse hypothalamic arcuate nucleus: role in body weight and food intake regulation.

    Directory of Open Access Journals (Sweden)

    Laurence Macia

    Full Text Available Body weight is controlled through peripheral (white adipose tissue and central (mainly hypothalamus mechanisms. We have recently obtained evidence that overexpression of interleukin (IL-7, a critical cytokine involved in lymphopoiesis, can protect against the development of diet-induced obesity in mice. Here we assessed whether IL-7 mediated its effects by modulating hypothalamic function. Acute subcutaneous injection of IL-7 prevented monosodium glutamate-induced obesity, this being correlated with partial protection against cell death in the hypothalamic arcuate nucleus (ARC. Moreover, we showed that IL-7 activated hypothalamic areas involved in regulation of feeding behavior, as indicated by induction of the activation marker c-Fos in neural cells located in the ventromedial part of the ARC and by inhibition of food intake after fasting. Both chains of the IL-7 receptor (IL-7Ralpha and gamma(c were expressed in the ARC and IL-7 injection induced STAT-3 phosphorylation in this area. Finally, we established that IL-7 modulated the expression of neuropeptides that tune food intake, with a stimulatory effect on the expression of pro-opiomelanocortin and an inhibitory effect on agouti-related peptide expression in accordance with IL-7 promoting anorectic effects. These results suggest that the immunomodulatory cytokine IL-7 plays an important and unappreciated role in hypothalamic body weight regulation.

  20. Acute Lesioning and Rapid Repair of Hypothalamic Neurons outside the Blood-Brain Barrier

    Directory of Open Access Journals (Sweden)

    Ernie Yulyaningsih

    2017-06-01

    Full Text Available Neurons expressing agouti-related protein (AgRP are essential for feeding. The majority of these neurons are located outside the blood-brain barrier (BBB, allowing them to directly sense circulating metabolic factors. Here, we show that, in adult mice, AgRP neurons outside the BBB (AgRPOBBB were rapidly ablated by peripheral administration of monosodium glutamate (MSG, whereas AgRP neurons inside the BBB and most proopiomelanocortin (POMC neurons were spared. MSG treatment induced proliferation of tanycytes, the putative hypothalamic neural progenitor cells, but the newly proliferated tanycytes did not become neurons. Intriguingly, AgRPOBBB neuronal number increased within a week after MSG treatment, and newly emerging AgRP neurons were derived from post-mitotic cells, including some from the Pomc-expressing cell lineage. Our study reveals that the lack of protection by the BBB renders AgRPOBBB vulnerable to lesioning by circulating toxins but that the rapid re-emergence of AgRPOBBB is part of a reparative process to maintain energy balance.

  1. Effect of 24 h Fasting on Gene Expression of AMPK, Appetite Regulation Peptides and Lipometabolism Related Factors in the Hypothalamus of Broiler Chicks

    Directory of Open Access Journals (Sweden)

    Liu Lei

    2012-09-01

    Full Text Available The 5’-adenosine monophosphate-activated protein kinase (AMPK is a key part of a kinase-signaling cascade that acts to maintain energy homeostasis. The objective of this experiment was to investigate the possible effects of fasting and refeeding on the gene expression of hypothalamic AMPK, some appetitive regulating peptides and lipid metabolism related enzymes. Seven-day-old male broiler (Arbor Acres chicks were allocated into three equal treatments: fed ad libitum (control; fasted for 24 h; fasted for 24 h and then refed for 24 h. Compared with the control, the hypothalamic gene expression of AMPKα2, AMPKβ1, AMPKβ2, AMPKγ1, Ste20-related adaptor protein β (STRADβ, mouse protein 25α (MO25α and agouti-related peptide (AgRP were increased after fasting for 24 h. No significant difference among treatments was observed in mRNA levels of AMPKα1, AMPKγ2, LKB1 and neuropeptide Y (NPY. However, the expression of MO25β, pro-opiomelanocortin (POMC, corticotropin-releasing hormone (CRH, ghrelin, fatty acid synthase (FAS, acetyl-CoA carboxylase α (ACCα, carnitine palmitoyltransferase 1 (CPT-1 and sterol regulatory element binding protein-1 (SREBP-1 were significantly decreased. The present results indicated that 24 h fasting altered gene expression of AMPK subunits, appetite regulation peptides and lipometabolism related factors in chick’s hypothalamus; the hypothalamic FAS signaling pathway might be involved in the AMPK regulated energy homeostasis and/or appetite regulation in poultry.

  2. The cytokine ciliary neurotrophic factor (CNTF) activates hypothalamic urocortin-expressing neurons both in vitro and in vivo.

    Science.gov (United States)

    Purser, Matthew J; Dalvi, Prasad S; Wang, Zi C; Belsham, Denise D

    2013-01-01

    Ciliary neurotrophic factor (CNTF) induces neurogenesis, reduces feeding, and induces weight loss. However, the central mechanisms by which CNTF acts are vague. We employed the mHypoE-20/2 line that endogenously expresses the CNTF receptor to examine the direct effects of CNTF on mRNA levels of urocortin-1, urocortin-2, agouti-related peptide, brain-derived neurotrophic factor, and neurotensin. We found that treatment of 10 ng/ml CNTF significantly increased only urocortin-1 mRNA by 1.84-fold at 48 h. We then performed intracerebroventricular injections of 0.5 mg/mL CNTF into mice, and examined its effects on urocortin-1 neurons post-exposure. Through double-label immunohistochemistry using specific antibodies against c-Fos and urocortin-1, we showed that central CNTF administration significantly activated urocortin-1 neurons in specific areas of the hypothalamus. Taken together, our studies point to a potential role for CNTF in regulating hypothalamic urocortin-1-expressing neurons to mediate its recognized effects on energy homeostasis, neuronal proliferaton/survival, and/or neurogenesis.

  3. The cytokine ciliary neurotrophic factor (CNTF activates hypothalamic urocortin-expressing neurons both in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Matthew J Purser

    Full Text Available Ciliary neurotrophic factor (CNTF induces neurogenesis, reduces feeding, and induces weight loss. However, the central mechanisms by which CNTF acts are vague. We employed the mHypoE-20/2 line that endogenously expresses the CNTF receptor to examine the direct effects of CNTF on mRNA levels of urocortin-1, urocortin-2, agouti-related peptide, brain-derived neurotrophic factor, and neurotensin. We found that treatment of 10 ng/ml CNTF significantly increased only urocortin-1 mRNA by 1.84-fold at 48 h. We then performed intracerebroventricular injections of 0.5 mg/mL CNTF into mice, and examined its effects on urocortin-1 neurons post-exposure. Through double-label immunohistochemistry using specific antibodies against c-Fos and urocortin-1, we showed that central CNTF administration significantly activated urocortin-1 neurons in specific areas of the hypothalamus. Taken together, our studies point to a potential role for CNTF in regulating hypothalamic urocortin-1-expressing neurons to mediate its recognized effects on energy homeostasis, neuronal proliferaton/survival, and/or neurogenesis.

  4. Site and strain-specific variation in gut microbiota profiles and metabolism in experimental mice.

    Directory of Open Access Journals (Sweden)

    Melissa K Friswell

    2010-01-01

    Full Text Available The gastrointestinal tract microbiota (GTM of mammals is a complex microbial consortium, the composition and activities of which influences mucosal development, immunity, nutrition and drug metabolism. It remains unclear whether the composition of the dominant GTM is conserved within animals of the same strain and whether stable GTMs are selected for by host-specific factors or dictated by environmental variables.The GTM composition of six highly inbred, genetically distinct strains of mouse (C3H, C57, GFEC, CD1, CBA nu/nu and SCID was profiled using eubacterial -specific PCR-DGGE and quantitative PCR of feces. Animals exhibited strain-specific fecal eubacterial profiles that were highly stable (c. >95% concordance over 26 months for C57. Analyses of mice that had been relocated before and after maturity indicated marked, reproducible changes in fecal consortia and that occurred only in young animals. Implantation of a female BDF1 mouse with genetically distinct (C57 and Agoutie embryos produced highly similar GTM profiles (c. 95% concordance between mother and offspring, regardless of offspring strain, which was also reflected in urinary metabolite profiles. Marked institution-specific GTM profiles were apparent in C3H mice raised in two different research institutions.Strain-specific data were suggestive of genetic determination of the composition and activities of intestinal symbiotic consortia. However, relocation studies and uterine implantation demonstrated the dominance of environmental influences on the GTM. This was manifested in large variations between isogenic adult mice reared in different research institutions.

  5. Effect of starvation on transcriptomes of brain and liver in adult female zebrafish (Danio rerio)

    Science.gov (United States)

    Drew, Robert E.; Rodnick, Kenneth J.; Settles, Matthew; Wacyk, Jurij; Churchill, Erin; Powell, Madison S.; Hardy, Ronald W.; Murdoch, Gordon K.; Hill, Rodney A.; Robison, Barrie D.

    2008-01-01

    We used microarray and quantitative real-time PCR (qRT-PCR) analyses in adult female zebrafish (Danio rerio) to identify metabolic pathways regulated by starvation in the liver and brain. The transcriptome of whole zebrafish brain showed little response to 21 days of starvation. Only agouti-related protein 1 (agrp1) significantly responded, with increased expression in brains of starved fish. In contrast, a 21-day period of starvation significantly downregulated 466 and upregulated 108 transcripts in the liver, indicating an overall decrease in metabolic activity, reduced lipid metabolism, protein biosynthesis, proteolysis, and cellular respiration, and increased gluconeogenesis. Starvation also regulated expression of many components of the unfolded protein response, the first such report in a species other than yeast (Saccharomyces cerevisiae) and mice (Mus musculus). The response of the zebrafish hepatic transcriptome to starvation was strikingly similar to that of rainbow trout (Oncorhynchus mykiss) and less similar to mouse, while the response of common carp (Cyprinus carpio) differed considerably from the other three species. PMID:18728227

  6. Melanocortin 4 receptor-mediated hyperphagia and activation of neuropeptide Y expression in the dorsomedial hypothalamus during lactation.

    Science.gov (United States)

    Chen, Peilin; Williams, Sarah M; Grove, Kevin L; Smith, M Susan

    2004-06-02

    In several hyperphagic models, including lactation, in which hypothalamic melanocortin signaling is reduced, a novel expression of NPY mRNA in the dorsomedial hypothalamus (DMH) has been observed, suggesting that melanocortin signaling and the induced NPY in the DMH may constitute unique neurocircuitry in mediating energy balance. Using lactating rats as a model, the present study first showed that in the DMH abundant alpha-MSH and agouti-related protein fibers are in close apposition to NPY-positive cells. However, no NPY and MC4R (a melanocortin receptor) double-labeled neurons were observed. These data suggested that melanocortin input may synapse on presynaptic terminals that then synapse on DMH NPY cells. To study the function of DMH MC4Rs in energy balance, an MC3/4R-selective agonist, melanotan II (MTII), was injected bilaterally into the DMH. MTII injection significantly suppressed feeding induced by 24 hr fasting or suckling-induced hyperphagia. Furthermore, MTII treatment greatly attenuated suckling-induced NPY expression in the DMH. MTII treatment also stimulated uncoupling protein 1 activity in the brown adipose tissue of suckling female rats, indicative of increased sympathetic outflow. In summary, the present study demonstrated that the melanocortin system in the DMH not only plays an important role in inducing NPY expression in the DMH of lactating rats but also in regulating energy homeostasis, at least in part, by modulating appetite and energy expenditure.

  7. The effect of metformin on food intake and its potential role in hypothalamic regulation in obese diabetic rats.

    Science.gov (United States)

    Lv, Wen-Shan; Wen, Jun-Ping; Li, Li; Sun, Rui-Xia; Wang, Jing; Xian, Yu-Xin; Cao, Cai-Xia; Wang, Yun-Long; Gao, Yan-Yan

    2012-03-20

    Metformin appears to be involved in altering energy expenditure and thermogenesis, and could affect hypothalamic feeding circuits. However, it is not clear whether metformin is able to cross the blood-brain barrier (BBB) to reach the hypothalamus and exert a direct effect on the central nervous system. Here we show the presence of metformin in cerebrospinal fluid (CSF) of diabetic rats administered orally with metformin which was confirmed by detecting the concentration of metformin with liquid chromatography-tandem mass spectrometry. Food intake of diabetic rats treated with metformin was reduced, and glucose homeostasis was gained. Expression of orexigenic peptides neuropeptide Y (NPY) and agouti-related protein (AgRP) decreased in the hypothalamus of metformin-treated diabetic rats, though anorexigenic peptides pro-opiomelanocortin (POMC) did not change significantly. The phosphorylation of signal transducer and activator of transcription 3 (STAT3) was increased but phosphorylated AMP-activated kinase (AMPK) was similar in the hypothalamus of metformin-treated diabetic rats. Our findings suggest that metformin may cross BBB and play a central mechanism on regulation of food intake in the hypothalamus. The anorexic effect of metformin may be mediated by inhibition of NPY and AgRP gene expression through the STAT3 signaling pathway. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

  8. Effect of immobilization stress on the appetite and stomach ghrelin expression in maternal mice.

    Science.gov (United States)

    Li, Bing; Xu, Yuemei; Pan, Danqing; Xiao, Qian; Gao, Qi; Chen, Xin; Peng, Xiuhua; Du, Yuling; Gao, Pengfei

    2015-01-01

    Maternal stress exerts long-lasting postnatal growth on offspring, which persist into adulthood. However, the effect of maternal stress on appetizing system has not been widely reported. In this study, we found that maternal immobilization stress (IS) during lactation resulted in low body weight and food intake. Immunohistochemistry showed an increase in stomach ghrelin protein expression. The central regulation of body weight and food intake occurs in the hypothalamus, which contains multiple neuronal systems that play important roles in the regulation of energy homeostasis. These systems including multiple neuropeptides involve in the ghrelin pathway of appetite regulation. Therefore, real time reverse transcription polymerase chain reaction (RT-PCR) was used to measure the change of mRNA expression of ghrelin pathway related hormones in order to explore the mechanisms involved in the appetite regulation. Expression levels of the hypothalamic 5-hydroxytryptamine 2c receptor (5-HT2cR) and 5-HT2bR, which are essential for the development and function of ghrelin and leptin, were decreased, as well as those of corticotrophin releasing factor (CRF) and pro-opiomelanocortin (POMC). While the expression of growth hormone secretagogue receptor (GHSR), neuropeptide-Y (NPY) and agouti-related protein (AgRP) showed an increase with significant difference. These results suggest that stress in a postpartum mother has persistent effects on the body weight of their offspring. Increased ghrelin and decreased leptin expression in the stomach may play a role in these effects.

  9. Central inhibitory effects on feeding induced by the adipo-myokine irisin.

    Science.gov (United States)

    Ferrante, Claudio; Orlando, Giustino; Recinella, Lucia; Leone, Sheila; Chiavaroli, Annalisa; Di Nisio, Chiara; Shohreh, Rugia; Manippa, Fabio; Ricciuti, Adriana; Vacca, Michele; Brunetti, Luigi

    2016-11-15

    Irisin, the soluble secreted form of fibronectin type III domain containing 5 (FNDC5)-cleaved product, is a recently identified adipo-myokine that has been indicated as a possible link between physical exercise and energetic homeostasis. The co-localization of irisin with neuropeptide Y in hypothalamic sections of paraventricular nucleus, which receives NPY/AgRP projections from the arcuate nucleus, suggests a possible role of irisin in the central regulation of energy balance. In this context, in the present work we studied the effects of intra-hypothalamic irisin (1μl, 50-200nmol/l) administration on feeding and orexigenic [agouti-related peptide (AgRP), neuropeptide Y (NPY) and orexin-A] and anorexigenic [cocaine and amphetamine-regulated transcript (CART) and proopiomelanocortin (POMC)] peptides in male Sprague-Dawley rats. Furthermore, we evaluated the effects of irisin on hypothalamic dopamine (DA), norepinephrine (NE) and serotonin (5-hydroxytryptamine, 5-HT) concentrations and plasma NE levels. Compared to vehicle, irisin injected rats showed decreased food intake, possibly mediated by stimulated CART and POMC and inhibited DA, NE and orexin-A, in the hypothalamus. We also found increased plasma NE levels, supporting a role for sympathetic nervous system stimulation in mediating increased oxygen consumption by irisin. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. The Role of MicroRNA in the Modulation of the Melanocortinergic System.

    Science.gov (United States)

    Derghal, Adel; Djelloul, Mehdi; Trouslard, Jérôme; Mounien, Lourdes

    2017-01-01

    The central control of energy balance involves a highly regulated neuronal network within the hypothalamus and the dorsal vagal complex. In these structures, pro-opiomelanocortin (POMC) neurons are known to reduce meal size and to increase energy expenditure. In addition, leptin, a peripheral signal that relays information regarding body fat content, modulates the activity of melanocortin pathway neurons including POMC-, Agouti-related peptide (AgRP)/Neuropeptide Y (NPY)-, melanocortin receptors (MC3R and MC4R)-expressing neurons. MicroRNAs (miRNAs) are short non-coding RNAs of 22-26 nucleotides that post-transcriptionally interfere with target gene expression by binding to their mRNAs. Evidence has demonstrated that miRNAs play important roles in the central regulation of energy balance. In this context, different studies identified miRNAs including miR-200 family, miR-103, or miR-488 that could target the genes of melanocortin pathway. More precisely, these different miRNAs can modulate energy homeostasis by affecting leptin transduction pathway in the POMC, or AgRP/NPY neurons. This article reviews the role of identified miRNAs in the modulation of melanocortin pathway in the context of energy homeostasis.

  11. Hormone and glucose signalling in POMC and AgRP neurons.

    Science.gov (United States)

    Belgardt, Bengt F; Okamura, Tomoo; Brüning, Jens C

    2009-11-15

    In the wake of the obesity pandemic, increased research efforts are under way to define how peripheral hormones and metabolites regulate energy homeostasis. The melanocortin system, comprising anorexigenic proopiomelanocortin (POMC) expressing neurons and orexigenic agouti-related protein (AgRP)/neuropeptide Y (NPY) coexpressing neurons in the arcuate nucleus of the hypothalamus are crucial for normal energy homeostasis both in rodents and humans. They are regulated by peripheral hormones such as leptin and insulin, as well as nutrients such as glucose, amino acids and fatty acids. Although much progress has been made, recent reports continue to underline how restricted our understanding of POMC and AgRP/NPY neuron regulation by these signals is. Importantly, ATP-dependent potassium (K(ATP)) channels are regulated both by ATP (from glucose metabolism) and by leptin and insulin, and directly control electrical excitability of both POMC and AgRP neurons. Thus, this review attempts to offer an integrative overview about how peripheral signals, particularly leptin, insulin and glucose, converge on a molecular level in POMC and AgRP neurons of the arcuate nucleus of the hypothalamus to control energy homeostasis.

  12. Central melanocortins and the regulation of weight during acute and chronic disease.

    Science.gov (United States)

    Marks, D L; Cone, R D

    2001-01-01

    Recent advances in our understanding of the regulation of body weight, appetite, and metabolic rate have highlighted the role of the adipose-derived hormone leptin and its receptor as fundamental modulators of these processes. Investigations of the neural targets for leptin action--as well as characterization of the agouti obesity syndrome--have, in turn, led to the discovery of fundamental neural pathways involved in the central regulation of energy homeostasis. In particular, the central melanocortin system has been shown to regulate appetite and metabolic rate in rodents; mutations in this system have been demonstrated to result in obesity in humans. Overall, the melanocortin system appears to function as a bidirectional rheostat in the regulation of energy intake and expenditure in rodents and potentially in humans. The first section of this chapter will focus on the development of our understanding of melanocortin physiology in the context of obesity. In particular, recent data regarding the interplay between melanocortin and neuropeptide Y (NPY) signaling at a cellular level will be discussed. The following section will discuss the hypothesis that melanocortin signaling plays a role in pathological weight loss and hypermetabolism observed in murine cachexia models. The potential role of this system in integrating a variety of anorexic and cachexic signals, as well as the potential for its pharmacological manipulation in the treatment of human cachexia, will be discussed.

  13. A central role for C1q/TNF-related protein 13 (CTRP13 in modulating food intake and body weight.

    Directory of Open Access Journals (Sweden)

    Mardi S Byerly

    Full Text Available C1q/TNF-related protein 13 (CTRP13, a hormone secreted by adipose tissue (adipokines, helps regulate glucose metabolism in peripheral tissues. We previously reported that CTRP13 expression is increased in obese and hyperphagic leptin-deficient mice, suggesting that it may modulate food intake and body weight. CTRP13 is also expressed in the brain, although its role in modulating whole-body energy balance remains unknown. Here, we show that CTRP13 is a novel anorexigenic factor in the mouse brain. Quantitative PCR demonstrated that food restriction downregulates Ctrp13 expression in mouse hypothalamus, while high-fat feeding upregulates expression. Central administration of recombinant CTRP13 suppressed food intake and reduced body weight in mice. Further, CTRP13 and the orexigenic neuropeptide agouti-related protein (AgRP reciprocally regulate each other's expression in the hypothalamus: central delivery of CTRP13 suppressed Agrp expression, while delivery of AgRP increased Ctrp13 expression. Food restriction alone reduced Ctrp13 and increased orexigenic neuropeptide gene (Npy and Agrp expression in the hypothalamus; in contrast, when food restriction was coupled to enhanced physical activity in an activity-based anorexia (ABA mouse model, hypothalamic expression of both Ctrp13 and Agrp were upregulated. Taken together, these results suggest that CTRP13 and AgRP form a hypothalamic feedback loop to modulate food intake and that this neural circuit may be disrupted in an anorexic-like condition.

  14. Suppressive effects of a quinoxaline-analogue (Rob 803) on pathogenic immune mechanisms in collagen-induced arthritis.

    Science.gov (United States)

    Westman, E; Thi Ngoc, D D; Klareskog, L; Harris, H Erlandsson

    2008-04-01

    The anti-arthritic effects of the synthetic compound 9-chloro-2,3 dimethyl-6-(N,N-dimetylamino-2-oxoethyl)-6H-indolo[2,3-b] quinoxaline (Rob 803) was evaluated by treating Dark Agouti rats with collagen-induced arthritis using three different protocols. Daily subcutaneous treatment with 40 mg/kg/day of Rob 803 from the day of immunization and 14 days forward suppressed arthritis severity significantly and delayed the onset of clinical arthritis. In contrast, similar treatment initiated when individual rats had developed clinical disease (at a score of 2 points) did not suppress disease. Oral treatment with 35 mg/kg/day of Rob 803 from the day of immunization and 21 days forward resulted in a trend towards disease suppression. In vitro analysis of rats treated subcutaneously with Rob 803 revealed an inhibition of T cell proliferation but no effect on the generation of an anti-CII immunoglobulin G response. Further in vitro analysis demonstrated that Rob 803 also inhibited the generation of nitric oxide in macrophages, although at higher concentrations than needed for inhibitory effects on T cell proliferation. Thus we report that early subcutaneous administration of the synthetic substance Rob 803 has anti-rheumatic effects that are probably mediated by affecting the proliferative capacity of lymph node T cells. Rob 803 should be considered as a new candidate substance for anti-rheumatic treatment.

  15. Goldfish Leptin-AI and Leptin-AII: Function and Central Mechanism in Feeding Control.

    Science.gov (United States)

    Yan, Ai-Fen; Chen, Ting; Chen, Shuang; Ren, Chun-Hua; Hu, Chao-Qun; Cai, Yi-Ming; Liu, Fang; Tang, Dong-Sheng

    2016-05-30

    In mammals, leptin is a peripheral satiety factor that inhibits feeding by regulating a variety of appetite-related hormones in the brain. However, most of the previous studies examining leptin in fish feeding were performed with mammalian leptins, which share very low sequence homologies with fish leptins. To elucidate the function and mechanism of endogenous fish leptins in feeding regulation, recombinant goldfish leptin-AI and leptin-AII were expressed in methylotrophic yeast and purified by immobilized metal ion affinity chromatography (IMAC). By intraperitoneal (IP) injection, both leptin-AI and leptin-AII were shown to inhibit the feeding behavior and to reduce the food consumption of goldfish in 2 h. In addition, co-treatment of leptin-AI or leptin-AII could block the feeding behavior and reduce the food consumption induced by neuropeptide Y (NPY) injection. High levels of leptin receptor (lepR) mRNA were detected in the hypothalamus, telencephalon, optic tectum and cerebellum of the goldfish brain. The appetite inhibitory effects of leptins were mediated by downregulating the mRNA levels of orexigenic NPY, agouti-related peptide (AgRP) and orexin and upregulating the mRNA levels of anorexigenic cocaine-amphetamine-regulated transcript (CART), cholecystokinin (CCK), melanin-concentrating hormone (MCH) and proopiomelanocortin (POMC) in different areas of the goldfish brain. Our study, as a whole, provides new insights into the functions and mechanisms of leptins in appetite control in a fish model.

  16. Hyper abundant mesopredators and bird extinction in an Atlantic forest island

    Directory of Open Access Journals (Sweden)

    Mauro Galetti

    2009-06-01

    Full Text Available Islands can serve as model systems for understanding how biological invasions affect native species. Here we examine the negative effects of mesopredator mammals on bird richness at Anchieta Island, an 826 ha offshore island in the coast of Brazil. Anchieta Island has the highest density of mammals of the entire Atlantic forest, especially nest predators such as marmosets and coatis, introduced more than 20 years ago. This indiscriminate introduction of mammals may have affected directly the bird community, nowadays represented by 100 species comprised mainly by water-crossing birds, being 73 forest-dwelling species. A small component of these remnant bird species nests in tree holes and on the forest floor, null model analysis suggest that birds within these two nest types are under-represented on Anchieta Island. All guilds were affected negatively, but "opportunist insectivorous/omnivorous". Experiments using artificial nests showed a predation of 73% of nests on the floor while only 26% on the mainland. Camera traps recorded predation by coatis, agoutis, and opossums. The restoration of the bird community on this island is highly constrained by the high density of hyper abundant nest predators.

  17. Genetic diversity detection of the domestic horse (Equus caballus by genes associated with coat color

    Directory of Open Access Journals (Sweden)

    Luz Correa A

    2015-09-01

    Full Text Available Objective. To assess the population structure and genetic diversity in populations of domestic horse (Equus caballus in the municipality Cienaga de Oro-Córdoba (Colombia. Materials and methods. Random sampling were conducted between August and October 2013, in adult animals on farms seven districts, which was carried out phenotypic characterization of each animal, based on autosomal markers encoding morphological Extension (E , Agouti (A, Cream (C, White (W, Gray (G, Tobiano (TO, Overo (O and Roan (RN. Population genetic parameters: allele frequency, genetic diversity, gene flow, Hardy-Weinberg equilibrium and genetic distance were calculated through the program POPGENE 1.31; the genetic structure was assessed using the program FSTAT v. 2.9.3.2. Results. 341 individuals were analyzed in the seven populations studied, where the Extension gene Was the MOST faq frequently as the Overo and Tobiano genes showed the lowest values. Insignificant values of genetic variability and population recorded a global level, likewise, low genetic differentiation among populations, accompanied by a high gene flow was obtained; an excess of heterozygotes at population and global level was observed; to this is added the presence of Hardy-Weinberg equilibrium in all populations relative to the markers studied and low genetic distance values were reported. Conclusions. The populations are highly genetically related, a situation that may result from the existing geographical proximity between them, favoring genetic exchange and the establishment of a metapopulation.

  18. Signature of balancing selection at the MC1R gene in Kunming dog populations.

    Science.gov (United States)

    Wang, Guo-dong; Cheng, Lu-guang; Fan, Ruo-xi; Irwin, David M; Tang, Shu-sheng; Peng, Jian-guo; Zhang, Ya-ping

    2013-01-01

    Coat color in dog breeds is an excellent character for revealing the power of artificial selection, as it is extremely diverse and likely the result of recent domestication. Coat color is generated by melanocytes, which synthesize pheomelanin (a red or yellow pigment) or eumelanin (a black or brown pigment) through the pigment type-switching pathway, and is regulated by three genes in dogs: MC1R (melanocortin receptor 1), CBD103 (β-defensin 103), and ASIP (agouti-signaling protein precursor). The genotypes of these three gene loci in dog breeds are associated with coat color pattern. Here, we resequenced these three gene loci in two Kunming dog populations and analyzed these sequences using population genetic approaches to identify evolutionary patterns that have occurred at these loci during the recent domestication and breeding of the Kunming dog. The analysis showed that MC1R undergoes balancing selection in both Kunming dog populations, and that the Fst value for MC1R indicates significant genetic differentiation across the two populations. In contrast, similar results were not observed for CBD103 or ASIP. These results suggest that high heterozygosity and allelic differences at the MC1R locus may explain both the mixed color coat, of yellow and black, and the difference in coat colors in both Kunming dog populations.

  19. Temporal Change in Fur Color in Museum Specimens of Mammals: Reddish-Brown Species Get Redder with Storage Time

    Directory of Open Access Journals (Sweden)

    Andrew K. Davis

    2013-01-01

    Full Text Available Museum collections have great value for zoological research, but despite careful preservation, over time specimens can show subtle changes in color. We examined the effect of storage time on fur color of two reddish-brown species, golden mice (Ochrotomys nuttalli and eastern chipmunk (Tamias striatus. Using image analysis, we obtained color data (hue, saturation, and density on 91 golden mice and 49 chipmunks from Georgia, USA. Analyses that considered body size, gender, and collection year showed significant effects of year on fur color of golden mice (hue and saturation and of agouti color of chipmunks. Older specimens tended to be redder in color than newer specimens, consistent with a prior study of red bats (Lasiurus borealis. Hair samples showed reddening of fine body hairs, but not in thicker guard hairs. There was no temporal change in black or white stripe color in chipmunks, indicating that this temporal effect would be limited to species with reddish-brown fur. This effect may be caused by breakdown of eumelanin pigments (which make dark colors over time, leaving a greater proportion of pheomelanin pigments (which make red colors. These results show that storage time needs to be considered in research projects where fur color is of importance.

  20. A high-throughput fluorescence-based assay system for appetite-regulating gene and drug screening.

    Directory of Open Access Journals (Sweden)

    Yasuhito Shimada

    Full Text Available The increasing number of people suffering from metabolic syndrome and obesity is becoming a serious problem not only in developed countries, but also in developing countries. However, there are few agents currently approved for the treatment of obesity. Those that are available are mainly appetite suppressants and gastrointestinal fat blockers. We have developed a simple and rapid method for the measurement of the feeding volume of Danio rerio (zebrafish. This assay can be used to screen appetite suppressants and enhancers. In this study, zebrafish were fed viable paramecia that were fluorescently-labeled, and feeding volume was measured using a 96-well microplate reader. Gene expression analysis of brain-derived neurotrophic factor (bdnf, knockdown of appetite-regulating genes (neuropeptide Y, preproinsulin, melanocortin 4 receptor, agouti related protein, and cannabinoid receptor 1, and the administration of clinical appetite suppressants (fluoxetine, sibutramine, mazindol, phentermine, and rimonabant revealed the similarity among mechanisms regulating appetite in zebrafish and mammals. In combination with behavioral analysis, we were able to evaluate adverse effects on locomotor activities from gene knockdown and chemical treatments. In conclusion, we have developed an assay that uses zebrafish, which can be applied to high-throughput screening and target gene discovery for appetite suppressants and enhancers.

  1. Neuropeptide co-expression in hypothalamic kisspeptin neurons of laboratory animals and the human

    Directory of Open Access Journals (Sweden)

    Katalin eSkrapits

    2015-02-01

    Full Text Available Hypothalamic peptidergic neurons using kisspeptin (KP and its co-transmitters for communication are critically involved in the regulation of mammalian reproduction and puberty. This article provides an overview of neuropeptides present in KP neurons, with a focus on the human species. Immunohistochemical studies reveal that large subsets of human KP neurons synthesize neurokinin B, as also shown in laboratory species. In contrast, dynorphin described in KP neurons of rodents and sheep is found rarely in KP cells of human males and postmenopausal females. Similarly, galanin is detectable in mouse, but not human, KP cells, whereas substance P, cocaine- and amphetamine-regulated transcript and proenkephalin-derived opioids are expressed in varying subsets of KP neurons in humans, but not reported in ARC of other species. Human KP neurons do not contain neurotensin, cholecystokinin, proopiomelanocortin-derivatives, agouti-related protein, neuropeptide Y, somatostatin or tyrosine hydroxylase (dopamine. These data identify the possible co-transmitters of human KP cells. Neurochemical properties distinct from those of laboratory species indicate that humans use considerably different neurotransmitter mechanisms to regulate fertility.

  2. Exogenous schwann cells migrate, remyelinate and promote clinical recovery in experimental auto-immune encephalomyelitis.

    Directory of Open Access Journals (Sweden)

    Violetta Zujovic

    Full Text Available Schwann cell (SC transplantation is currently being discussed as a strategy that may promote functional recovery in patients with multiple sclerosis (MS and other inflammatory demyelinating diseases of the central nervous system (CNS. However this assumes they will not only survive but also remyelinate demyelinated axons in the chronically inflamed CNS. To address this question we investigated the fate of transplanted SCs in myelin oligodendrocyte glycoprotein (MOG-induced experimental autoimmune encephalomyelitis (EAE in the Dark Agouti rat; an animal model that reproduces the complex inflammatory demyelinating immunopathology of MS. We now report that SCs expressing green fluorescent protein (GFP-SCs allografted after disease onset not only survive but also migrate to remyelinate lesions in the inflamed CNS. GFP-SCs were detected more frequently in the parenchyma after direct injection into the spinal cord, than via intra-thecal delivery into the cerebrospinal fluid. In both cases the transplanted cells intermingled with astrocytes in demyelinated lesions, aligned with axons and by twenty one days post transplantation had formed Pzero protein immunoreactive internodes. Strikingly, GFP-SCs transplantation was associated with marked decrease in clinical disease severity in terms of mortality; all GFP-SCs transplanted animals survived whilst 80% of controls died within 40 days of disease.

  3. Exogenous Schwann Cells Migrate, Remyelinate and Promote Clinical Recovery in Experimental Auto-Immune Encephalomyelitis

    Science.gov (United States)

    Zujovic, Violetta; Doucerain, Cédric; Hidalgo, Antoine; Bachelin, Corinne; Lachapelle, François; Weissert, Robert; Stadelmann, Christine; Linington, Chris; Evercooren, Anne Baron-Van

    2012-01-01

    Schwann cell (SC) transplantation is currently being discussed as a strategy that may promote functional recovery in patients with multiple sclerosis (MS) and other inflammatory demyelinating diseases of the central nervous system (CNS). However this assumes they will not only survive but also remyelinate demyelinated axons in the chronically inflamed CNS. To address this question we investigated the fate of transplanted SCs in myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) in the Dark Agouti rat; an animal model that reproduces the complex inflammatory demyelinating immunopathology of MS. We now report that SCs expressing green fluorescent protein (GFP-SCs) allografted after disease onset not only survive but also migrate to remyelinate lesions in the inflamed CNS. GFP-SCs were detected more frequently in the parenchyma after direct injection into the spinal cord, than via intra-thecal delivery into the cerebrospinal fluid. In both cases the transplanted cells intermingled with astrocytes in demyelinated lesions, aligned with axons and by twenty one days post transplantation had formed Pzero protein immunoreactive internodes. Strikingly, GFP-SCs transplantation was associated with marked decrease in clinical disease severity in terms of mortality; all GFP-SCs transplanted animals survived whilst 80% of controls died within 40 days of disease. PMID:22984406

  4. Hunger-Driven Motivational State Competition.

    Science.gov (United States)

    Burnett, C Joseph; Li, Chia; Webber, Emily; Tsaousidou, Eva; Xue, Stephen Y; Brüning, Jens C; Krashes, Michael J

    2016-10-05

    Behavioral choice is ubiquitous in the animal kingdom and is central to goal-oriented behavior. Hypothalamic Agouti-related peptide (AgRP) neurons are critical regulators of appetite. Hungry animals, bombarded by multiple sensory stimuli, are known to modify their behavior during times of caloric need, rapidly adapting to a consistently changing environment. Utilizing ARC(AgRP) neurons as an entry point, we analyzed the hierarchical position of hunger related to rival drive states. Employing a battery of behavioral assays, we found that hunger significantly increases its capacity to suppress competing motivational systems, such as thirst, anxiety-related behavior, innate fear, and social interactions, often only when food is accessible. Furthermore, real-time monitoring of ARC(AgRP) activity revealed time-locked responses to conspecific investigation in addition to food presentation, further establishing that, even at the level of ARC(AgRP) neurons, choices are remarkably flexible computations, integrating internal state, external factors, and anticipated yield. VIDEO ABSTRACT. Published by Elsevier Inc.

  5. Understanding how discrete populations of hypothalamic neurons orchestrate complicated behavioral states

    Directory of Open Access Journals (Sweden)

    Allison eGraebner

    2015-08-01

    Full Text Available A major question in systems neuroscience is how a single population of neurons can interact with the rest of the brain to orchestrate complex behavioral states. The hypothalamus contains many such discrete neuronal populations that individually regulate arousal, feeding, and drinking. For example, hypothalamic neurons that express hypocretin (Hcrt neuropeptides can sense homeostatic and metabolic factors affecting wakefulness and orchestrate organismal arousal. Neurons that express agouti-related protein (AgRP can sense the metabolic needs of the body and orchestrate a state of hunger. The organum vasculosum of the lamina terminalis (OVLT can detect the hypertonicity of blood and orchestrate a state of thirst. Each hypothalamic population is sufficient to generate complicated behavioral states through the combined efforts of distinct efferent projections. The principal challenge to understanding these brain systems is therefore to determine the individual roles of each downstream projection for each behavioral state. In recent years, the development and application of temporally precise, genetically encoded tools have greatly improved our understanding of the structure and function of these neural systems. This review will survey recent advances in our understanding of how these individual hypothalamic populations can orchestrate complicated behavioral states due to the combined efforts of individual downstream projections.

  6. An excitatory paraventricular nucleus to AgRP neuron circuit that drives hunger.

    Science.gov (United States)

    Krashes, Michael J; Shah, Bhavik P; Madara, Joseph C; Olson, David P; Strochlic, David E; Garfield, Alastair S; Vong, Linh; Pei, Hongjuan; Watabe-Uchida, Mitsuko; Uchida, Naoshige; Liberles, Stephen D; Lowell, Bradford B

    2014-03-13

    Hunger is a hard-wired motivational state essential for survival. Agouti-related peptide (AgRP)-expressing neurons in the arcuate nucleus (ARC) at the base of the hypothalamus are crucial to the control of hunger. They are activated by caloric deficiency and, when naturally or artificially stimulated, they potently induce intense hunger and subsequent food intake. Consistent with their obligatory role in regulating appetite, genetic ablation or chemogenetic inhibition of AgRP neurons decreases feeding. Excitatory input to AgRP neurons is important in caloric-deficiency-induced activation, and is notable for its remarkable degree of caloric-state-dependent synaptic plasticity. Despite the important role of excitatory input, its source(s) has been unknown. Here, through the use of Cre-recombinase-enabled, cell-specific neuron mapping techniques in mice, we have discovered strong excitatory drive that, unexpectedly, emanates from the hypothalamic paraventricular nucleus, specifically from subsets of neurons expressing thyrotropin-releasing hormone (TRH) and pituitary adenylate cyclase-activating polypeptide (PACAP, also known as ADCYAP1). Chemogenetic stimulation of these afferent neurons in sated mice markedly activates AgRP neurons and induces intense feeding. Conversely, acute inhibition in mice with caloric-deficiency-induced hunger decreases feeding. Discovery of these afferent neurons capable of triggering hunger advances understanding of how this intense motivational state is regulated.

  7. Dietary macronutrient composition affects hypothalamic appetite regulation in chicks.

    Science.gov (United States)

    McConn, Betty R; Matias, Justin; Wang, Guoqing; Cline, Mark A; Gilbert, Elizabeth R

    2018-01-01

    The objective was to determine the effects of high-protein and high-fat diets, and fasting and refeeding, on appetite regulation in chicks. Day of hatch chicks were fed one of four diets: basal, high protein (25% crude protein), and 15 and 30% high fat (15 and 30% metabolizable energy derived from soybean oil, respectively), and assigned to one of three treatments at 4 days: (1) access to feed, (2) 3 hours of fasting, or (3) fasting followed by 1 hour of refeeding. The hypothalamus was collected, total RNA isolated, and mRNA abundance measured. Food intake was reduced in chicks fed the high-protein and high-fat diets. Agouti-related peptide, neuropeptide Y (NPY), NPY receptors 1, 2, and 5, melanocortin receptors 3 and 4 (MC3R and 4R, respectively), mesotocin, corticotropin-releasing factor (CRF), and CRF receptor sub-type 2 (CRFR2) mRNAs were greatest in chicks that consumed the basal diet. Refeeding was associated with increased MC3R mRNA in the high-protein diet group. CRFR2 mRNA was increased by fasting and refeeding in chicks that consumed the high-protein diet. Food intake and hypothalamic gene expression of some important appetite-associated factors were reduced in chicks fed the high-protein or high-fat diets. Fasting and refeeding accentuated several differences and results suggest that the CRF and melanocortin pathways are involved.

  8. Amylin blunts hyperphagia and reduces weight and fat gain during recovery in socially stressed rats

    Science.gov (United States)

    Smeltzer, Michael; Scott, Karen; Melhorn, Susan; Krause, Eric

    2012-01-01

    During recovery from social stress in a visible burrow system (VBS), during which a dominance hierarchy is formed among the males, rats display hyperphagia and gain weight preferentially as visceral adipose tissue. By proportionally increasing visceral adiposity, social stress may contribute to the establishment of metabolic disorder. Amylin was administered to rats fed ad libitum during recovery from VBS stress in an attempt to prevent hyperphagia and the resultant gain in body weight and fat mass. Amylin treatment reduced food intake, weight gain, and accumulation of fat mass in male burrow rats, but not in male controls that spent time housed with a single female rather than in the VBS. Amylin did not alter neuropeptide Y (NPY), agouti-related peptide (AgRP), or proopiomelanocortin (POMC) mRNA expression in the arcuate nucleus of the hypothalamus as measured at the end of the recovery period, nor did it affect plasma corticosterone or leptin. Amylin exerted most of its effect on food intake during the first few days of recovery, possibly through antagonism of NPY and/or increasing leptin sensitivity. The potential for chronic social stress to contribute to metabolic disorder is diminished by amylin treatment, though the neuroendocrine mechanisms behind this effect remain elusive. PMID:22832535

  9. Fish pigmentation and the melanocortin system.

    Science.gov (United States)

    Cal, Laura; Suarez-Bregua, Paula; Cerdá-Reverter, José Miguel; Braasch, Ingo; Rotllant, Josep

    2017-09-01

    The melanocortin system is a complex neuroendocrine signaling mechanism involved in numerous physiological processes in vertebrates, including pigmentation, steroidogenesis and metabolic control. This review focuses at one of its most fascinating function in fish, its regulatory role in the control of pigmentation, in which the melanocortin 1 receptor (Mc1r), its agonist α-melanocyte stimulating hormone (α-Msh), and the endogenous antagonist agouti signaling protein (Asip1) are the main players. Functional control of Mc1r, which is highly expressed in fish skin and whose activation stimulates melanin production and melanosome dispersion in fish melanophores, is considered a key mechanism for vertebrate pigment phenotypes. The α-Msh peptide, the most documented Mc1r agonist involved in pigmentation, is produced in the pituitary gland, activating melanin synthesis by binding to Mc1r in fish melanophores. Finally, Asip1 is the putative factor for establishing the evolutionarily conserved dorso-ventral pigment pattern found across vertebrates. However, we are just starting to understand how other melanocortin system components are acting in this complex regulatory network. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Skp2 controls adipocyte proliferation during the development of obesity.

    Science.gov (United States)

    Sakai, Tamon; Sakaue, Hiroshi; Nakamura, Takehiro; Okada, Mitsuru; Matsuki, Yasushi; Watanabe, Eijiro; Hiramatsu, Ryuji; Nakayama, Keiko; Nakayama, Keiichi I; Kasuga, Masato

    2007-01-19

    The increase in the mass of adipose tissue during the development of obesity can arise through an increase in cell size, an increase in cell number, or both. Here we show that long term maintenance of C57BL/6 mice on a high fat diet (for approximately 25 weeks) induces an initial increase in adipocyte size followed by an increase in adipocyte number in white adipose tissue. The latter effect was found to be accompanied by up-regulation of expression of the gene for the F-box protein Skp2 as well as by downregulation of the cyclin-dependent kinase inhibitor p27(Kip1), a principal target of the SCF(Skp2) ubiquitin ligase, in white adipose tissue. Ablation of Skp2 protected mice from the development of obesity induced either by a high fat diet or by the lethal yellow agouti (A(y)) mutation, and this protective action was due to inhibition of the increase in adipocyte number without an effect on adipocyte hypertrophy. The reduction in the number of adipocyte caused by Skp2 ablation also inhibited the development of obesity-related insulin resistance in the A(y) mutant mice, although the reduced number of beta cells and reduced level of insulin secretion in Skp2-deficient mice resulted in glucose intolerance. Our observations thus indicate that Skp2 controls adipocyte proliferation during the development of obesity.

  11. Frequencies of genes for coat colour and horns in Nordic cattle breeds

    Directory of Open Access Journals (Sweden)

    Lien Sigbjørn

    2000-11-01

    Full Text Available Abstract Gene frequencies of coat colour and horn types were assessed in 22 Nordic cattle breeds in a project aimed at establishing genetic profiles of the breeds under study. The coat colour loci yielding information on genetic variation were: extension, agouti, spotting, brindle, dun dilution and colour sided. The polled locus was assessed for two alleles. A profound variation between breeds was observed in the frequencies of both colour and horn alleles, with the older breeds generally showing greater variation in observed colour, horn types and segregating alleles than the modern breeds. The correspondence between the present genetic distance matrix and previous molecular marker distance matrices was low (r = 0.08 – 0.12. The branching pattern of a neighbour-joining tree disagreed to some extent with the molecular data structure. The current data indicates that 70% of the total genetic variation could be explained by differences between the breeds, suggesting a much greater breed differentiation than typically found at protein and microsatellite loci. The marked differentiation of the cattle breeds and observed disagreements with the results from the previous molecular data in the topology of the phylogenetic trees are most likely a result of selection on phenotypic characters analysed in this study.

  12. Hypothalamic actions of tumor necrosis factor alpha provide the thermogenic core for the wastage syndrome in cachexia.

    Science.gov (United States)

    Arruda, Ana Paula; Milanski, Marciane; Romanatto, Talita; Solon, Carina; Coope, Andressa; Alberici, Luciane C; Festuccia, William T; Hirabara, Sandro M; Ropelle, Eduardo; Curi, Rui; Carvalheira, José B; Vercesi, Aníbal E; Velloso, Licio A

    2010-02-01

    TNFalpha is an important mediator of catabolism in cachexia. Most of its effects have been characterized in peripheral tissues, such as skeletal muscle and fat. However, by acting directly in the hypothalamus, TNFalpha can activate thermogenesis and modulate food intake. Here we show that high concentration TNFalpha in the hypothalamus leads to increased O(2) consumption/CO(2) production, increased body temperature, and reduced caloric intake, resulting in loss of body mass. Most of the thermogenic response is produced by beta 3-adrenergic signaling to the brown adipose tissue (BAT), leading to increased BAT relative mass, reduction in BAT lipid quantity, and increased BAT mitochondria density. The expression of proteins involved in BAT thermogenesis, such as beta 3-adrenergic receptor, peroxisomal proliferator-activated receptor-gamma coactivator-1 alpha, and uncoupling protein-1, are increased. In the hypothalamus, TNFalpha produces reductions in neuropeptide Y, agouti gene-related peptide, proopiomelanocortin, and melanin-concentrating hormone, and increases CRH and TRH. The activity of the AMP-activated protein kinase signaling pathway is also decreased in the hypothalamus of TNFalpha-treated rats. Upon intracerebroventricular infliximab treatment, tumor-bearing and septic rats present a significantly increased survival. In addition, the systemic inhibition of beta 3-adrenergic signaling results in a reduced body mass loss and increased survival in septic rats. These data suggest hypothalamic TNFalpha action to be important mediator of the wastage syndrome in cachexia.

  13. A central thermogenic-like mechanism in feeding regulation: an interplay between arcuate nucleus T3 and UCP2.

    Science.gov (United States)

    Coppola, Anna; Liu, Zhong-Wu; Andrews, Zane B; Paradis, Eric; Roy, Marie-Claude; Friedman, Jeffrey M; Ricquier, Daniel; Richard, Denis; Horvath, Tamas L; Gao, Xiao-Bing; Diano, Sabrina

    2007-01-01

    The active thyroid hormone, triiodothyronine (T3), regulates mitochondrial uncoupling protein activity and related thermogenesis in peripheral tissues. Type 2 deiodinase (DII), an enzyme that catalyzes active thyroid hormone production, and mitochondrial uncoupling protein 2 (UCP2) are also present in the hypothalamic arcuate nucleus, where their interaction and physiological significance have not been explored. Here, we report that DII-producing glial cells are in direct apposition to neurons coexpressing neuropeptide Y (NPY), agouti-related protein (AgRP), and UCP2. Fasting increased DII activity and local thyroid hormone production in the arcuate nucleus in parallel with increased GDP-regulated UCP2-dependent mitochondrial uncoupling. Fasting-induced T3-mediated UCP2 activation resulted in mitochondrial proliferation in NPY/AgRP neurons, an event that was critical for increased excitability of these orexigenic neurons and consequent rebound feeding following food deprivation. These results reveal a physiological role for a thyroid-hormone-regulated mitochondrial uncoupling in hypothalamic neuronal networks.

  14. Energy Balance Regulating Neuropeptides Are Expressed through Pregnancy and Regulated by Interleukin-6 Deficiency in Mouse Placenta

    Science.gov (United States)

    Pazos, Patricia; Lima, Luis; Diéguez, Carlos; García, María C.

    2014-01-01

    The placenta produces a number of signaling molecules including metabolic and reproductive hormones as well as several inflammatory mediators. Among them, Interleukin-6 (IL-6), a well-known immune and metabolic regulator, acts peripherally modulating metabolic function and centrally increasing energy expenditure and reducing body fat. IL-6 interacts with key hypothalamic neuropeptidergic systems controlling energy homeostasis such as those producing the orexigenic/anabolic: neuropeptide Y (NPY) and agouti-related peptide (AgRP) and anorectic/catabolic neuropeptides: proopiomelanocortin (POMC) and cocaine and amphetamine regulated transcript (CART). Human and rat placenta have been identified as source of these neuropeptides, but their expression and regulation in murine placental tissues remain unknown. Therefore, placental mRNA levels of IL-6, NPY, AgRP, POMC, and CART at different pregnancy stages (gestational days 13, 15, and 18) were analyzed by real time PCR, as were the effect of IL-6 deficiency (IL-6 knockout mice) on their placental expression. Our results showed that placenta-derived neuropeptides were regulated by gestational age and IL-6 throughout the second half of mouse pregnancy. These data suggest that IL-6 may participate in the fine tune control of energy balance during pregnancy by extending its action as a metabolic signal to the main organ at the fetomaternal interface: the placenta. PMID:24744782

  15. A New Murine Model of Chronic Kidney Disease-Mineral and Bone Disorder

    Directory of Open Access Journals (Sweden)

    Bianca Frauscher

    2017-01-01

    Full Text Available Chronic kidney disease (CKD is associated with mineral and bone disorder (MBD, which is the main cause of the extensively increased cardiovascular mortality in the CKD population. We now aimed to establish a new murine experimental CKD-MBD model. Dilute brown non-Agouti (DBA/2 mice were fed with high-phosphate diet for 4 (HPD4 or 7 (HPD7 days, then with standard chow diet (SCD and subsequently followed until day 84. They were compared to DBA/2 mice maintained on SCD during the whole study period. Both 4 and 7 days HPD-fed mice developed phosphate nephropathy with tubular atrophy, interstitial fibrosis, decreased glomerular filtration rate, and increased serum urea levels. The abdominal aorta of HPD-treated mice showed signs of media calcification. Histomorphometric analysis of HPD-treated mice showed decreased bone volume/tissue volume, low mineral apposition rate, and low bone formation rate as compared to SCD-fed mice, despite increased parathyroid hormone levels. Overall, the observed phenotype was more pronounced in the HPD7 group. In summary, we established a new, noninvasive, and therefore easy to perform reproducible CKD-MBD model, which showed media calcification, secondary hyperparathyroidism, and low-turnover bone disease.

  16. Sympathetic Neurotransmitters Modulate Osteoclastogenesis and Osteoclast Activity in the Context of Collagen-Induced Arthritis

    Science.gov (United States)

    Muschter, Dominique; Schäfer, Nicole; Stangl, Hubert; Straub, Rainer H.; Grässel, Susanne

    2015-01-01

    Excessive synovial osteoclastogenesis is a hallmark of rheumatoid arthritis (RA). Concomitantly, local synovial changes comprise neuronal components of the peripheral sympathetic nervous system. Here, we wanted to analyze if collagen-induced arthritis (CIA) alters bone marrow-derived macrophage (BMM) osteoclastogenesis and osteoclast activity, and how sympathetic neurotransmitters participate in this process. Therefore, BMMs from Dark Agouti rats at different CIA stages were differentiated into osteoclasts in vitro and osteoclast number, cathepsin K activity, matrix resorption and apoptosis were analyzed in the presence of acetylcholine (ACh), noradrenaline (NA) vasoactive intestinal peptide (VIP) and assay-dependent, adenylyl cyclase activator NKH477. We observed modulation of neurotransmitter receptor mRNA expression in CIA osteoclasts without affecting protein level. CIA stage-dependently altered marker gene expression associated with osteoclast differentiation and activity without affecting osteoclast number or activity. Neurotransmitter stimulation modulated osteoclast differentiation, apoptosis and activity. VIP, NA and adenylyl cyclase activator NKH477 inhibited cathepsin K activity and osteoclastogenesis (NKH477, 10-6M NA) whereas ACh mostly acted pro-osteoclastogenic. We conclude that CIA alone does not affect metabolism of in vitro generated osteoclasts whereas stimulation with NA, VIP plus specific activation of adenylyl cyclase induced anti-resorptive effects probably mediated via cAMP signaling. Contrary, we suggest pro-osteoclastogenic and pro-resorptive properties of ACh mediated via muscarinic receptors. PMID:26431344

  17. AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus.

    Science.gov (United States)

    Minokoshi, Yasuhiko; Alquier, Thierry; Furukawa, Noboru; Kim, Yong-Bum; Lee, Anna; Xue, Bingzhong; Mu, James; Foufelle, Fabienne; Ferré, Pascal; Birnbaum, Morris J; Stuck, Bettina J; Kahn, Barbara B

    2004-04-01

    Obesity is an epidemic in Western society, and causes rapidly accelerating rates of type 2 diabetes and cardiovascular disease. The evolutionarily conserved serine/threonine kinase, AMP-activated protein kinase (AMPK), functions as a 'fuel gauge' to monitor cellular energy status. We investigated the potential role of AMPK in the hypothalamus in the regulation of food intake. Here we report that AMPK activity is inhibited in arcuate and paraventricular hypothalamus (PVH) by the anorexigenic hormone leptin, and in multiple hypothalamic regions by insulin, high glucose and refeeding. A melanocortin receptor agonist, a potent anorexigen, decreases AMPK activity in PVH, whereas agouti-related protein, an orexigen, increases AMPK activity. Melanocortin receptor signalling is required for leptin and refeeding effects on AMPK in PVH. Dominant negative AMPK expression in the hypothalamus is sufficient to reduce food intake and body weight, whereas constitutively active AMPK increases both. Alterations of hypothalamic AMPK activity augment changes in arcuate neuropeptide expression induced by fasting and feeding. Furthermore, inhibition of hypothalamic AMPK is necessary for leptin's effects on food intake and body weight, as constitutively active AMPK blocks these effects. Thus, hypothalamic AMPK plays a critical role in hormonal and nutrient-derived anorexigenic and orexigenic signals and in energy balance.

  18. Interleukin-7, a new cytokine targeting the mouse hypothalamic arcuate nucleus: role in body weight and food intake regulation.

    Science.gov (United States)

    Macia, Laurence; Viltart, Odile; Delacre, Myriam; Sachot, Christelle; Héliot, Laurent; Di Santo, James P; Wolowczuk, Isabelle

    2010-04-01

    Body weight is controlled through peripheral (white adipose tissue) and central (mainly hypothalamus) mechanisms. We have recently obtained evidence that overexpression of interleukin (IL)-7, a critical cytokine involved in lymphopoiesis, can protect against the development of diet-induced obesity in mice. Here we assessed whether IL-7 mediated its effects by modulating hypothalamic function. Acute subcutaneous injection of IL-7 prevented monosodium glutamate-induced obesity, this being correlated with partial protection against cell death in the hypothalamic arcuate nucleus (ARC). Moreover, we showed that IL-7 activated hypothalamic areas involved in regulation of feeding behavior, as indicated by induction of the activation marker c-Fos in neural cells located in the ventromedial part of the ARC and by inhibition of food intake after fasting. Both chains of the IL-7 receptor (IL-7Ralpha and gamma(c)) were expressed in the ARC and IL-7 injection induced STAT-3 phosphorylation in this area. Finally, we established that IL-7 modulated the expression of neuropeptides that tune food intake, with a stimulatory effect on the expression of pro-opiomelanocortin and an inhibitory effect on agouti-related peptide expression in accordance with IL-7 promoting anorectic effects. These results suggest that the immunomodulatory cytokine IL-7 plays an important and unappreciated role in hypothalamic body weight regulation.

  19. Differentiation of hypothalamic-like neurons from human pluripotent stem cells.

    Science.gov (United States)

    Wang, Liheng; Meece, Kana; Williams, Damian J; Lo, Kinyui Alice; Zimmer, Matthew; Heinrich, Garrett; Martin Carli, Jayne; Leduc, Charles A; Sun, Lei; Zeltser, Lori M; Freeby, Matthew; Goland, Robin; Tsang, Stephen H; Wardlaw, Sharon L; Egli, Dieter; Leibel, Rudolph L

    2015-02-01

    The hypothalamus is the central regulator of systemic energy homeostasis, and its dysfunction can result in extreme body weight alterations. Insights into the complex cellular physiology of this region are critical to the understanding of obesity pathogenesis; however, human hypothalamic cells are largely inaccessible for direct study. Here, we developed a protocol for efficient generation of hypothalamic neurons from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) obtained from patients with monogenetic forms of obesity. Combined early activation of sonic hedgehog signaling followed by timed NOTCH inhibition in human ESCs/iPSCs resulted in efficient conversion into hypothalamic NKX2.1+ precursors. Application of a NOTCH inhibitor and brain-derived neurotrophic factor (BDNF) further directed the cells into arcuate nucleus hypothalamic-like neurons that express hypothalamic neuron markers proopiomelanocortin (POMC), neuropeptide Y (NPY), agouti-related peptide (AGRP), somatostatin, and dopamine. These hypothalamic-like neurons accounted for over 90% of differentiated cells and exhibited transcriptional profiles defined by a hypothalamic-specific gene expression signature that lacked pituitary markers. Importantly, these cells displayed hypothalamic neuron characteristics, including production and secretion of neuropeptides and increased p-AKT and p-STAT3 in response to insulin and leptin. Our results suggest that these hypothalamic-like neurons have potential for further investigation of the neurophysiology of body weight regulation and evaluation of therapeutic targets for obesity.

  20. Astrocytes modulate distribution and neuronal signaling of leptin in the hypothalamus of obese A vy mice.

    Science.gov (United States)

    Pan, Weihong; Hsuchou, Hung; Xu, Changlei; Wu, Xiaojun; Bouret, Sebastien G; Kastin, Abba J

    2011-03-01

    We tested the hypothesis that astrocytic activity modulates neuronal uptake and signaling of leptin in the adult-onset obese agouti viable yellow (A vy) mouse. In the immunohistochemical study, A vy mice were pretreated with the astrocyte metabolic inhibitor fluorocitrate or phosphate-buffered saline (PBS) vehicle intracerebroventricularly (icv) followed 1 h later by Alexa568-leptin. Confocal microscopy showed that fluorocitrate pretreatment reduced astrocytic uptake of Alexa568-leptin 30 min after icv while increasing neuronal uptake in the arcuate nucleus and dorsomedial hypothalamus. Fluorocitrate also induced mild astrogliosis and moderately increased pSTAT3 immunopositive neurons in response to Alexa568-leptin in the dorsomedial hypothalamus. In the Western blotting study, A vy mice were pretreated with either PBS or fluorocitrate, and received PBS or leptin 1 h later followed by determination of pSTAT3 and GFAP expression an additional 30 min afterward. The results show that fluorocitrate induced a mild pSTAT3 activation but attenuated leptin-induced pSTAT3 activation and decreased GFAP expression independently of leptin treatment. We conclude that inhibition of astrocytic activity resulted in enhanced neuronal leptin uptake and signaling. This suggests opposite roles of astrocytes and neurons in leptin's actions in the A vy mouse with adult-onset obesity.

  1. Resveratrol, purified from the stem of Vitis coignetiae Pulliat, inhibits food intake in C57BL/6J Mice.

    Science.gov (United States)

    Kim, Su-Jin; Lee, Yong Hwa; Han, Man-Deuk; Mar, Woongchon; Kim, Won-Ki; Nam, Kung-Woo

    2010-05-01

    Neuropeptide Y (NPY) and agouti-related protein (AgRP) have powerful stimulatory effects on food intake, which suggests that the downregulation of brain NPY or AgRP may help reduce obesity and diabetes by inhibiting food intake. To search for active compounds that inhibit NPY and AgRP expression, we made two luciferase reporter assay systems consisting of NPY and AgRP promoter-driven luciferase genes, together with the puromycin resistance gene, in a plasmid vector. Each plasmid was permanently transfected into N29-4 neuronal cells. Using the systems, resveratrol was purified from the stem of Vitis coignetiae Pulliat by activityguided fractionation. Resveratrol downregulated NPY and AgRP promoter-driven luciferase activity in a dose-dependent manner. The inhibitory concentrations (IC(50), 50% inhibition) of resveratrol against pNPY-luc and pAgRP-luc activities were 8.9 microM and 8.0 microM, respectively. Furthermore, one-time intraperitoneal injection of resveratrol (100 mg/kg) suppressed 20.0% and 17.2% of food intake during 24 and 48 h, respectively. These results indicated that resveratrol inhibited food intake, which may be related to the downregulation of NPY and AgRP gene expression.

  2. Arcuate AgRP neurons and the regulation of energy balance.

    Science.gov (United States)

    Cansell, Céline; Denis, Raphaël G P; Joly-Amado, Aurélie; Castel, Julien; Luquet, Serge

    2012-01-01

    The arcuate nucleus of the hypothalamus contains at least two populations of neurons that continuously monitor signals reflecting energy status and promote the appropriate behavioral and metabolic responses to changes in energy demand. Activation of neurons making pro-opiomelanocortin (POMC) decreases food intake and increases energy expenditure through activation of G protein-coupled melanocortin receptors via the release of α-melanocyte-stimulating hormone. Until recently, the prevailing idea was that the neighboring neurons [agouti-related protein (AgRP) neurons] co-expressing the orexigenic neuropeptides, AgRP, and neuropeptide Y increase feeding by opposing the anorexigenic actions of the POMC neurons. However, it has now been demonstrated that only AgRP neurons activation - not POMC neurons inhibition - is necessary and sufficient to promote feeding. Projections of AgRP-expressing axons innervate mesolimbic, midbrain, and pontine structures where they regulate feeding and feeding-independent functions such as reward or peripheral nutrient partitioning. AgRP neurons also make gamma aminobutyric acid , which is now thought to mediate many of critical functions of these neurons in a melanocortin-independent manner and on a timescale compatible with neuromodulation.

  3. Subcutaneous administration of leptin normalizes fasting plasma glucose in obese type 2 diabetic UCD-T2DM rats.

    Science.gov (United States)

    Cummings, Bethany P; Bettaieb, Ahmed; Graham, James L; Stanhope, Kimber L; Dill, Riva; Morton, Gregory J; Haj, Fawaz G; Havel, Peter J

    2011-08-30

    Leptin has been shown to reduce hyperglycemia in rodent models of type 1 diabetes. We investigated the effects of leptin administration in University of California, Davis, type 2 diabetes mellitus (UCD-T2DM) rats, which develop adult-onset polygenic obesity and type 2 diabetes. Animals that had been diabetic for 2 mo were treated with s.c. injections of saline (control) or murine leptin (0.5 mg/kg) twice daily for 1 mo. Control rats were pair-fed to leptin-treated animals. Treatment with leptin normalized fasting plasma glucose and was accompanied by lowered HbA1c, plasma glucagon, and triglyceride concentrations and expression of hepatic gluconeogenic enzymes compared with vehicle (P inhibition factor 2α (PERK-eIF2α) arm of ER stress in liver, skeletal muscle, and adipose tissue as well as increased pro-opiomelanocortin and decreased agouti-related peptide in the hypothalamus. In contrast, several markers of inflammation/immune function were elevated with leptin treatment in the same tissues (P < 0.05), suggesting that the leptin-mediated increase of insulin sensitivity was not attributable to decreased inflammation. Thus, leptin administration improves insulin sensitivity and normalizes fasting plasma glucose in diabetic UCD-T2DM rats, independent of energy intake, via peripheral and possibly centrally mediated actions, in part by decreasing circulating glucagon and ER stress.

  4. Arcuate AgRP neurons and the regulation of energy balance

    Directory of Open Access Journals (Sweden)

    Céline eCansell

    2012-12-01

    Full Text Available The arcuate nucleus of the hypothalamus contains at least two crucial populations of neurons that continuously monitor signals reflecting energy status and promote the appropriate behavioral and metabolic responses to changes in energy demand. Neurons making pro-opiomelanocortin (POMC decrease food intake and increase energy expenditure through activation of G protein-coupled receptors melanocortin receptors (MCR via the release of a-melanocyte stimulating hormone. A prevailing idea until recently was that the neighboring neurons expressing the orexigenic neuropeptides, agouti-related protein (AgRP and neuropeptide Y (NPY (AgRP neurons increased feeding by opposing the anorexigenic actions of the POMC neurons. AgRP neurons activation but not POMC neurons inhibition was recently demonstrated to be necessary and sufficient to promote feeding. AgRP expressing axons were identified in mesolimbic, midbrain and pontine structure where they regulate feeding but also feeding-independent functions such as reward or peripheral nutrient partitioning. Post-synaptic Gamma aminobutyric acid (GABA, lasting in a timeline similar to neuromodulation, was identified as the core mechanism by which hunger-activated neurons regulate feeding and non-food related processes in a melanocortin independent manner.

  5. Stearoyl-CoA desaturase-1 deficiency attenuates obesity and insulin resistance in leptin-resistant obese mice.

    Science.gov (United States)

    Miyazaki, Makoto; Sampath, Harini; Liu, Xueqing; Flowers, Matthew T; Chu, Kiki; Dobrzyn, Agnieszka; Ntambi, James M

    2009-03-20

    Obesity and adiposity greatly increase the risk for secondary conditions such as insulin resistance. Mice deficient in the enzyme stearoyl-CoA desaturase-1 (SCD1) are lean and protected from diet-induced obesity and insulin resistance. In order to determine the effect of SCD1 deficiency on various mouse models of obesity, we introduced a global deletion of the Scd1 gene into leptin-deficient ob/ob mice, leptin-resistant Agouti (A(y)/a) mice, and high-fat diet-fed obese (DIO) mice. SCD1 deficiency lowered body weight, adiposity, hepatic lipid accumulation, and hepatic lipogenic gene expression in all three mouse models. However, glucose tolerance, insulin, and leptin sensitivity were improved by SCD1 deficiency only in A(y)/a and DIO mice, but not ob/ob mice. These data uncouple the effects of SCD1 deficiency on weight loss from those on insulin sensitivity and suggest a beneficial effect of SCD1 inhibition on insulin sensitivity in obese mice that express a functional leptin gene.

  6. Insulin resistance vs. hyperinsulinemia in hypertension: insulin regulation of Ca2+ transport and Ca(2+)-regulation of insulin sensitivity.

    Science.gov (United States)

    Zemel, M B

    1995-06-01

    Hypertension in obesity and insulin resistance has been attributed to insulin stimulation of sympathetic neural output and renal sodium retention. However, recent data demonstrates a significant vasodilatory effect of insulin and suggests that vascular smooth muscle resistance to this action may instead be the cause of hypertension in insulin resistance. This concept is supported by the observation that pharmacological amplification of peripheral insulin sensitivity results in reduced arterial pressure. Insulin attenuates vasoconstrictor responses to pressor agonists and accelerates vascular smooth muscle relaxation, while these effects are blunted in obesity and insulin resistance. Insulin regulation of vasoconstriction and vascular relaxation appears to be secondary to regulation of intracellular Ca2+ ([Ca2+]i), as insulin attenuates both voltage- and receptor-mediated Ca2+ influx and stimulates both the transcription and activity of Ca(2+)-ATPase in vascular smooth muscle cells. Further, these effects are also blunted in insulin resistance. Although [Ca2+]i plays a poorly understood role in insulin signalling, increases beyond an optimal range results in impaired insulin sensitivity, possibly by Ca(2+)-inhibition of insulin-induced dephosphorylation of insulin-sensitive substrates. Consistent with this concept, ectopic overexpression of the agouti gene in the viable yellow (Avy) mouse results in increased skeletal myocyte [Ca2+]i. Accordingly, increased [Ca2+]i in primary insulin target tissues appears to result in peripheral insulin resistance which then results in aberrant regulation of vascular smooth muscle [Ca2+]i and increases in arterial pressure.

  7. Hypothalamic ceramide levels regulated by CPT1C mediate the orexigenic effect of ghrelin.

    Science.gov (United States)

    Ramírez, Sara; Martins, Luís; Jacas, Jordi; Carrasco, Patricia; Pozo, Macarena; Clotet, Josep; Serra, Dolors; Hegardt, Fausto G; Diéguez, Carlos; López, Miguel; Casals, Núria

    2013-07-01

    Recent data suggest that ghrelin exerts its orexigenic action through regulation of hypothalamic AMP-activated protein kinase pathway, leading to a decline in malonyl-CoA levels and desinhibition of carnitine palmitoyltransferase 1A (CPT1A), which increases mitochondrial fatty acid oxidation and ultimately enhances the expression of the orexigenic neuropeptides agouti-related protein (AgRP) and neuropeptide Y (NPY). However, it is unclear whether the brain-specific isoform CPT1C, which is located in the endoplasmic reticulum of neurons, may play a role in this action. Here, we demonstrate that the orexigenic action of ghrelin is totally blunted in CPT1C knockout (KO) mice, despite having the canonical ghrelin signaling pathway activated. We also demonstrate that ghrelin elicits a marked upregulation of hypothalamic C18:0 ceramide levels mediated by CPT1C. Notably, central inhibition of ceramide synthesis with myriocin negated the orexigenic action of ghrelin and normalized the levels of AgRP and NPY, as well as their key transcription factors phosphorylated cAMP-response element-binding protein and forkhead box O1. Finally, central treatment with ceramide induced food intake and orexigenic neuropeptides expression in CPT1C KO mice. Overall, these data indicate that, in addition to formerly reported mechanisms, ghrelin also induces food intake through regulation of hypothalamic CPT1C and ceramide metabolism, a finding of potential importance for the understanding and treatment of obesity.

  8. FAS inhibitor cerulenin reduces food intake and melanocortin receptor gene expression without modulating the other (an)orexigenic neuropeptides in chickens.

    Science.gov (United States)

    Dridi, Sami; Ververken, Cedric; Hillgartner, F Bradley; Arckens, Lutgarde; Lutgarde, Arckens; Van der Gucht, Estel; Cnops, Lieselotte; Decuypere, Eddy; Buyse, Johan

    2006-07-01

    Cerulenin, a natural fatty acid synthase (FAS) inhibitor, and its synthetic analog C75 are hypothesized to alter the metabolism of neurons in the hypothalamus that regulate ingestive behavior to cause a profound decrease of food intake and an increase in metabolic rate, leading to body weight loss. The bulk of data exclusively originates from mammals (rodents); however, such effects are currently lacking in nonmammalian species. We have, therefore, addressed this issue in broiler chickens because this species is selected for high growth rate and high food intake and is prone to obesity. First, we demonstrate that FAS messenger and protein are expressed in the hypothalamus of chickens. FAS immunoreactivity was detected in a number of brain regions, including the nucleus paraventricularis magnocellularis and the nucleus infundibuli hypothalami, the avian equivalent of the mammalian arcuate nucleus, suggesting that FAS may be involved in the regulation of food intake. Second, we show that hypothalamic FAS gene expression was significantly (P inhibition of fatty acid synthesis on food intake, we administered cerulenin by intravenous injections (15 mg/kg) to 2-wk-old broiler chickens. Cerulenin administration significantly reduced food intake by 23 to 34% (P agouti gene-related peptide, orexin, and orexin receptor) and anorexigenic (pro-opiomelanocortin and corticotropin-releasing hormone) neuropeptide mRNA levels remained unchanged after cerulenin treatment. These results suggest that the catabolic effect of cerulenin in chickens may be mediated through the melanocortin system rather than the other neuropeptides known to be involved in food intake regulation.

  9. The role of liver fructose-1,6-bisphosphatase in regulating appetite and adiposity.

    Science.gov (United States)

    Visinoni, Sherley; Khalid, Nurul Fathiah Izzati; Joannides, Christos N; Shulkes, Arthur; Yim, Mildred; Whitehead, Jon; Tiganis, Tony; Lamont, Benjamin J; Favaloro, Jenny M; Proietto, Joseph; Andrikopoulos, Sofianos; Fam, Barbara C

    2012-05-01

    Liver fructose-1,6-bisphosphatase (FBPase) is a regulatory enzyme in gluconeogenesis that is elevated by obesity and dietary fat intake. Whether FBPase functions only to regulate glucose or has other metabolic consequences is not clear; therefore, the aim of this study was to determine the importance of liver FBPase in body weight regulation. To this end we performed comprehensive physiologic and biochemical assessments of energy balance in liver-specific transgenic FBPase mice and negative control littermates of both sexes. In addition, hepatic branch vagotomies and pharmacologic inhibition studies were performed to confirm the role of FBPase. Compared with negative littermates, liver-specific FBPase transgenic mice had 50% less adiposity and ate 15% less food but did not have altered energy expenditure. The reduced food consumption was associated with increased circulating leptin and cholecystokinin, elevated fatty acid oxidation, and 3-β-hydroxybutyrate ketone levels, and reduced appetite-stimulating neuropeptides, neuropeptide Y and Agouti-related peptide. Hepatic branch vagotomy and direct pharmacologic inhibition of FBPase in transgenic mice both returned food intake and body weight to the negative littermates. This is the first study to identify liver FBPase as a previously unknown regulator of appetite and adiposity and describes a novel process by which the liver participates in body weight regulation.

  10. Palatability Can Drive Feeding Independent of AgRP Neurons.

    Science.gov (United States)

    Denis, Raphaël G P; Joly-Amado, Aurélie; Webber, Emily; Langlet, Fanny; Schaeffer, Marie; Padilla, Stéphanie L; Cansell, Céline; Dehouck, Bénédicte; Castel, Julien; Delbès, Anne-Sophie; Martinez, Sarah; Lacombe, Amélie; Rouch, Claude; Kassis, Nadim; Fehrentz, Jean-Alain; Martinez, Jean; Verdié, Pascal; Hnasko, Thomas S; Palmiter, Richard D; Krashes, Michael J; Güler, Ali D; Magnan, Christophe; Luquet, Serge

    2015-10-06

    Feeding behavior is exquisitely regulated by homeostatic and hedonic neural substrates that integrate energy demand as well as the reinforcing and rewarding aspects of food. Understanding the net contribution of homeostatic and reward-driven feeding has become critical because of the ubiquitous source of energy-dense foods and the consequent obesity epidemic. Hypothalamic agouti-related peptide-secreting neurons (AgRP neurons) provide the primary orexigenic drive of homeostatic feeding. Using models of neuronal inhibition or ablation, we demonstrate that the feeding response to a fast ghrelin or serotonin receptor agonist relies on AgRP neurons. However, when palatable food is provided, AgRP neurons are dispensable for an appropriate feeding response. In addition, AgRP-ablated mice present exacerbated stress-induced anorexia and palatable food intake--a hallmark of comfort feeding. These results suggest that, when AgRP neuron activity is impaired, neural circuits sensitive to emotion and stress are engaged and modulated by food palatability and dopamine signaling. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. FoxO1 target Gpr17 activates AgRP neurons to regulate food intake.

    Science.gov (United States)

    Ren, Hongxia; Orozco, Ian J; Su, Ya; Suyama, Shigetomo; Gutiérrez-Juárez, Roger; Horvath, Tamas L; Wardlaw, Sharon L; Plum, Leona; Arancio, Ottavio; Accili, Domenico

    2012-06-08

    Hypothalamic neurons expressing Agouti-related peptide (AgRP) are critical for initiating food intake, but druggable biochemical pathways that control this response remain elusive. Thus, genetic ablation of insulin or leptin signaling in AgRP neurons is predicted to reduce satiety but fails to do so. FoxO1 is a shared mediator of both pathways, and its inhibition is required to induce satiety. Accordingly, FoxO1 ablation in AgRP neurons of mice results in reduced food intake, leanness, improved glucose homeostasis, and increased sensitivity to insulin and leptin. Expression profiling of flow-sorted FoxO1-deficient AgRP neurons identifies G-protein-coupled receptor Gpr17 as a FoxO1 target whose expression is regulated by nutritional status. Intracerebroventricular injection of Gpr17 agonists induces food intake, whereas Gpr17 antagonist cangrelor curtails it. These effects are absent in Agrp-Foxo1 knockouts, suggesting that pharmacological modulation of this pathway has therapeutic potential to treat obesity. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. 1alpha,25-Dihydroxyvitamin D3 modulates human adipocyte metabolism via nongenomic action.

    Science.gov (United States)

    Shi, H; Norman, A W; Okamura, W H; Sen, A; Zemel, M B

    2001-12-01

    We reported recently that suppression of the renal 1alpha,25-dihyroxyvitamin D3 (1lpha,25-(OH)2-D3) production in aP2-agouti transgenic mice by increasing dietary calcium decreases adipocyte intracellular Ca2+ ([Ca2+]i), stimulates lipolysis, inhibits lipogenesis, and reduces adiposity. However, it was not clear whether this modulation of adipocyte metabolism by dietary calcium is a direct effect of inhibition of 1alpha,25-(OH)2-D3-induced [Ca2+]i. Accordingly, we have now evaluated the direct role of 1alpha,25-(OH)2-D3. Human adipocytes exhibited a 1alpha,25-(OH)2-D3 dose-responsive (1-50 nM) increase in [Ca2+]i (Pinhibition of isoproterenol-stimulated lipolysis (Pinhibiting basal lipolysis (Pinhibition of 1alpha,25-(OH)2-D3-induced [Ca2+]i may contribute to an anti-obesity effect of dietary calcium, and the mVDR may represent an important target for obesity.

  13. 5-HT inhibition of rat insulin 2 promoter Cre recombinase transgene and proopiomelanocortin neuron excitability in the mouse arcuate nucleus.

    Science.gov (United States)

    Hisadome, K; Smith, M A; Choudhury, A I; Claret, M; Withers, D J; Ashford, M L J

    2009-03-03

    A number of anti-obesity agents have been developed that enhance hypothalamic 5-HT transmission. Various studies have demonstrated that arcuate neurons, which express proopiomelanocortin peptides (POMC neurons), and neuropeptide Y with agouti-related protein (NPY/AgRP) neurons, are components of the hypothalamic circuits responsible for energy homeostasis. An additional arcuate neuron population, rat insulin 2 promoter Cre recombinase transgene (RIPCre) neurons, has recently been implicated in hypothalamic melanocortin circuits involved in energy balance. It is currently unclear how 5-HT modifies neuron excitability in these local arcuate neuronal circuits. We show that 5-HT alters the excitability of the majority of mouse arcuate RIPCre neurons, by either hyperpolarization and inhibition or depolarization and excitation. RIPCre neurons sensitive to 5-HT, predominantly exhibit hyperpolarization and pharmacological studies indicate that inhibition of neuronal firing is likely to be through 5-HT(1F) receptors increasing current through a voltage-dependent potassium conductance. Indeed, 5-HT(1F) receptor immunoreactivity co-localizes with RIPCre green fluorescent protein expression. A minority population of POMC neurons also respond to 5-HT by hyperpolarization, and this appears to be mediated by the same receptor-channel mechanism. As neither POMC nor RIPCre neuronal populations display a common electrical response to 5-HT, this may indicate that sub-divisions of POMC and RIPCre neurons exist, perhaps serving different outputs.

  14. Intracerebroventricular administration of conjugated linoleic acid (CLA) inhibits food intake by decreasing gene expression of NPY and AgRP.

    Science.gov (United States)

    Cao, Zi-Peng; Wang, Feng; Xiang, Xue-Song; Cao, Rui; Zhang, Wen-Bin; Gao, Shuang-Bin

    2007-05-18

    Dietary conjugated linoleic acid (CLA) has been investigated for its beneficial effects on disease prevention and treatment, and now obesity is one of the most perspective researching highlights. In a variety of experimental models, the results of studies on the effects of CLA on food intakes are somewhat inconsistent. Our experiment was conducted to extend these observations to hypothalamus and other regions within the central nervous system so that the mechanism of the actions of CLA might be more easily elucidated. In the experiment, a permanent cannula was inserted into the lateral ventricle of each rat. For the experiment, animals received intracerebroventricular injections of either 150nmol (n=16) CLA, or LA as non-conjugated control, or normal saline as vehicle. Hypothalamus and blood samples were collected at the 2nd, 4th, 8th, and 14th day. The results show that CLA in cerebral ventricle can inhibit food intake of experimented rats and this inhibition is related with the decreased expression of neuropeptides Y (NPY) and agouti-related protein (AgRP). The circulating leptin level was also increased by this tentative treatment (2.94+/-0.71 versus 1.18+/-0.18ng/ml). However, the glucose metabolism was not affected by ICV CLA. It is concluded that CLA in brain can inhibit the appetite of rats through the mechanism of decreasing the expression of NPY and AgRP.

  15. Inhibition of hypothalamic Foxo1 expression reduced food intake in diet-induced obesity rats.

    Science.gov (United States)

    Ropelle, Eduardo R; Pauli, José R; Prada, Patrícia; Cintra, Dennys E; Rocha, Guilherme Z; Moraes, Juliana C; Frederico, Marisa J S; da Luz, Gabrielle; Pinho, Ricardo A; Carvalheira, José B C; Velloso, Licio A; Saad, Mario A; De Souza, Cláudio T

    2009-05-15

    Insulin signalling in the hypothalamus plays a role in maintaining body weight. The forkhead transcription factor Foxo1 is an important mediator of insulin signalling in the hypothalamus. Foxo1 stimulates the transcription of the orexigenic neuropeptide Y and Agouti-related protein through the phosphatidylinositol-3-kinase/Akt signalling pathway, but the role of hypothalamic Foxo1 in insulin resistance and obesity remains unclear. Here, we identify that a high-fat diet impaired insulin-induced hypothalamic Foxo1 phosphorylation and degradation, increasing the nuclear Foxo1 activity and hyperphagic response in rats. Thus, we investigated the effects of the intracerebroventricular (i.c.v.) microinfusion of Foxo1-antisense oligonucleotide (Foxo1-ASO) and evaluated the food consumption and weight gain in normal and diet-induced obese (DIO) rats. Three days of Foxo1-ASO microinfusion reduced the hypothalamic Foxo1 expression by about 85%. i.c.v. infusion of Foxo1-ASO reduced the cumulative food intake (21%), body weight change (28%), epididymal fat pad weight (22%) and fasting serum insulin levels (19%) and increased the insulin sensitivity (34%) in DIO but not in control animals. Collectively, these data showed that the Foxo1-ASO treatment blocked the orexigenic effects of Foxo1 and prevented the hyperphagic response in obese rats. Thus, pharmacological manipulation of Foxo1 may be used to prevent or treat obesity.

  16. Ribosomal S6K1 in POMC and AgRP Neurons Regulates Glucose Homeostasis but Not Feeding Behavior in Mice

    Directory of Open Access Journals (Sweden)

    Mark A. Smith

    2015-04-01

    Full Text Available Hypothalamic ribosomal S6K1 has been suggested as a point of convergence for hormonal and nutrient signals in the regulation of feeding behavior, bodyweight, and glucose metabolism. However, the long-term effects of manipulating hypothalamic S6K1 signaling on energy homeostasis and the cellular mechanisms underlying these roles are unclear. We therefore inactivated S6K1 in pro-opiomelanocortin (POMC and agouti-related protein (AgRP neurons, key regulators of energy homeostasis, but in contrast to the current view, we found no evidence that S6K1 regulates food intake and bodyweight. In contrast, S6K1 signaling in POMC neurons regulated hepatic glucose production and peripheral lipid metabolism and modulated neuronal excitability. S6K1 signaling in AgRP neurons regulated skeletal muscle insulin sensitivity and was required for glucose sensing by these neurons. Our findings suggest that S6K1 signaling is not a general integrator of energy homeostasis in the mediobasal hypothalamus but has distinct roles in the regulation of glucose homeostasis by POMC and AgRP neurons.

  17. Ribosomal S6K1 in POMC and AgRP Neurons Regulates Glucose Homeostasis but Not Feeding Behavior in Mice.

    Science.gov (United States)

    Smith, Mark A; Katsouri, Loukia; Irvine, Elaine E; Hankir, Mohammed K; Pedroni, Silvia M A; Voshol, Peter J; Gordon, Matthew W; Choudhury, Agharul I; Woods, Angela; Vidal-Puig, Antonio; Carling, David; Withers, Dominic J

    2015-04-21

    Hypothalamic ribosomal S6K1 has been suggested as a point of convergence for hormonal and nutrient signals in the regulation of feeding behavior, bodyweight, and glucose metabolism. However, the long-term effects of manipulating hypothalamic S6K1 signaling on energy homeostasis and the cellular mechanisms underlying these roles are unclear. We therefore inactivated S6K1 in pro-opiomelanocortin (POMC) and agouti-related protein (AgRP) neurons, key regulators of energy homeostasis, but in contrast to the current view, we found no evidence that S6K1 regulates food intake and bodyweight. In contrast, S6K1 signaling in POMC neurons regulated hepatic glucose production and peripheral lipid metabolism and modulated neuronal excitability. S6K1 signaling in AgRP neurons regulated skeletal muscle insulin sensitivity and was required for glucose sensing by these neurons. Our findings suggest that S6K1 signaling is not a general integrator of energy homeostasis in the mediobasal hypothalamus but has distinct roles in the regulation of glucose homeostasis by POMC and AgRP neurons. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Investigating the role of the melanocortin-1 receptor gene in an extreme case of microgeographical variation in the pattern of melanin-based plumage pigmentation.

    Science.gov (United States)

    Bourgeois, Yann X C; Bertrand, Joris A M; Thébaud, Christophe; Milá, Borja

    2012-01-01

    The Réunion grey white-eye (Zosterops borbonicus) is a single-island endemic passerine bird that exhibits striking geographically structured melanic polymorphism at a very small spatial scale. We investigated the genetic basis of this color polymorphism by testing whether the melanocortin-1 receptor (MC1R), a gene often involved in natural melanic polymorphism in birds, was associated with the observed plumage variation. Although we found three non-synonymous mutations, we detected no association between MC1R variants and color morphs, and the main amino-acid variant found in the Réunion grey white-eye was also present at high frequency in the Mauritius grey white-eye (Zosterops mauritianus), its sister species which shows no melanic polymorphism. In addition, neutrality tests and analysis of population structure did not reveal any obvious pattern of positive or balancing selection acting on MC1R. Altogether these results indicate that MC1R does not play a role in explaining the melanic variation observed in the Réunion grey white-eye. We propose that other genes such as POMC, Agouti or any other genes involved in pigment synthesis will need to be investigated in future studies if we are to understand how selection shapes complex patterns of melanin-based plumage pigmentation. All sequences submitted to Genbank. Accession number: JX914505 to JX914564.

  19. Role of hypothalamic melanocortin system in adaptation of food intake to food protein increase in mice.

    Directory of Open Access Journals (Sweden)

    Bruno Pillot

    Full Text Available The hypothalamic melanocortin system--the melanocortin receptor of type 4 (MC4R and its ligands: α-melanin-stimulating hormone (α-MSH, agonist, inducing hypophagia, and agouti-related protein (AgRP, antagonist, inducing hyperphagia--is considered to play a central role in the control of food intake. We tested its implication in the mediation of the hunger-curbing effects of protein-enriched diets (PED in mice. Whereas there was a 20% decrease in food intake in mice fed on the PED, compared to mice fed on an isocaloric starch-enriched diet, there was a paradoxical decrease in expression of the hypothalamic proopiomelanocortin gene, precursor of α-MSH, and increase in expression of the gene encoding AgRP. The hypophagia effect of PED took place in mice with invalidation of either MC4R or POMC, and was even strengthened in mice with ablation of the AgRP-expressing neurons. These data strongly suggest that the hypothalamic melanocortin system does not mediate the hunger-curbing effects induced by changes in the macronutrient composition of food. Rather, the role of this system might be to defend the body against the variations in food intake generated by the nutritional environment.

  20. Goldfish Leptin-AI and Leptin-AII: Function and Central Mechanism in Feeding Control

    Directory of Open Access Journals (Sweden)

    Ai-Fen Yan

    2016-05-01

    Full Text Available In mammals, leptin is a peripheral satiety factor that inhibits feeding by regulating a variety of appetite-related hormones in the brain. However, most of the previous studies examining leptin in fish feeding were performed with mammalian leptins, which share very low sequence homologies with fish leptins. To elucidate the function and mechanism of endogenous fish leptins in feeding regulation, recombinant goldfish leptin-AI and leptin-AII were expressed in methylotrophic yeast and purified by immobilized metal ion affinity chromatography (IMAC. By intraperitoneal (IP injection, both leptin-AI and leptin-AII were shown to inhibit the feeding behavior and to reduce the food consumption of goldfish in 2 h. In addition, co-treatment of leptin-AI or leptin-AII could block the feeding behavior and reduce the food consumption induced by neuropeptide Y (NPY injection. High levels of leptin receptor (lepR mRNA were detected in the hypothalamus, telencephalon, optic tectum and cerebellum of the goldfish brain. The appetite inhibitory effects of leptins were mediated by downregulating the mRNA levels of orexigenic NPY, agouti-related peptide (AgRP and orexin and upregulating the mRNA levels of anorexigenic cocaine-amphetamine-regulated transcript (CART, cholecystokinin (CCK, melanin-concentrating hormone (MCH and proopiomelanocortin (POMC in different areas of the goldfish brain. Our study, as a whole, provides new insights into the functions and mechanisms of leptins in appetite control in a fish model.

  1. Melanocortin 1 Receptor: Structure, Function and Regulation

    Directory of Open Access Journals (Sweden)

    Erin Marissa Wolf Horrell

    2016-05-01

    Full Text Available The melanocortin 1 receptor (MC1R is a melanocytic Gs protein coupled receptor that regulates skin pigmentation, UV responses, and melanoma risk. It is a highly polymorphic gene, and loss of function correlates with a fair, UV-sensitive, and melanoma-prone phenotype due to defective epidermal melanization and sub-optimal DNA repair. MC1R signaling, achieved through adenylyl cyclase activation and generation of the second messenger cAMP, is hormonally controlled by the positive agonist melanocortin, the negative agonist agouti signaling protein, and the neutral antagonist β-defensin 3. Activation of cAMP signaling up-regulates melanin production and deposition in the epidermis which functions to limit UV penetration into the skin and enhances nucleotide excision repair, the genomic stability pathway responsible for clearing UV photolesions from DNA to avoid mutagenesis. Herein we review MC1R structure and function and summarize our laboratory’s findings on the molecular mechanisms by which MC1R signaling impacts nucleotide excision repair.

  2. Signature of Balancing Selection at the MC1R Gene in Kunming Dog Populations

    Science.gov (United States)

    Fan, Ruo-xi; Irwin, David M.; Tang, Shu-sheng; Peng, Jian-guo; Zhang, Ya-ping

    2013-01-01

    Coat color in dog breeds is an excellent character for revealing the power of artificial selection, as it is extremely diverse and likely the result of recent domestication. Coat color is generated by melanocytes, which synthesize pheomelanin (a red or yellow pigment) or eumelanin (a black or brown pigment) through the pigment type-switching pathway, and is regulated by three genes in dogs: MC1R (melanocortin receptor 1), CBD103 (β-defensin 103), and ASIP (agouti-signaling protein precursor). The genotypes of these three gene loci in dog breeds are associated with coat color pattern. Here, we resequenced these three gene loci in two Kunming dog populations and analyzed these sequences using population genetic approaches to identify evolutionary patterns that have occurred at these loci during the recent domestication and breeding of the Kunming dog. The analysis showed that MC1R undergoes balancing selection in both Kunming dog populations, and that the Fst value for MC1R indicates significant genetic differentiation across the two populations. In contrast, similar results were not observed for CBD103 or ASIP. These results suggest that high heterozygosity and allelic differences at the MC1R locus may explain both the mixed color coat, of yellow and black, and the difference in coat colors in both Kunming dog populations. PMID:23424634

  3. Genetic variation within coat color genes of MC1R and ASIP in Chinese brownish red Tibetan pigs.

    Science.gov (United States)

    Mao, Huirong; Ren, Jun; Ding, Nengshui; Xiao, Shijun; Huang, Lusheng

    2010-12-01

    Melanocortin receptor 1 (MC1R) and agouti signaling protein (ASIP) are two major genes affecting coat color phenotypes in mammals, and inactivation mutations in the MC1R gene are responsible for red coat color in European pig breeds. Conversely, the gain-of-function ASIP mutations block MC1R signaling and lead to the production of red pheomelanin. Chinese Tibetan pigs have three types of coat color phenotypes, including brownish red, solid black and black with patches of brownish red and white. Herein, we investigated variations of the MC1R and ASIP genes in Tibetan pigs. The results showed that the brownish red Tibet pig had the dominant black MC1R allele (E(D1)). No loss-of-function mutation in MC1R responsible for red coat color in European breeds was observed in this breed. No causal mutation for the red coat color phenotype was found in the coding sequence of the ASIP gene. A novel missense mutation c.157G > A was firstly identified in exon 2 of ASIP, which was further genotyped in 285 pigs from five Chinese breeds and three Western breeds having different coat color phenotypes. Nearly all pigs were GG homozygotes. In conclusion, no functional variant responsible for brownish red coloration was found in the coding region of MC1R and ASIP in Tibetan pigs. © 2010 The Authors. Journal compilation © 2010 Japanese Society of Animal Science.

  4. A novel role for pigment genes in the stress response in rainbow trout (Oncorhynchus mykiss)

    Science.gov (United States)

    Khan, Uniza Wahid; Øverli, Øyvind; Hinkle, Patricia M.; Pasha, Farhan Ahmad; Johansen, Ida Beitnes; Berget, Ingunn; Silva, Patricia I. M.; Kittilsen, Silje; Höglund, Erik; Omholt, Stig W.; Våge, Dag Inge

    2016-01-01

    In many vertebrate species visible melanin-based pigmentation patterns correlate with high stress- and disease-resistance, but proximate mechanisms for this trait association remain enigmatic. Here we show that a missense mutation in a classical pigmentation gene, melanocyte stimulating hormone receptor (MC1R), is strongly associated with distinct differences in steroidogenic melanocortin 2 receptor (MC2R) mRNA expression between high- (HR) and low-responsive (LR) rainbow trout (Oncorhynchus mykiss). We also show experimentally that cortisol implants increase the expression of agouti signaling protein (ASIP) mRNA in skin, likely explaining the association between HR-traits and reduced skin melanin patterning. Molecular dynamics simulations predict that melanocortin 2 receptor accessory protein (MRAP), needed for MC2R function, binds differently to the two MC1R variants. Considering that mRNA for MC2R and the MC1R variants are present in head kidney cells, we hypothesized that MC2R activity is modulated in part by different binding affinities of the MC1R variants for MRAP. Experiments in mammalian cells confirmed that trout MRAP interacts with the two trout MC1R variants and MC2R, but failed to detect regulation of MC2R signaling, possibly due to high constitutive MC1R activity. PMID:27373344

  5. Melanocortin 1 Receptor: Structure, Function, and Regulation

    Science.gov (United States)

    Wolf Horrell, Erin M.; Boulanger, Mary C.; D’Orazio, John A.

    2016-01-01

    The melanocortin 1 receptor (MC1R) is a melanocytic Gs protein coupled receptor that regulates skin pigmentation, UV responses, and melanoma risk. It is a highly polymorphic gene, and loss of function correlates with a fair, UV-sensitive, and melanoma-prone phenotype due to defective epidermal melanization and sub-optimal DNA repair. MC1R signaling, achieved through adenylyl cyclase activation and generation of the second messenger cAMP, is hormonally controlled by the positive agonist melanocortin, the negative agonist agouti signaling protein, and the neutral antagonist β-defensin 3. Activation of cAMP signaling up-regulates melanin production and deposition in the epidermis which functions to limit UV penetration into the skin and enhances nucleotide excision repair (NER), the genomic stability pathway responsible for clearing UV photolesions from DNA to avoid mutagenesis. Herein we review MC1R structure and function and summarize our laboratory’s findings on the molecular mechanisms by which MC1R signaling impacts NER. PMID:27303435

  6. Defining the Contribution of MC1R Physiological Ligands to ATR Phosphorylation at Ser435, a Predictor of DNA Repair in Melanocytes.

    Science.gov (United States)

    Jarrett, Stuart G; Wolf Horrell, Erin M; Boulanger, Mary C; D'Orazio, John A

    2015-12-01

    The melanocortin 1 receptor (MC1R), a GS-coupled receptor that signals through cAMP and protein kinase A (PKA), regulates pigmentation, adaptive tanning, and melanoma resistance. MC1R-cAMP signaling promotes PKA-mediated phosphorylation of ataxia telangiectasia and rad3-related (ATR) at Ser435 (ATR-pS435), a modification that enhances nucleotide excision repair (NER) by facilitating recruitment of the XPA protein to sites of UV-induced DNA damage. High-throughput methods were developed to quantify ATR-pS435, measure XPA-photodamage interactions, and assess NER function. We report that melanocyte-stimulating hormone (α-MSH) or ACTH induce ATR-pS435, enhance XPA's association with UV-damaged DNA and optimize melanocytic NER. In contrast, MC1R antagonists agouti signaling protein (ASIP) or human β-defensin 3 (HBD3) interfere with ATR-pS435 generation, impair the XPA-DNA interaction, and reduce DNA repair. Although ASIP and HBD3 each blocked α-MSH-mediated induction of the signaling pathway, only ASIP depleted basal ATR-pS435. Our findings confirm that ASIP diminishes agonist-independent MC1R basal signaling whereas HBD3 is a neutral MC1R antagonist that blocks activation by melanocortins. Furthermore, our data suggest that ATR-pS435 may be a useful biomarker for the DNA repair-deficient MC1R phenotype.

  7. Recurrent evolution of melanism in South American felids.

    Directory of Open Access Journals (Sweden)

    Alexsandra Schneider

    2015-02-01

    Full Text Available Morphological variation in natural populations is a genomic test bed for studying the interface between molecular evolution and population genetics, but some of the most interesting questions involve non-model organisms that lack well annotated reference genomes. Many felid species exhibit polymorphism for melanism but the relative roles played by genetic drift, natural selection, and interspecies hybridization remain uncertain. We identify mutations of Agouti signaling protein (ASIP or the Melanocortin 1 receptor (MC1R as independent causes of melanism in three closely related South American species: the pampas cat (Leopardus colocolo, the kodkod (Leopardus guigna, and Geoffroy's cat (Leopardus geoffroyi. To assess population level variation in the regions surrounding the causative mutations we apply genomic resources from the domestic cat to carry out clone-based capture and targeted resequencing of 299 kb and 251 kb segments that contain ASIP and MC1R, respectively, from 54 individuals (13-21 per species, achieving enrichment of ~500-2500-fold and ~150x coverage. Our analysis points to unique evolutionary histories for each of the three species, with a strong selective sweep in the pampas cat, a distinctive but short melanism-specific haplotype in the Geoffroy's cat, and reduced nucleotide diversity for both ancestral and melanism-bearing chromosomes in the kodkod. These results reveal an important role for natural selection in a trait of longstanding interest to ecologists, geneticists, and the lay community, and provide a platform for comparative studies of morphological variation in other natural populations.

  8. A first genotyping assay of French cattle breeds based on a new allele of the extension gene encoding the melanocortin-1 receptor (Mc1r

    Directory of Open Access Journals (Sweden)

    Julien Raymond

    2000-09-01

    Full Text Available Abstract The seven transmembrane domain melanocortin-1 receptor (Mc1r encoded by the coat color extension gene (E plays a key role in the signaling pathway of melanin synthesis. Upon the binding of agonist (melanocortin hormone, α-MSH or antagonist (Agouti protein ligands, the melanosomal synthesis of eumelanin and/or phaeomelanin pigments is stimulated or inhibited, respectively. Different alleles of the extension gene were cloned from unrelated animals belonging to French cattle breeds and sequenced. The wild type E allele was mainly present in Normande cattle, the dominant ED allele in animals with black color (i.e. Holstein, whereas the recessive e allele was identified in homozygous animals exhibiting a more or less strong red coat color (Blonde d'Aquitaine, Charolaise, Limousine and Salers. A new allele, named E1, was found in either homozygous (E1/E1 or heterozygous (E1/E individuals in Aubrac and Gasconne breeds. This allele displayed a 4 amino acid duplication (12 nucleotides located within the third cytoplasmic loop of the receptor, a region known to interact with G proteins. A first genotyping assay of the main French cattle breeds is described based on these four extension alleles.

  9. Phenotypic Characterization of LEA Rat: A New Rat Model of Nonobese Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Tadashi Okamura

    2013-01-01

    Full Text Available Animal models have provided important information for the genetics and pathophysiology of diabetes. Here we have established a novel, nonobese rat strain with spontaneous diabetes, Long-Evans Agouti (LEA rat derived from Long-Evans (LE strain. The incidence of diabetes in the males was 10% at 6 months of age and 86% at 14 months, while none of the females developed diabetes. The blood glucose level in LEA male rats was between 200 and 300 mg/dl at 120 min according to OGTT. The glucose intolerance in correspondence with the impairment of insulin secretion was observed in male rats, which was the main cause of diabetes in LEA rats. Histological examination revealed that the reduction of β-cell mass was caused by progressive fibrosis in pancreatic islets in age-dependent manner. The intracytoplasmic hyaline droplet accumulation and the disappearance of tubular epithelial cell layer associated with thickening of basement membrane were evident in renal proximal tubules. The body mass index and glycaemic response to exogenous insulin were comparable to those of control rats. The unique characteristics of LEA rat are a great advantage not only to analyze the progression of diabetes, but also to disclose the genes involved in type 2 diabetes mellitus.

  10. Scene and object vision in rats.

    Science.gov (United States)

    Simpson, E L; Gaffan, E A

    1999-02-01

    Dark Agouti rats learned to discriminate large visual displays ("scenes") in a computer-controlled Y-maze. Each scene comprised several shapes ("objects") against a contrasting background. The constant-negative paradigm was used; in each problem, one constant scene was presented on every trial together with a trial-unique variable scene, and rats were rewarded for approaching the variable scene. By varying the manner in which variables differed from the constant, we investigated what aspects of scenes and the objects comprising them were salient. In Experiment 1, rats discriminated constant scenes more easily if they contained four objects rather than six, and they showed a slight attentional bias towards the lower halves of the screens. That bias disappeared in Experiment 2. Experiments 3 and 4 showed that rats could discriminate scenes even if the objects that comprised them were closely matched in position, luminance, and area. Therefore, they encoded the form of individual objects. Rats perceived shapes of the same class (e.g. two ellipses) as more similar than shapes from different classes (e.g. ellipse and polygon) regardless of whether they also differed in area. This paradigm is suitable for studying the neuropsychology of perceiving spatial relationships in multi-object scenes and of identifying visual objects.

  11. Differentiation of hypothalamic-like neurons from human pluripotent stem cells

    Science.gov (United States)

    Wang, Liheng; Meece, Kana; Williams, Damian J.; Lo, Kinyui Alice; Zimmer, Matthew; Heinrich, Garrett; Martin Carli, Jayne; Leduc, Charles A.; Sun, Lei; Zeltser, Lori M.; Freeby, Matthew; Goland, Robin; Tsang, Stephen H.; Wardlaw, Sharon L.; Egli, Dieter; Leibel, Rudolph L.

    2015-01-01

    The hypothalamus is the central regulator of systemic energy homeostasis, and its dysfunction can result in extreme body weight alterations. Insights into the complex cellular physiology of this region are critical to the understanding of obesity pathogenesis; however, human hypothalamic cells are largely inaccessible for direct study. Here, we developed a protocol for efficient generation of hypothalamic neurons from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) obtained from patients with monogenetic forms of obesity. Combined early activation of sonic hedgehog signaling followed by timed NOTCH inhibition in human ESCs/iPSCs resulted in efficient conversion into hypothalamic NKX2.1+ precursors. Application of a NOTCH inhibitor and brain-derived neurotrophic factor (BDNF) further directed the cells into arcuate nucleus hypothalamic-like neurons that express hypothalamic neuron markers proopiomelanocortin (POMC), neuropeptide Y (NPY), agouti-related peptide (AGRP), somatostatin, and dopamine. These hypothalamic-like neurons accounted for over 90% of differentiated cells and exhibited transcriptional profiles defined by a hypothalamic-specific gene expression signature that lacked pituitary markers. Importantly, these cells displayed hypothalamic neuron characteristics, including production and secretion of neuropeptides and increased p-AKT and p-STAT3 in response to insulin and leptin. Our results suggest that these hypothalamic-like neurons have potential for further investigation of the neurophysiology of body weight regulation and evaluation of therapeutic targets for obesity. PMID:25555215

  12. Control of energy balance by hypothalamic gene circuitry involving two nuclear receptors, neuron-derived orphan receptor 1 and glucocorticoid receptor.

    Science.gov (United States)

    Kim, Sun-Gyun; Lee, Bora; Kim, Dae-Hwan; Kim, Juhee; Lee, Seunghee; Lee, Soo-Kyung; Lee, Jae W

    2013-10-01

    Nuclear receptors (NRs) regulate diverse physiological processes, including the central nervous system control of energy balance. However, the molecular mechanisms for the central actions of NRs in energy balance remain relatively poorly defined. Here we report a hypothalamic gene network involving two NRs, neuron-derived orphan receptor 1 (NOR1) and glucocorticoid receptor (GR), which directs the regulated expression of orexigenic neuropeptides agouti-related peptide (AgRP) and neuropeptide Y (NPY) in response to peripheral signals. Our results suggest that the anorexigenic signal leptin induces NOR1 expression likely via the transcription factor cyclic AMP response element-binding protein (CREB), while the orexigenic signal glucocorticoid mobilizes GR to inhibit NOR1 expression by antagonizing the action of CREB. Also, NOR1 suppresses glucocorticoid-dependent expression of AgRP and NPY. Consistently, relative to wild-type mice, NOR1-null mice showed significantly higher levels of AgRP and NPY and were less responsive to leptin in decreasing the expression of AgRP and NPY. These results identify mutual antagonism between NOR1 and GR to be a key rheostat for peripheral metabolic signals to centrally control energy balance.

  13. Teriflunomide, an inhibitor of dihydroorotate dehydrogenase for the potential oral treatment of multiple sclerosis.

    Science.gov (United States)

    Palmer, Alan M

    2010-11-01

    Teriflunomide, being developed as a potential oral treatment for multiple sclerosis (MS) by sanofi-aventis, is the active metabolite of the rheumatoid arthritis drug leflunomide. Both teriflunomide and leflunomide are inhibitors of the mitochondrial enzyme dihydroorotate dehydrogenase, which is critically involved in pyrimidine synthesis. The production of activated T-cells largely depends on de novo pyrimidine synthesis, and thus pyrimidine depletion is thought to result in the inhibition of immune cell proliferation. Therapeutic efficacy of teriflunomide has been demonstrated in vivo in an experimental autoimmune encephalomyelitis model of MS using Dark Agouti rats. In a phase II, randomized, double-blind, placebo-controlled clinical trial of patients with relapsing-remitting MS, treatment with teriflunomide reduced the number of active lesions in the brain and preliminary evidence indicated a slowing in the development of disability. Recently reported data from the phase III TEMSO clinical trial support these initial findings. Compared with current therapies, teriflunomide has the advantage of oral administration. Thus, if good efficacy is demonstrated, teriflunomide may have a role to play in the future treatment of MS.

  14. The rat pink-eyed dilution (p) mutation: an identical intragenic deletion in pink-eye dilute-coat strains and several Wistar-derived albino strains.

    Science.gov (United States)

    Kuramoto, Takashi; Gohma, Hiroshi; Kimura, Kunio; Wedekind, Dirk; Hedrich, Hans J; Serikawa, Tadao

    2005-09-01

    We identified the rat pink-eyed dilution (p) and pink eye Mishima (p(m)) mutations. The p(m) mutation, which was isolated from a wild rat caught in Mishima Japan in 1961 and is carried in the NIG-III strain, is a splice donor site mutation in intron 5. The p mutation, which was first described in 1914 and is carried in several p/p rats including the RCS and BDV strains, is an intragenic deletion including exons 17 and 18. In addition to RCS and BDV strains, several albino strains, KHR, KMI and WNA, all descendants of albino stock of the Wistar Institute, are homozygous for the p allele. Analyses revealed that the colored p strains and the Wistar-derived albino p strains had the same marker haplotype spanning approximately 4 Mb around the P locus. This indicates that these p strains share a common ancestor and the p allele did not arise independently via recurrent mutations. The historical relationship among the p strains suggests that the p deletion had been maintained in stock heterogeneous for the C and P loci and then was inherited independently by the ancestor of the Wistar albino stock and the ancestor of the pink-eyed agouti rats in Europe.

  15. Phenotypic Characterization of LEA Rat: A New Rat Model of Nonobese Type 2 Diabetes

    Science.gov (United States)

    Okamura, Tadashi; Pei, Xiang Yuan; Miyoshi, Ichiro; Shimizu, Yukiko; Takanashi-Yanobu, Rieko; Mototani, Yasumasa; Kanai, Takao; Satoh, Jo; Kimura, Noriko; Kasai, Noriyuki

    2013-01-01

    Animal models have provided important information for the genetics and pathophysiology of diabetes. Here we have established a novel, nonobese rat strain with spontaneous diabetes, Long-Evans Agouti (LEA) rat derived from Long-Evans (LE) strain. The incidence of diabetes in the males was 10% at 6 months of age and 86% at 14 months, while none of the females developed diabetes. The blood glucose level in LEA male rats was between 200 and 300 mg/dl at 120 min according to OGTT. The glucose intolerance in correspondence with the impairment of insulin secretion was observed in male rats, which was the main cause of diabetes in LEA rats. Histological examination revealed that the reduction of β-cell mass was caused by progressive fibrosis in pancreatic islets in age-dependent manner. The intracytoplasmic hyaline droplet accumulation and the disappearance of tubular epithelial cell layer associated with thickening of basement membrane were evident in renal proximal tubules. The body mass index and glycaemic response to exogenous insulin were comparable to those of control rats. The unique characteristics of LEA rat are a great advantage not only to analyze the progression of diabetes, but also to disclose the genes involved in type 2 diabetes mellitus. PMID:23691528

  16. Dynamic GABAergic afferent modulation of AgRP neurons.

    Science.gov (United States)

    Garfield, Alastair S; Shah, Bhavik P; Burgess, Christian R; Li, Monica M; Li, Chia; Steger, Jennifer S; Madara, Joseph C; Campbell, John N; Kroeger, Daniel; Scammell, Thomas E; Tannous, Bakhos A; Myers, Martin G; Andermann, Mark L; Krashes, Michael J; Lowell, Bradford B

    2016-12-01

    Agouti-related peptide (AgRP) neurons of the arcuate nucleus of the hypothalamus (ARC) promote homeostatic feeding at times of caloric insufficiency, yet they are rapidly suppressed by food-related sensory cues before ingestion. Here we identify a highly selective inhibitory afferent to AgRP neurons that serves as a neural determinant of this rapid modulation. Specifically, GABAergic projections arising from the ventral compartment of the dorsomedial nucleus of the hypothalamus (vDMH) contribute to the preconsummatory modulation of ARCAgRP neurons. In a manner reciprocal to ARCAgRP neurons, ARC-projecting leptin receptor-expressing GABAergic vDMH neurons exhibit rapid activation upon availability of food that additionally reflects the relative value of the food. Thus, leptin receptor-expressing GABAergic vDMH neurons form part of the sensory network that relays real-time information about the nature and availability of food to dynamically modulate ARCAgRP neuron activity and feeding behavior.

  17. Targeted disruption of the mouse adenine phosphoribosyltransferase (aprt) gene and the production of APRT-deficient mice

    Energy Technology Data Exchange (ETDEWEB)

    Engle, S.J.; Chen, J.; Tischfield, J.A. [Indiana Univ., School of Medicine, Indianapolis, IN (United States)] [and others

    1994-09-01

    Adenine phosphoribosyltransferase (APRT: EC 2.4.2.7), a ubiquitously expressed purine salvage enzyme, catalyzes the synthesis of AMP and inorganic pyrophosphate from existing adenine and 5-phosphoribosyl-1-pyrophosphate. Deficiency of this enzyme in humans results in the accumulation of 2,8-dihydroxyadenine leading to crystalluria and nephrolithiasis. In order to facilitate our study of this rare, autosomal recessive disorder, we applied the advances in gene targeting technology and mouse embryonic stem (ES) cell culture to the production of APRT-deficient mice. A positive-negative targeting strategy was used. The tageting vector contain 5.6 kb of the mouse APRT gene, a neomycin resistance gene in exon 3 as a positive selection marker, and a HSV thymidine kinase gene at the 3{prime} end of the homology as a negative selection marker. The vector was introduced into D3 ES cells by electroporation and the cells were selected for G418 and ganciclovir (GANC) resistance. G418-GANC resistant clones were screened by Southern blot. One of several correctly targeted clones was expanded and used for blastocyst microinjection to produce chimeric mice. Chimeric animals were bred and agouti progeny heterozygous for the targeted allele were obtained. Heterozygous animals have been bred to produce APRT-deficient animals. Matings are currently underway to determine the phenotype of APRT/HPRT-deficient animals.

  18. CST, an Herbal Formula, Exerts Anti-Obesity Effects through Brain-Gut-Adipose Tissue Axis Modulation in High-Fat Diet Fed Mice

    Directory of Open Access Journals (Sweden)

    AbuZar Ansari

    2016-11-01

    Full Text Available The brain, gut, and adipose tissue interact to control metabolic pathways, and impairment in the brain-gut-adipose axis can lead to metabolic disorders, including obesity. Chowiseungcheng-tang (CST, a herbal formulation, is frequently used to treat metabolic disorders. Here, we investigated the anti-obesity effect of CST and its link with brain-gut-adipose axis using C57BL/6J mice as a model. The animals were provided with a normal research diet (NRD or high-fat diet (HFD in absence or presence of CST or orlistat (ORL for 12 weeks. CST had a significant anti-obesity effect on a number of vital metabolic and obesity-related parameters in HFD-fed mice. CST significantly decreased the expression levels of genes encoding obesity-promoting neuropeptides (agouti-related peptide, neuropeptide Y, and increased the mRNA levels of obesity-suppressing neuropeptides (proopiomelanocortin, cocaine-and amphetamine-regulated transcript in the hypothalamus. CST also effectively decreased the expression level of gene encoding obesity-promoting adipokine (retinol-binding protein-4 and increased the mRNA level of obesity-suppressing adipokine (adiponectin in visceral adipose tissue (VAT. Additionally, CST altered the gut microbial composition in HFD groups, a phenomenon strongly associated with key metabolic parameters, neuropeptides, and adipokines. Our findings reveal that the anti-obesity impact of CST is mediated through modulation of metabolism-related neuropeptides, adipokines, and gut microbial composition.

  19. Dietary Slowly Digestible Starch Triggers the Gut-Brain Axis in Obese Rats with Accompanied Reduced Food Intake.

    Science.gov (United States)

    Hasek, Like Y; Phillips, Robert J; Zhang, Genyi; Kinzig, Kimberly P; Kim, Choon Young; Powley, Terry L; Hamaker, Bruce R

    2017-12-11

    Slowly digestible starch (SDS), as a functional carbohydrate providing a slow and sustained glucose release, may be able to modulate food intake through activation of the gut-brain axis. Diet-induced obese rats were used to test the effect on feeding behavior of high-fat (HF) diets containing an SDS, fabricated to digest into the ileum, as compared to rapidly digestible starch (RDS). Ingestion of the HF-SDS diet over an 11-week period reduced daily food intake, through smaller meal size, to the same level as a lean body control group, while the group consuming the HF-RDS diet remained at a high food intake. Expression levels (mRNA) of the hypothalamic orexigenic neuropeptide Y (NPY) and Agouti-related peptide (AgRP) were significantly reduced, and the anorexigenic corticotropin-releasing hormone (CRH) was increased, in the HF-SDS fed group compared to the HF-RDS group, and to the level of the lean control group. SDS with digestion into the ileum reduced daily food intake and paralleled suppressed expression of appetite-stimulating neuropeptide genes associated with the gut-brain axis. This novel finding suggests further exploration involving a clinical study and potential development of SDS-based functional foods as an approach to obesity control. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. CST, an Herbal Formula, Exerts Anti-Obesity Effects through Brain-Gut-Adipose Tissue Axis Modulation in High-Fat Diet Fed Mice.

    Science.gov (United States)

    Ansari, AbuZar; Bose, Shambhunath; Yadav, Mukesh Kumar; Wang, Jing-Hua; Song, Yun-Kyung; Ko, Seong-Gyu; Kim, Hojun

    2016-11-11

    The brain, gut, and adipose tissue interact to control metabolic pathways, and impairment in the brain-gut-adipose axis can lead to metabolic disorders, including obesity. Chowiseungcheng-tang (CST), a herbal formulation, is frequently used to treat metabolic disorders. Here, we investigated the anti-obesity effect of CST and its link with brain-gut-adipose axis using C57BL/6J mice as a model. The animals were provided with a normal research diet (NRD) or high-fat diet (HFD) in absence or presence of CST or orlistat (ORL) for 12 weeks. CST had a significant anti-obesity effect on a number of vital metabolic and obesity-related parameters in HFD-fed mice. CST significantly decreased the expression levels of genes encoding obesity-promoting neuropeptides (agouti-related peptide, neuropeptide Y), and increased the mRNA levels of obesity-suppressing neuropeptides (proopiomelanocortin, cocaine-and amphetamine-regulated transcript) in the hypothalamus. CST also effectively decreased the expression level of gene encoding obesity-promoting adipokine (retinol-binding protein-4) and increased the mRNA level of obesity-suppressing adipokine (adiponectin) in visceral adipose tissue (VAT). Additionally, CST altered the gut microbial composition in HFD groups, a phenomenon strongly associated with key metabolic parameters, neuropeptides, and adipokines. Our findings reveal that the anti-obesity impact of CST is mediated through modulation of metabolism-related neuropeptides, adipokines, and gut microbial composition.

  1. The neurobiology of binge-like ethanol drinking: evidence from rodent models.

    Science.gov (United States)

    Sprow, Gretchen M; Thiele, Todd E

    2012-06-06

    Binge alcohol (ethanol) drinking is a destructive pattern of ethanol consumption that may precipitate ethanol dependence-a chronic, debilitating, and prevalent health problem. While an abundance of research has focused on the neurochemical underpinnings of ethanol dependence, relatively little is known about the mechanisms underlying the heavy consumption characteristic of binge ethanol drinking. Recently, a simple preclinical model termed "drinking in the dark" (DID) was developed to examine binge-like ethanol consumption in a rodent population. This assay capitalizes on the predisposition of C57BL/6J mice to voluntarily consume substantial quantities of a high concentration (20% v/v) ethanol solution, resulting in pharmacologically relevant blood ethanol concentrations (BECs). This review provides a comprehensive overview of recent literature utilizing this model to investigate the neuromodulatory systems that may influence binge ethanol drinking. Studies examining the glutamatergic and opioidergic systems not only provide evidence for these systems in the modulation of binge-like ethanol consumption, but also suggest this preclinical model has predictive validity and may be an appropriate tool for screening novel pharmacological compounds aimed at treating binge ethanol drinking in the human population. Additionally, this review presents evidence for the involvement of the GABAergic, dopaminergic, nicotinic, and endocannabinoid systems in modulating binge-like ethanol consumption. Finally, recent evidence shows that corticotropin-releasing factor (CRF), agouti-related protein (AgRP), neuropeptide Y (NPY), and ghrelin are also implicated as impacting this pattern of ethanol consumption. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. [Folates and fetal programming: role of epigenetics and epigenomics].

    Science.gov (United States)

    Guéant, Jean-Louis; Daval, Jean-Luc; Vert, Paul; Nicolas, Jean-Pierre

    2012-12-01

    Folates are needed for synthesis of methionine, the precursor of S-adenosyl methionine (SAM). They play therefore a key role in nutrition and epigenomics by fluxing monocarbons towards synthesis or methylation of DNA and RNA, and methylation of gene transregulators, respectively. The deficiency produces intrauterine growth retardation and birth dejects. Folate deficiency deregulates epigenomic mechanisms related to fetal programming through decreased cellular availability of SAM. Epigenetic mechanisms of folate deficiency are illustrated by inheritance of coat colour of agouti mice model and altered expression of Igf2/H19 imprinting genes. Dietary exposure to fumonisin FB1 acts synergistically with folate deficiency on alterations of heterochromatin assembly. Deficiency in folate and vitamin B12 produces impaired fatty acid oxidation in liver and heart through imbalanced methylation and acetylation of PGC1-alpha and decreased expression of SIRT1, and long-lasting cognitive disabilities through impaired hippocampal cell proliferation, differentiation and plasticity and atrophy of hippocampal CA1. Deciphering these mechanisms will help understand the discordances between experimental models and population studies on folate supplementation.

  3. Central ghrelin signaling mediates the metabolic response of C57BL/6 male mice to chronic social defeat stress.

    Science.gov (United States)

    Patterson, Z R; Khazall, R; Mackay, H; Anisman, H; Abizaid, A

    2013-03-01

    Chronic stressors promote metabolic disturbances, including obesity and metabolic syndrome. Ghrelin, a peptide that promotes appetite and the accumulation of adipose tissue, is also secreted in response to stressors to protect the brain and peripheral tissues from the effects of these stressors. Here we demonstrate that elevated ghrelin levels produced by chronic exposure to social stress are associated with increased caloric intake and body weight gain in male C57BL mice. In contrast, stressed mice lacking ghrelin receptors (GHSR KO mice) or C57BL mice receiving chronic intracerebroventricular delivery of the ghrelin receptor antagonist [d-Lys(3)]-GHRP-6 show attenuated weight gain and feeding responses under the same social stress paradigm. Interestingly, stressed GHSR KO mice showed depleted sc and intrascapular brown fat depots, whereas stressed young wild-type mice did not. In old wild-type mice, chronic social defeat increased visceral and intrascapular brown fat depots in association with increases in obesity markers like hyperleptinemia and hyperinsulinemia along with increased hypothalamic expression of neuropeptide Y and Agouti related peptide. Importantly, the elevated expression of these peptides persisted least for 2 weeks after cessation of the stressor regimen. In contrast, old GHSR KO mice did not show these alterations after chronic social defeat. These results suggest that ghrelin plays an important role in the metabolic adaptations necessary to meet the energetic demands posed by stressors, but chronic exposure to stress-induced ghrelin elevations ultimately could lead to long lasting metabolic dysfunctions.

  4. Insulin Receptor Signaling in POMC, but Not AgRP, Neurons Controls Adipose Tissue Insulin Action.

    Science.gov (United States)

    Shin, Andrew C; Filatova, Nika; Lindtner, Claudia; Chi, Tiffany; Degann, Seta; Oberlin, Douglas; Buettner, Christoph

    2017-06-01

    Insulin is a key regulator of adipose tissue lipolysis, and impaired adipose tissue insulin action results in unrestrained lipolysis and lipotoxicity, which are hallmarks of the metabolic syndrome and diabetes. Insulin regulates adipose tissue metabolism through direct effects on adipocytes and through signaling in the central nervous system by dampening sympathetic outflow to the adipose tissue. Here we examined the role of insulin signaling in agouti-related protein (AgRP) and pro-opiomelanocortin (POMC) neurons in regulating hepatic and adipose tissue insulin action. Mice lacking the insulin receptor in AgRP neurons (AgRP IR KO) exhibited impaired hepatic insulin action because the ability of insulin to suppress hepatic glucose production (hGP) was reduced, but the ability of insulin to suppress lipolysis was unaltered. To the contrary, in POMC IR KO mice, insulin lowered hGP but failed to suppress adipose tissue lipolysis. High-fat diet equally worsened glucose tolerance in AgRP and POMC IR KO mice and their respective controls but increased hepatic triglyceride levels only in POMC IR KO mice, consistent with impaired lipolytic regulation resulting in fatty liver. These data suggest that although insulin signaling in AgRP neurons is important in regulating glucose metabolism, insulin signaling in POMC neurons controls adipose tissue lipolysis and prevents high-fat diet-induced hepatic steatosis. © 2017 by the American Diabetes Association.

  5. Mouse estrous cycle identification tool and images.

    Directory of Open Access Journals (Sweden)

    Shannon L Byers

    Full Text Available The efficiency of producing timed pregnant or pseudopregnant mice can be increased by identifying those in proestrus or estrus. Visual observation of the vagina is the quickest method, requires no special equipment, and is best used when only proestrus or estrus stages need to be identified. Strain to strain differences, especially in coat color can make it difficult to determine the stage of the estrous cycle accurately by visual observation. Presented here are a series of images of the vaginal opening at each stage of the estrous cycle for 3 mouse strains of different coat colors: black (C57BL/6J, agouti (CByB6F1/J and albino (BALB/cByJ. When all 4 stages (proestrus, estrus, metestrus, and diestrus need to be identified, vaginal cytology is regarded as the most accurate method. An identification tool is presented to aid the user in determining the stage of estrous when using vaginal cytology. These images and descriptions are an excellent resource for learning how to determine the stage of the estrous cycle by visual observation or vaginal cytology.

  6. The amphibian melanization inhibiting factor (MIF) blocks the alpha-MSH effect on mouse malignant melanocytes.

    Science.gov (United States)

    López-Contreras, A M; Martínez-Liarte, J H; Solano, F; Samaraweera, P; Newton, J M; Bagnara, J T

    1996-12-01

    We have found that a melanization inhibitory factor (MIF) extracted from the ventral skin of Rana forreri has a slight inhibitory effect on the activity levels of tyrosinase and dopachrome tautomerase in B16/F10 and Cloudman S-91 murine melanoma cell lines. Furthermore, this factor appears to block the effects of alpha-MSH on these enzymatic activities. However, MIF treatment does not affect the melanogenic action of theophylline on the same cells, suggesting that MIF acts proximal to MSH-mediated cAMP formation, possibly by interaction with the MSH receptor. In this way, we show that this amphibian factor has biological activity on mammalian melanocytes. This suggests the existence of mammalian counterparts of amphibian MIF in the mouse integument that might regulate epidermal melanocytes. These peptides might be related to the agouti protein, as they share similar mechanisms of action. The interaction of different peptides with the MSH receptor would be a complex but general mechanism responsible for many mammalian coat color variants.

  7. alpha-MSH activates immediate defense responses to UV-induced oxidative stress in human melanocytes.

    Science.gov (United States)

    Song, Xiuzu; Mosby, Nicole; Yang, Jennifer; Xu, Aie; Abdel-Malek, Zalfa; Kadekaro, Ana Luisa

    2009-12-01

    Exposure of cultured human melanocytes to ultraviolet radiation (UV) results in DNA damage. In melanoma, UV-signature mutations resulting from unrepaired photoproducts are rare, suggesting the possible involvement of oxidative DNA damage in melanocyte malignant transformation. Here we present data demonstrating immediate dose-dependent generation of hydrogen peroxide in UV-irradiated melanocytes, which correlated directly with a decrease in catalase activity. Pretreatment of melanocytes with alpha-melanocortin (alpha-MSH) reduced the UV-induced generation of 7,8-dihydro-8-oxyguanine (8-oxodG), a major form of oxidative DNA damage. Pretreatment with alpha-MSH also increased the protein levels of catalase and ferritin. The effect of alpha-MSH on 8-oxodG induction was mediated by activation of the melanocortin 1 receptor (MC1R), as it was absent in melanocytes expressing loss-of-function MC1R, and blocked by concomitant treatment with an analog of agouti signaling protein (ASIP), ASIP-YY. This study provides unequivocal evidence for induction of oxidative DNA damage by UV in human melanocytes and reduction of this damage by alpha-MSH. Our data unravel some mechanisms by which alpha-MSH protects melanocytes from oxidative DNA damage, which partially explain the strong association of loss-of-function MC1R with melanoma.

  8. Altered regulation of energy homeostasis in older rats in response to thyroid hormone administration.

    Science.gov (United States)

    Walrand, Stephane; Short, Kevin R; Heemstra, Lydia A; Novak, Colleen M; Levine, James A; Coenen-Schimke, Jill M; Nair, K Sreekumaran

    2014-03-01

    Hyperthyroidism causes increased energy intake and expenditure, although anorexia and higher weight loss have been reported in elderly individuals with hyperthyroidism. To determine the effect of age on energy homeostasis in response to experimental hyperthyroidism, we administered 200 μg tri-iodothyronine (T3) in 7- and 27-mo-old rats for 14 d. T3 increased energy expenditure (EE) in both the young and the old rats, although the old rats lost more weight (147 g) than the young rats (58 g) because of the discordant effect of T3 on food intake, with a 40% increase in the young rats, but a 40% decrease in the old ones. The increased food intake in the young rats corresponded with a T3-mediated increase in the appetite-regulating proteins agouti-related peptide, neuropeptide Y, and uncoupling protein 2 in the hypothalamus, but no increase occurred in the old rats. Evidence of mitochondrial biogenesis in response to T3 was similar in the soleus muscle and heart of the young and old animals, but less consistent in old plantaris muscle and liver. Despite the comparable increase in EE, T3's effect on mitochondrial function was modulated by age in a tissue-specific manner. We conclude that older rats lack compensatory mechanisms to increase caloric intake in response to a T3-induced increase in EE, demonstrating a detrimental effect of age on energy homeostasis.

  9. The effect of physical exercise on orexigenic and anorexigenic peptides and its role on long-term feeding control.

    Science.gov (United States)

    Benite-Ribeiro, Sandra Aparecida; Putt, David A; Santos, Júlia Matzenbacher

    2016-08-01

    Over the past decades, life-styles changing have led to exacerbated food and caloric intake and a reduction in energy expenditure. Obesity, main outcome of these changes, increases the risk for developing type 2 diabetes, cardiovascular disease and metabolic syndrome, the leading cause of death in adult and middle age population. Body weight and energy homeostasis are maintained via complex interactions between orexigenic and anorexigenic neuropeptides that take place predominantly in the hypothalamus. Overeating may disrupt the mechanisms of feeding control, by decreasing the expression of proopiomelanocortin (POMC) and α-melanocyte stimulating hormone (α-MSH) and increasing orexigenic neuropeptide Y (NPY) and agouti-related peptide (AgRP), which leads to a disturbance in appetite control and energy balance. Studies have shown that regular physical exercise might decrease body-weight, food intake and improve the metabolic profile, however until the currently there is no consensus about its effects on the expression of orexigenic/anorexigenic neuropeptides expression. Therefore, we propose that the type and length of physical exercise affect POMC/αMSH and NPY/AgRP systems differently and plays an important role in feeding behavior. Moreover, based on the present reports, we hypothesize that increased POMC/αMSH overcome NPY/AgRP expression decreasing food intake in long term physical exercise and that results in amelioration of several conditions related to overweight and obesity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Grape seed extract dose-responsively decreases disease severity in a rat model of mucositis; concomitantly enhancing chemotherapeutic effectiveness in colon cancer cells.

    Science.gov (United States)

    Cheah, Ker Yeaw; Howarth, Gordon Stanley; Bastian, Susan Elaine Putnam

    2014-01-01

    Mucositis is a serious disorder of the gastrointestinal tract that results from cancer chemotherapy. We investigated the effects of increasing grape seed extract doses on the severity of chemotherapy in a rat model and its coincident impact on chemotherapeutic effectiveness in colon cancer cells. Female Dark Agouti rats were gavaged with grape seed extract (400-1000 mg/kg) or water (day 3-11) and were injected intraperitoneally with 5-Fluorouracil (150 mg/kg) or saline (control) on day 9 to induce mucositis. Daily metabolic data were collected and rats were sacrificed on day 12. Intestinal tissues were collected for histological and myeloperoxidase analyses. Caco-2 cell viability was examined in response to grape seed extract in combination with 5-Fluorouracil by 3-(4,5-Dimethylthiazol-2yl)-2,5-diphenyl-tetrazolium bromide) assay. Compared with 5-Fluorouracil controls, grape seed extract (400-1000 mg/kg) significantly decreased the histological damage score (PGrape seed extract (1000 mg/kg) increased jejunal crypt depth by 25% (PGrape seed extract (600 mg/kg) decreased myeloperoxidase activity by 55% (PGrape seed extract was more effective at ameliorating 5-Fluorouracil induced intestinal injury, with effects most pronounced in the proximal jejunum. Grape seed extract (10-25 ug/mL) significantly enhanced the growth-inhibitory effects of 5-Fluorouracil by 26% (PGrape seed extract may represent a new therapeutic option to decrease the symptoms of intestinal mucositis while concurrently impacting on the viability of colon cancer cells.

  11. Glutamate and GABA as rapid effectors of hypothalamic peptidergic neurons

    Directory of Open Access Journals (Sweden)

    Cornelia eSchöne

    2012-11-01

    Full Text Available Vital hypothalamic neurons regulating hunger, wakefulness, reward-seeking, and body weight are often defined by unique expression of hypothalamus-specific neuropeptides. Gene-ablation studies show that some of these peptides, notably orexin/hypocretin (hcrt/orx, are themselves critical for stable states of consciousness and metabolic health. However, neuron-ablation studies often reveal more severe phenotypes, suggesting key roles for co-expressed transmitters. Indeed, most hypothalamic neurons, including hcrt/orx cells, contain fast transmitters glutamate and GABA, as well as several neuropeptides. What are the roles and relations between different transmitters expressed by the same neuron? Here, we consider signaling codes for releasing different transmitters in relation to transmitter and receptor diversity in behaviorally-defined, widely-projecting peptidergic neurons, such as hcrt/orx cells. We then discuss latest optogenetic studies of endogenous transmitter release from defined sets of axons in situ, which suggest that recently-characterized vital peptidergic neurons (e.g. hcrt/orx, proopiomelanocortin , and agouti-related peptide cells, as well as classical modulatory neurons (e.g. dopamine and acetylcholine cells, all use fast transmitters to control their postsynaptic targets. These optogenetic insights are complemented by recent observations of behavioral deficiencies caused by genetic ablation of fast transmission from specific neuropeptidergic and aminergic neurons. Powerful and fast (millisecond-scale GABAergic and glutamatergic signaling from neurons previously considered to be primarily modulatory raises new questions about the roles of slower co-transmitters they co-express.

  12. Perinatal stress: characteristics and effects on adult eating behavior

    Directory of Open Access Journals (Sweden)

    Matilde Cesiana da Silva

    2013-08-01

    Full Text Available Many studies have pointed out the importance of mother-child interaction in the early months of life. A few decades ago, a method called kangaroo care was developed and its main goal was to keep underweight or premature newborns in direct contact with the mother. This method has reduced the morbidity and mortality of these newborns, increasing their growth rate, breastfeeding time and mother-child contact. In rodents, the dam's presence is crucial for avoiding aggression factors that may trigger phenotypic adaptations in the pups with irreversible morphological, functional and behavioral consequences. Eating behavior is an adaptive response stemming from the external environment demand and modulated by opportunities and limitations imposed by the external environment. This behavior is regulated by a complex interaction of peripheral and central mechanisms that control hunger and satiety. The hypothalamus is a brain structure that integrates central and peripheral signals to regulate energy homeostasis and body weight. The hypothalamic nucleus have orexigenic peptides, such as neuropeptide Y and the Agouti-related peptide, and anorexigenic peptides, such as cocaine and amphetamine regulated transcript and proopiomelanocortin. An innovative study of eating behavior in experimental models of neonatal stress separates the mother from the offspring during lactation. This review describes the effects of stress during the neonatal period on general physiological factors, particularly on the control of eating behavior.

  13. Germline transmission of a novel rat embryonic stem cell line derived from transgenic rats.

    Science.gov (United States)

    Men, Hongsheng; Bauer, Beth A; Bryda, Elizabeth C

    2012-09-20

    Germline-competent rat embryonic stem (ES) cell lines are important resources for the creation of mutant rat models using ES-cell-based gene targeting technology. The ability to isolate germline-competent ES cell lines from any rat strain, including genetically modified strains, would allow for more sophisticated genetic manipulations without extensive breeding. Sprague Dawley (SD) males carrying an enhanced green fluorescent protein (EGFP) transgene were used as the founder animals for the derivation of ES cell lines. A number of ES cell lines were established and subjected to rigorous quality control testing that included assessment of pluripotency factor expression, karyotype analysis, and pathogen/sterility testing. Two male ES cell lines, SD-Tg.EC1/Rrrc and SD-Tg.EC8/Rrrc, were injected into blastocysts recovered from a cross of Dark Agouti (DA) males with SD females. Resulting chimeric animals were bred with wild-type SD mates to verify the germline transmissibility of the ES cell lines by identifying pups carrying the ES cell line-derived EGFP transgene. While both ES cell lines gave rise to chimeric animals, only SD-Tg.EC1 was germline competent. This confirms the feasibility of deriving germline-competent ES cell lines from transgenic rat strains and provides a novel ES cell line with a stable green fluorescent protein (GFP) reporter for future genetic manipulations to create new rat models.

  14. A novel role for pigment genes in the stress response in rainbow trout (Oncorhynchus mykiss)

    KAUST Repository

    Khan, Uniza Wahid

    2016-07-04

    In many vertebrate species visible melanin-based pigmentation patterns correlate with high stress- and disease-resistance, but proximate mechanisms for this trait association remain enigmatic. Here we show that a missense mutation in a classical pigmentation gene, melanocyte stimulating hormone receptor (MC1R), is strongly associated with distinct differences in steroidogenic melanocortin 2 receptor (MC2R) mRNA expression between high- (HR) and low-responsive (LR) rainbow trout (Oncorhynchus mykiss). We also show experimentally that cortisol implants increase the expression of agouti signaling protein (ASIP) mRNA in skin, likely explaining the association between HR-traits and reduced skin melanin patterning. Molecular dynamics simulations predict that melanocortin 2 receptor accessory protein (MRAP), needed for MC2R function, binds differently to the two MC1R variants. Considering that mRNA for MC2R and the MC1R variants are present in head kidney cells, we hypothesized that MC2R activity is modulated in part by different binding affinities of the MC1R variants for MRAP. Experiments in mammalian cells confirmed that trout MRAP interacts with the two trout MC1R variants and MC2R, but failed to detect regulation of MC2R signaling, possibly due to high constitutive MC1R activity.

  15. Derivation of a germline competent transgenic Fischer 344 embryonic stem cell line.

    Directory of Open Access Journals (Sweden)

    Hongsheng Men

    Full Text Available Embryonic stem (ES cell-based gene manipulation is an effective method for the generation of mutant animal models in mice and rats. Availability of germline-competent ES cell lines from inbred rat strains would allow for creation of new genetically modified models in the desired genetic background. Fischer344 (F344 males carrying an enhanced green fluorescence protein (EGFP transgene were used as the founder animals for the derivation of ES cell lines. After establishment of ES cell lines, rigorous quality control testing that included assessment of pluripotency factor expression, karyotype analysis, and pathogen/sterility testing was conducted in selected ES cell lines. One male ES cell line, F344-Tg.EC4011, was further evaluated for germline competence by injection into Dark Agouti (DA X Sprague Dawley (SD blastocysts. Resulting chimeric animals were bred with wild-type SD mates and germline transmissibility of the ES cell line was confirmed by identification of pups carrying the ES cell line-derived EGFP transgene. This is the first report of a germline competent F344 ES cell line. The availability of a new germline competent ES cell line with a stable fluorescence reporter from an inbred transgenic rat strain provides an important new resource for genetic manipulations to create new rat models.

  16. Changes in mRNA expression of arcuate nucleus appetite-regulating peptides during lactation in rats

    Science.gov (United States)

    Suzuki, Yoshihiro; Nakahara, Keiko; Maruyama, Keisuke; Okame, Rieko; Ensho, Takuya; Inoue, Yoshiyuki; Murakami, Noboru

    2014-01-01

    The contribution of hypothalamic appetite-regulating peptides to further hyperphagia accompanying the course of lactation in rats was investigated by using PCR array and real-time PCR. Furthermore, changes in the mRNA expression for appetite-regulating peptides in the hypothalamic arcuate nucleus (ARC) were analyzed at all stages of pregnancy and lactation, and also after weaning. Food intake was significantly higher during pregnancy, lactation, and after weaning than during non-lactation periods. During lactation, ARC expression of mRNAs for agouti-related protein (AgRP) and peptide YY was increased, whereas that of mRNAs for proopiomelanocortin (POMC) and cholecystokinin (CCK) was decreased, in comparison with non-lactation periods. The increase in AgRP mRNA expression during lactation was especially marked. The plasma level of leptin was significantly decreased during the course of lactation, whereas that of acyl-ghrelin was unchanged. In addition, food intake was negatively correlated with the plasma leptin level during lactation. This study has clarified synchronous changes in the expression of many appetite-regulating peptides in ARC of rats during lactation. Our results suggest that hyperphagia during lactation in rats is caused by decreases in POMC and CCK expression and increases in AgRP expression in ARC, the latter being most notable. Together with the decrease in the blood leptin level, such changes in mRNA expression may explain the further hyperphagia accompanying the course of lactation. PMID:24299740

  17. A new species of Callicebus Thomas, 1903 (Primates, Pitheciidae from the states of Mato Grosso and Pará, Brazil

    Directory of Open Access Journals (Sweden)

    Juliana Gualda-Barros

    2012-01-01

    Full Text Available A new species of titi monkey, genus Callicebus Thomas, 1903, is described based on four individuals, one from a small tributary of the left bank of Rio Teles Pires, northern state of Mato Grosso, and three others from Largo do Souza, Rio Iriri, Pará, Brazil. The new species belongs to the Callicebus moloch species group, and the main diagnostic characteristics of the new species are the whitish forehead, sideburns and beard coloration, which are contiguous, forming a frame around the blackish face; overall body pelage coloration is pale grayish-brown agouti; hands, feet and tip of the tail whitish; belly and inner sides of fore and hind limbs uniformly orange. The pattern of pelage coloration and qualitative and quantitative skull morphology are described and compared to the other species of the Callicebus moloch group. Species of the Callicebus moloch group show great similarity in skull morphology and morphometrics, making the external morphological characters, specially the chromatic fields, the most reliable diagnostic trait to identify the species.

  18. The functional requirements of mammalian hair: a compromise between crypsis and thermoregulation?

    Science.gov (United States)

    Wacker, Chris B.; McAllan, Bronwyn M.; Körtner, Gerhard; Geiser, Fritz

    2016-08-01

    Mammalian fur often shows agouti banding with a proximal dark band near the skin and a lighter distal band. We examined the function of both bands in relation to camouflage, thermal properties of pelts, and thermal energetics of dunnarts ( Sminthopsis crassicaudata), which are known to use torpor and basking. Although the distal band of dunnart fur darkened with increasing latitude, which is important for camouflage, it did not affect the thermal properties and the length of the dark band and total hair length were not correlated. In contrast, the length of the proximal dark band of preserved pelts exposed to sunlight was positively correlated ( r 2 = 0.59) with the temperature underneath the pelt ( T pelt). All dunnarts offered radiant heat basked by exposing the dark band of the hair during both rest and torpor. Basking dunnarts with longer dark bands had lower resting metabolism ( r 2 = 0.69), warmed faster from torpor ( r 2 = 0.77), required less energy to do so ( r 2 = 0.32), and reached a higher subcutaneous temperature ( T sub) at the end of rewarming ( r 2 = 0.75). We provide the first experimental evidence on the possible dual function of the color banding of mammalian fur. The distal colored band appears to be important for camouflage, whereas the length of the dark proximal hair band facilitates heat gain for energy conservation and allows animals to rewarm quickly and economically from torpor.

  19. Neuroendorine and Epigentic Mechanisms Subserving Autonomic Imbalance and HPA Dysfunction in the Metabolic Syndrome

    Science.gov (United States)

    Lemche, Erwin; Chaban, Oleg S.; Lemche, Alexandra V.

    2016-01-01

    Impact of environmental stress upon pathophysiology of the metabolic syndrome (MetS) has been substantiated by epidemiological, psychophysiological, and endocrinological studies. This review discusses recent advances in the understanding of causative roles of nutritional factors, sympathomedullo-adrenal (SMA) and hypothalamic-pituitary adrenocortical (HPA) axes, and adipose tissue chronic low-grade inflammation processes in MetS. Disturbances in the neuroendocrine systems for leptin, melanocortin, and neuropeptide Y (NPY)/agouti-related protein systems have been found resulting directly in MetS-like conditions. The review identifies candidate risk genes from factors shown critical for the functioning of each of these neuroendocrine signaling cascades. In its meta-analytic part, recent studies in epigenetic modification (histone methylation, acetylation, phosphorylation, ubiquitination) and posttranscriptional gene regulation by microRNAs are evaluated. Several studies suggest modification mechanisms of early life stress (ELS) and diet-induced obesity (DIO) programming in the hypothalamic regions with populations of POMC-expressing neurons. Epigenetic modifications were found in cortisol (here HSD11B1 expression), melanocortin, leptin, NPY, and adiponectin genes. With respect to adiposity genes, epigenetic modifications were documented for fat mass gene cluster APOA1/C3/A4/A5, and the lipolysis gene LIPE. With regard to inflammatory, immune and subcellular metabolism, PPARG, NKBF1, TNFA, TCF7C2, and those genes expressing cytochrome P450 family enzymes involved in steroidogenesis and in hepatic lipoproteins were documented for epigenetic modifications. PMID:27147943

  20. Effects of Supernatants from Escherichia coli Nissle 1917 and Faecalibacterium prausnitzii on Intestinal Epithelial Cells and a Rat Model of 5-Fluorouracil-Induced Mucositis.

    Science.gov (United States)

    Wang, Hanru; Jatmiko, Yoga D; Bastian, Susan E P; Mashtoub, Suzanne; Howarth, Gordon S

    2017-01-01

    Faecalibacterium prausnitzii (Fp) and Escherichia coli Nissle 1917 (EcN) are probiotics, which have been reported to ameliorate certain gastrointestinal disorders. We evaluated the effects of supernatants (SN) derived from Fp and EcN on 5-fluorouracil (5-FU)-treated intestinal cells and in a rat model of mucositis. In vitro: IEC-6, Caco-2, and T-84 cells were analyzed for viability and monolayer permeability. In vivo: Female dark agouti rats were gavaged with Fp or EcN SN and injected intraperitoneally with saline (control) or 5-FU to induce mucositis. Rats were euthanized and intestinal tissues collected for myeloperoxidase assay and histological analyses. In vitro: Caco-2 cell viability was further reduced when treated with Fp SN + 5-FU compared to 5-FU controls. In both Caco-2 and T-84 cells, Fp SN partially prevented the decrease in transepithelial electrical resistance (TER) caused by 5-FU administration. In vivo: 5-FU-injected rats administered Fp SN or EcN SN partly prevented body weight loss and normalized water intake compared to 5-FU controls. These results suggest a growth inhibitory mechanism of Fp SN action on transformed epithelial cells that could be mediated by effects on tight junctions. Factors derived from Fp SN and EcN SN could have a role in reducing the severity of intestinal mucositis.

  1. Effects of Streptococcus thermophilus TH-4 in a rat model of doxorubicin-induced mucositis.

    Science.gov (United States)

    Wang, Hanru; Brook, Caitlin L; Whittaker, Alexandra L; Lawrence, Andrew; Yazbeck, Roger; Howarth, Gordon S

    2013-08-01

    Mucositis is a debilitating intestinal side effect of chemotherapeutic regimens. Probiotics have been considered a possible preventative treatment for mucositis. Streptococcus thermophilus TH-4 (TH-4), a newly identified probiotic, has been shown to partially alleviate mucositis induced by administration of the antimetabolite chemotherapy drug, methotrexate in rats; likely mediated through a mechanism of folate production. However, its effects against other classes of chemotherapy drug have yet to be determined. The authors investigated the effects of TH-4 in a rat model of mucositis induced by the anthracycline chemotherapy drug, doxorubicin. Gastrointestinal damage was induced in female Dark Agouti rats (148.3 ± 1.5 g) by intraperitoneal injection of doxorubicin (20 mg/kg). Animals recieved a daily oral gavage of TH-4 at 10(9) cfu/ml or skim milk (vehicle) from days 0 to 8. At day 6, rats were injected with either saline or doxorubicin. At kill, small intestinal tissues were collected for determination of sucrase and myeloperoxidase (MPO) activities and histological assessment. Body weight was significantly decreased by doxorubicin compared with normal controls (p loss of body weight induced by doxorubicin (2.3% compared with 4%), but provided no further therapeutic benefit. The minimal amelioration of doxorubicin-induced mucositis by TH-4 further supports folate production as a likely mechanism of TH-4 action against methotrexate-induced mucositis. Further studies into TH-4 are required to confirm its applicability to other conventional chemotherapy regimens.

  2. Plasticity of the melanocortin system: determinants and possible consequences on food intake

    Directory of Open Access Journals (Sweden)

    Danaé eNuzzaci

    2015-09-01

    Full Text Available The melanocortin system is one of the most important neuronal pathways involved in the regulation of food intake and is probably the best characterized. Agouti-related peptide (AgRP and proopiomelanocortin (POMC expressing neurons located in the arcuate nucleus of the hypothalamus are key elements of this system. These two neuronal populations are sensitive to circulating molecules and receive many excitatory and inhibitory inputs from various brain areas. According to sensory and metabolic information they integrate, these neurons control different aspects of feeding behavior and orchestrate autonomic responses aimed at maintaining energy homeostasis. Interestingly, composition and abundance of pre-synaptic inputs onto arcuate AgRP and POMC neurons vary in the adult hypothalamus in response to changes in the metabolic state, a phenomenon that can be recapitulated by treatment with hormones such as leptin or ghrelin. As described in other neuroendrocrine systems, glia might be determinant to shift the synaptic configuration of AgRP and POMC neurons. Here, we discuss the physiological outcome of the synaptic plasticity of the melanocortin system, and more particularly its contribution to the control of energy balance. The discovery of this attribute has changed how we view obesity and related disorders, and opens new perspectives for their management.

  3. The hypothalamic arcuate nucleus and the control of peripheral substrates.

    Science.gov (United States)

    Joly-Amado, Aurélie; Cansell, Céline; Denis, Raphaël G P; Delbes, Anne-Sophie; Castel, Julien; Martinez, Sarah; Luquet, Serge

    2014-10-01

    The arcuate nucleus (ARC) of the hypothalamus is particularly regarded as a critical platform that integrates circulating signals of hunger and satiety reflecting energy stores and nutrient availability. Among ARC neurons, pro-opiomelanocortin (POMC) and agouti-related protein and neuropeptide Y (NPY/AgRP neurons) are considered as two opposing branches of the melanocortin signaling pathway. Integration of circulating signals of hunger and satiety results in the release of the melanocortin receptor ligand α-melanocyte-stimulating hormone (αMSH) by the POMC neurons system and decreases feeding and increases energy expenditure. The orexigenic/anabolic action of NPY/AgRP neurons is believed to rely essentially on their inhibitory input onto POMC neurons and second-orders targets. Recent updates in the field have casted a new light on the role of the ARC neurons in the coordinated regulation of peripheral organs involved in the control of nutrient storage, transformation and substrate utilization independent of food intake. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Tachykinin-1 in the central nervous system regulates adiposity in rodents.

    Science.gov (United States)

    Trivedi, Chitrang; Shan, Xiaoye; Tung, Yi-Chun Loraine; Kabra, Dhiraj; Holland, Jenna; Amburgy, Sarah; Heppner, Kristy; Kirchner, Henriette; Yeo, Giles S H; Perez-Tilve, Diego

    2015-05-01

    Ghrelin is a circulating hormone that targets the central nervous system to regulate feeding and adiposity. The best-characterized neural system that mediates the effects of ghrelin on energy balance involves the activation of neuropeptide Y/agouti-related peptide neurons, expressed exclusively in the arcuate nucleus of the hypothalamus. However, ghrelin receptors are expressed in other neuronal populations involved in the control of energy balance. We combined laser capture microdissection of several nuclei of the central nervous system expressing the ghrelin receptor (GH secretagoge receptor) with microarray gene expression analysis to identify additional neuronal systems involved in the control of central nervous system-ghrelin action. We identified tachykinin-1 (Tac1) as a gene negatively regulated by ghrelin in the hypothalamus. Furthermore, we identified neuropeptide k as the TAC1-derived peptide with more prominent activity, inducing negative energy balance when delivered directly into the brain. Conversely, loss of Tac1 expression enhances the effectiveness of ghrelin promoting fat mass gain both in male and in female mice and increases the susceptibility to diet-induced obesity in ovariectomized mice. Taken together, our data demonstrate a role TAC1 in the control energy balance by regulating the levels of adiposity in response to ghrelin administration and to changes in the status of the gonadal function.

  5. Involvement of the Blood-Brain Barrier in Metabolic Regulation.

    Science.gov (United States)

    Kastin, Abba J; Pan, Weihong

    2016-01-01

    Pertinent to pandemic obesity, the discovery of endogenous peptides that affect the ingestion of food has led to the question of how these ingestive peptides exert their actions in the brain. Whereas peripheral sources provide a ready reserve, the availability of ingestive peptides to their central nervous system targets can be regulated by the blood-brain barrier (BBB). Some of the peptides/polypeptides are transported by saturable mechanisms from blood to brain. Examples include leptin, insulin, mahogany, and pancreatic polypeptide. Some enter the brain by passive diffusion, such as neuropeptide Y, orexin A, cocaine- and amphetamine-regulated transcript, cyclo His-Pro, and amylin. Some others may have essentially no penetration of the BBB; this class includes agouti-related protein, melanin-concentrating hormone, and urocortin. The regulatory function of the BBB can be seen in various physiological states. Hyperglycemia may upregulate transport systems for leptin, urocortin, and galanin-like peptide, whereas fasting can down-regulate those for leptin and galanin-like peptide. Thus, the BBB plays a dynamic role in modulating the passage of ingestive peptides from blood to brain.

  6. The role of ghrelin signalling in second-generation antipsychotic-induced weight gain.

    Science.gov (United States)

    Zhang, Qingsheng; Deng, Chao; Huang, Xu-Feng

    2013-11-01

    Based on clinical and animal studies, this review suggests a tri-phasic effect of second-generation antipsychotics (SGAs) on circulating ghrelin levels: an initial increase exerted by the acute effect of SGAs; followed by a secondary decrease possibly due to the negative feedback from the SGA-induced body weight gain or hyperphagia; and a final re-increase to reach the new equilibrium. Moreover, the results can also vary depending on individual SGAs, other hormonal states, dietary choices, and other confounding factors including medical history, co-treatments, age, gender, and ghrelin measurement techniques. Interestingly, rats treated with olanzapine, an SGA with high weight gain liabilities, are associated with increased hypothalamic ghrelin receptor (GHS-R1a) levels. In addition, expressions of downstream ghrelin signalling parameters at the hypothalamus, including neuropeptide Y (NPY)/agouti-related peptide (AgRP) and proopiomelanocortin (POMC) are also altered under SGA treatments. Thus, understanding the role of ghrelin signalling in antipsychotic drug-induced weight gain should offer potential novel pharmacological targets for tackling the obesity side-effect of SGAs and its associated metabolic syndrome. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. C-reactive protein increases BBB permeability: implications for obesity and neuroinflammation.

    Science.gov (United States)

    Hsuchou, Hung; Kastin, Abba J; Mishra, Pramod K; Pan, Weihong

    2012-01-01

    Acute phase C-reactive protein (CRP), elevated in obesity and inflammation, is a major binding protein for leptin. It is thought that CRP contributes to leptin resistance by preventing leptin from crossing the blood-brain barrier (BBB). Here we determined how CRP interacts with the BBB and whether it deters leptin from reaching CNS targets. BBB permeability, compartmental distribution, tracer stability, and expression of tight junction protein and inflammatory marker were determined. CRP was stable in blood, but did not permeate the BBB in trace amounts. However, it increased paracellular permeability at a higher dose. Agouti viable (A(vy)) mice with adult-onset obesity show higher CRP entry into the brain. CRP did not permeate hCMEC/D3 cells nor change zona occludin-1 or cyclooxygenase-2 expression. An intermediate dose of CRP had no effect on leptin transport across the BBB after co-treatment. Thus, acute interactions between CRP and leptin at the BBB level were negligible and did not explain the leptin resistance seen in obesity. The interactions of CRP and the BBB are a two-phase process, with increased paracellular permeability at a high dose that enables its entry into the CNS and serves to induce reactive gliosis and impair CNS function. Copyright © 2012 S. Karger AG, Basel.

  8. Colorimetry provides a rapid objective measurement of de novo hair growth rate in mice.

    Science.gov (United States)

    Tzung, Tien-Yi; Yang, Chia-Yi; Huang, Yung-Chang; Kao, Fu-Jen

    2009-11-01

    Depilated mice have been used as a test platform for hair growth-regulating agents. However, currently available assessment tools for hair growth in mice are less than ideal. Tristimulus colorimetry of the fur color of depilated agouti, albino, and black mice with L*, a*, and b* values were performed daily until the full growth of pelage. Using light-emitting diode (LED) irradiation (650 and 890 nm) with a daily dose of 3.5 J/cm(2) as hair growth regulators, the hair growth rates observed by the global assessment were compared with those derived from colorimetry. In contrast to a* and b* values, L* values changed more drastically over time in the anagen phase regardless of fur color. Unlike the inhibitory effect of 650 nm irradiation, LED of 890 nm promoted de novo hair regrowth in mice. The difference in hair growth rates detected by colorimetry paralleled the observation made by the global assessment. The L* value of fur color obtained by tristimulus colorimetry was a sensitive yet quantitative indicator of de novo hair growth, and could be used to project the hair growth rate in mice.

  9. Fto colocalizes with a satiety mediator oxytocin in the brain and upregulates oxytocin gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Olszewski, Pawel K., E-mail: olsze005@umn.edu [Department of Neuroscience, Functional Pharmacology, Uppsala University, 75124 Uppsala (Sweden); Minnesota Obesity Center, Saint Paul, MN 55108 (United States); Fredriksson, Robert; Eriksson, Jenny D. [Department of Neuroscience, Functional Pharmacology, Uppsala University, 75124 Uppsala (Sweden); Mitra, Anaya [Department of Food Science and Nutrition, Saint Paul, MN 55108 (United States); Radomska, Katarzyna J. [Department of Neuroscience, Functional Pharmacology, Uppsala University, 75124 Uppsala (Sweden); Gosnell, Blake A. [Department of Food Science and Nutrition, Saint Paul, MN 55108 (United States); Solvang, Maria N. [Department of Neuroscience, Functional Pharmacology, Uppsala University, 75124 Uppsala (Sweden); Levine, Allen S. [Minnesota Obesity Center, Saint Paul, MN 55108 (United States); Department of Food Science and Nutrition, Saint Paul, MN 55108 (United States); Schioeth, Helgi B. [Department of Neuroscience, Functional Pharmacology, Uppsala University, 75124 Uppsala (Sweden)

    2011-05-13

    Highlights: {yields} The majority of neurons synthesizing a satiety mediator, oxytocin, coexpress Fto. {yields} The level of colocalization is similar in the male and female brain. {yields} Fto overexpression in hypothalamic neurons increases oxytocin mRNA levels by 50%. {yields} Oxytocin does not affect Fto expression through negative feedback mechanisms. -- Abstract: Single nucleotide polymorphisms in the fat mass and obesity-associated (FTO) gene have been associated with obesity in humans. Alterations in Fto expression in transgenic animals affect body weight, energy expenditure and food intake. Fto, a nuclear protein and proposed transcription co-factor, has been speculated to affect energy balance through a functional relationship with specific genes encoding feeding-related peptides. Herein, we employed double immunohistochemistry and showed that the majority of neurons synthesizing a satiety mediator, oxytocin, coexpress Fto in the brain of male and female mice. We then overexpressed Fto in a murine hypothalamic cell line and, using qPCR, detected a 50% increase in the level of oxytocin mRNA. Expression levels of several other feeding-related genes, including neuropeptide Y (NPY) and Agouti-related protein (AgRP), were unaffected by the FTO transfection. Addition of 10 and 100 nmol oxytocin to the cell culture medium did not affect Fto expression in hypothalamic cells. We conclude that Fto, a proposed transcription co-factor, influences expression of the gene encoding a satiety mediator, oxytocin.

  10. Efeito das atividades de ecoturismo sobre a riqueza e a abundância de espécies de mamíferos de médio e grande porte na região do Cristalino, Mato Grosso, Brasil

    Directory of Open Access Journals (Sweden)

    Ednaldo Cândido Rocha

    2012-12-01

    Full Text Available Este estudo foi desenvolvido nas Reservas Particulares do Patrimônio Natural Cristalino (670 ha e Lote Cristalino (6.539 ha e no Parque Estadual Cristalino (184.900 ha. Essas unidades de conservação são contíguas e estão localizadas no extremo centro-norte do estado do Mato Grosso, em locais considerados prioritários para a conservação, em função da alta biodiversidade e endemismos, além da elevada pressão antrópica. Desta forma, este trabalho objetivou conhecer, avaliar e comparar a estrutura das populações de mamíferos de médio e grande porte, em termos de riqueza e abundância das espécies em ambientes sem turismo e com atividades de ecoturismo na região do Cristalino. Para tanto, no período compreendido entre maio de 2008 a fevereiro de 2010 foram amostrados ambientes com floresta primária, os quais apresentavam dois níveis de perturbação antrópica: sem turismo e com atividades de ecoturismo. Os dados foram coletados utilizando a amostragem de distâncias em transecções lineares, que totalizou 468,3 Km percorridos nos períodos diurno e noturno, e registro de pegadas em parcelas previamente preparadas (n = 660 parcelas vistoriadas, além de percursos fluviais no rio Cristalino e buscas aleatórias nos locais onde não ocorriam caminhos. Registros de 37 espécies de mamíferos foram obtidos, sendo 33 de médio e grande porte e quatro de pequeno porte. Não houve diferença estatisticamente significativa na riqueza de espécies dos ambientes sem turismo e com ecoturismo, sendo que a similaridade de espécies entre eles foi alta (88%. No entanto, três táxons apresentaram abundância inferior nos ambientes com turismo: Dasyprocta leporina (Linnaeus, 1766, Mazama spp. e Dasypus kappleri Krauss, 1862. Percebe-se, portanto, que o impacto negativo das atividades de ecoturismo desenvolvidas na área de estudo foi de pequena magnitude, em termos de riqueza e abundância de mamíferos de médio e grande porte. Assim

  11. Genetic Analysis of the Cat Population of North and South of Cali, Colombia

    Directory of Open Access Journals (Sweden)

    Andrés F. PEÑA-CRUZ

    2014-05-01

    Full Text Available The coat genetic markers and skeleton abnormalities have allowed characterize the profile from more than 400 domestic cat populations around the world. 15 years ago, that profile was established in the city of Cali (Colombia. In this study it was determined if north and south of the city are subpopulations and it was compared the total profile against past study. A decrease in allele frequency of a (non-agouti and d (dilution was found, but an increase of five alleles was found, especially in l (long hair and cs (siamese. These differences could be attributed to human selection of more attractive characteristics and gene flow resulting from demographic growth city, which would also explain the first report of inhibitor and ticked abyssinian alleles. Hardy-Weinberg equilibrium was evaluated for the north, south and both areas together, using white spotting and orange loci, determining disequilibrium in orange for the three evaluated areas due to a heterozygotes deficit. North and south were divided into two, each sub-sample showed Hardy-Weinberg equilibrium, although allele frequencies and heterozygosities highlighted microgeographic structure and a relationship between founding time of the neighborhood and heterozygosity. North and south are a single population and aren´t subpopulations (FST= 0,0004, D= 0,0017, as well as nine Colombian populations with which this city was compared. It is suggested to make a microgeographical gene flow analysis and the definition of possible cat colonies in Cali.ANÁLISIS GENÉTICO DE LA POBLACIÓN DE GATOS DEL NORTE Y SUR DE CALI, COLOMBIALos marcadores genéticos del pelaje y malformaciones óseas han permitido caracterizar el perfil genético de más de 400 poblaciones del gato doméstico alrededor del mundo. Unos 15 años atrás se estableció dicho perfil en la ciudad de Cali (Colombia. En este estudio se determinó si el norte y sur de Cali se comportan como subpoblaciones y se comparó el perfil total

  12. Increased migration of antigen presenting cells to newly-formed lymphatic vessels in transplanted kidneys by glycol-split heparin.

    Directory of Open Access Journals (Sweden)

    Ditmer T Talsma

    Full Text Available Chronic renal transplant dysfunction is characterized by loss of renal function and tissue remodeling, including chronic inflammation and lymph vessel formation. Proteoglycans are known for their chemokine presenting capacity. We hypothesize that interruption of the lymphatic chemokine-proteoglycan interaction interferes with the lymphatic outflow of leukocytes from the renal graft and might decrease the anti-graft allo-immune response.In a rat renal chronic transplant dysfunction model (female Dark-Agouti to male Wistar Furth, chemokines were profiled by qRT-PCR in microdissected tubulo-interstitial tissue. Disruption of lymphatic chemokine-proteoglycan interaction was studied by (non-anticoagulant heparin-derived polysaccharides in vitro and in renal allografts. The renal allograft function was assessed by rise in plasma creatinine and urea.Within newly-formed lymph vessels of transplanted kidneys, numerous CD45+ leukocytes were found, mainly MHCII+, ED-1-, IDO-, HIS14-, CD103- antigen presenting cells, most likely representing a subset of dendritic cells. Treatment of transplanted rats with regular heparin and two different (non-anticoagulant heparin derivatives revealed worsening of kidney function only in the glycol-split heparin treated group despite a two-fold reduction of tubulo-interstitial leukocytes (p<0.02. Quantitative digital image analysis however revealed increased numbers of intra-lymphatic antigen-presenting cells only in the glycol-split heparin group (p<0.01. The number of intra-lymphatic leukocytes significantly correlates with plasma creatinine and urea, and inversely with creatinine clearance.Treatment of transplanted rats with glycol-split heparin significantly increases the number of intra-lymphatic antigen presenting cells, by increased renal diffusion of lymphatic chemokines, thereby increasing the activation and recruitment of antigen presenting cells towards the lymph vessel. This effect is unwanted in the

  13. Further characterization of diabetes mellitus and body weight loss in males of the congenic mouse strain DDD.Cg-A(y.).

    Science.gov (United States)

    Suto, Jun-ichi; Satou, Kunio

    2015-02-01

    The A(y) allele at the agouti locus causes obesity and promotes linear growth in mice. However, body weight gain stops between 16 and 17 weeks after birth, and then, body weight decreases gradually in DDD.Cg-A(y) male mice. Body weight loss is a consequence of diabetes mellitus, which is genetically controlled mainly by a quantitative trait locus (QTL) on chromosome 4. This study aimed to further characterize diabetes mellitus and body weight loss in DDD.Cg-A(y) males. The number of β-cells was markedly reduced, and plasma insulin levels were very low in the DDD.Cg-A(y) males. Using a backcross progeny of DDD × (B6 × DDD.Cg-A(y)) F1-A(y), we identified one significant QTL for plasma insulin levels on distal chromosome 4, which was coincidental with QTL for hyperglycemia and lower body weight. The DDD allele was associated with decreased plasma insulin levels. When the DDD.Cg-A(y) males were housed under three different housing conditions [group housing (4 or 5 DDD.Cg-A(y) and DDD males), individual housing (single DDD.Cg-A(y) male) and single male housing with females (single DDD.Cg-A(y) male with DDD.Cg-A(y) or DDD females)], diabetes mellitus and body weight loss were most severely expressed in individually housed mice. Thus, the severity of diabetes and body weight loss in the DDD.Cg-A(y) males was strongly influenced by the housing conditions. These results demonstrate that both genetic and nongenetic environmental factors are involved in the development of diabetes mellitus and body weight loss in the DDD.Cg-A(y) males.

  14. Differential effect of prolonged food restriction and fasting on hypothalamic malonyl-CoA concentration and expression of orexigenic and anorexigenic neuropeptides genes in rats.

    Science.gov (United States)

    Sucajtys-Szulc, Elzbieta; Turyn, Jacek; Goyke, Elzbieta; Korczynska, Justyna; Stelmanska, Ewa; Slominska, Ewa; Smolenski, Ryszard T; Rutkowski, Boleslaw; Swierczynski, Julian

    2010-02-01

    Several lines of evidence suggest that malonyl-CoA in the hypothalamus plays an important role in monitoring and modulating body energy balance. In fasted state the level of malonyl-CoA concentration significantly decreases. Simultaneously, orexigenic neuropeptides (NPY - neuropeptide Y, AgRP - agouti-related peptide) genes are expressed at high level, whereas anorexigenic neuropeptides (CART - cocaine-and amphetamine-regulated transcript, POMC - proopiomelanocortin) genes are expressed at low level. When food intake resumes, opposite effect is observed. This study examined the effect of prolonged food restriction, common in humans trying to lose body weight on expression of orexigenic and anorexigenic neuropeptides genes and on malonyl-CoA content in rat whole hypothalamus. We observed an increase of NPY and AgRP mRNA levels in hypothalamus of rats kept on 30 days-long food restriction (50% of the amount of food consumed by controls). Simultaneously, a decrease of CART and POMC mRNA levels occurred. Refeeding caused a decrease in NPY and POMC mRNA levels without effect on AgRP and CART mRNA. Surprisingly, both prolonged food restriction and food restriction/refeeding caused the increase of malonyl-CoA level in whole hypothalamus. In contrast, fasting for 24h caused the decrease of malonyl-CoA level, which was associated with the up-regulation of NPY and AgRP genes expression and down-regulation of CART and POMC genes expression. After refeeding opposite effect was observed. These results indicate that prolonged food restriction and acute fasting, conditions in which energy expenditure exceeds intake, differentially affect malonyl-CoA concentration and similarly affect orexigenic and anorexigenic neuropeptide genes expression in whole rat hypothalamus. (c) 2009 Elsevier Ltd. All rights reserved.

  15. Prenatal nutrition and the risk of adult obesity: Long-term effects of nutrition on epigenetic mechanisms regulating gene expression.

    Science.gov (United States)

    Navarro, Estanislau; Funtikova, Anna N; Fíto, Montserrat; Schröder, Helmut

    2017-01-01

    Solid epidemiological evidence indicates that part of the risk of obesity in adulthood could be programmed during prenatal development by the quality of maternal nutrition. Nevertheless, the molecular mechanisms involved are mostly unknown, which hinders our capacity to develop effective intervention policies. Here, we discuss the hypothesis that mechanisms underlying prenatal programming of adult risk are epigenetic and sensitive to environmental cues such as nutrition. While the information encoded in DNA is essentially stable, regulatory epigenetic mechanisms include reversible, covalent modifications of DNA and chromatin, such as methylation, acetylation etc. It is known that dietary availability of methyl donors has an impact on the patterns of gene expression by affecting DNA methylation at regulatory regions, a likely basis for reprogramming developmental plasticity. The Agouti and Axin-fused genes, as well as the embryonic growth factor IGF2/H19 locus are examples of diet-induced modulation of phenotypic traits by affecting methylation of gene-regulatory regions. Recent work has evidenced an unsuspected role for chromatin as metabolic sensor. Chromatin is susceptible to a number of post-translational modifications that modulate gene expression, among them the GlcNAcylation of histone proteins and other epigenetic regulators. Intracellular levels of the precursor molecule UDP-GlcNAc, and hence the degree of global chromatin GlcNAcylation, depend on the energetic state of the cell, making GlcNAcylation a functional link between nutrition and regulation of gene expression. Dietary interference with these regulatory mechanisms could effectively counteract the early-life programming of adult risk. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Seasonal Differences in Relative Gene Expression of Putative Central Appetite Regulators in Arctic Charr (Salvelinus alpinus Do Not Reflect Its Annual Feeding Cycle.

    Directory of Open Access Journals (Sweden)

    Anja Striberny

    Full Text Available The highly seasonal anadromous Arctic charr (Salvelinus alpinus was used to investigate the possible involvement of altered gene expression of brain neuropeptides in seasonal appetite regulation. Pro-opiomelanocortin (POMCA1, POMCA2, Cocaine and amphetamine regulated transcript (CART, Agouti related Peptide (AgRP, Neuropeptide Y (NPY and Melanocortin Receptor 4 (MC4-R genes were examined. The function of centrally expressed Leptin (Lep in fish remains unclear, so Lep (LepA1, LepA2 and Leptin Receptor (LepR genes were included in the investigation. In a ten months study gene expression was analysed in hypothalamus, mesencephalon and telencephalon of immature charr held under natural photoperiod (69°38'N and ambient temperature and given excess feed. From April to the beginning of June the charr did not feed and lost weight, during July and August they were feeding and had a marked increase in weight and condition factor, and from November until the end of the study the charr lost appetite and decreased in weight and condition factor. Brain compartments were sampled from non-feeding charr (May, feeding charr (July, and non-feeding charr (January. Reverse transcription real-time quantitative PCR revealed temporal patterns of gene expression that differed across brain compartments. The non-feeding charr (May, January had a lower expression of the anorexigenic LepA1, MC4-R and LepR in hypothalamus and a higher expression of the orexigenic NPY and AgRP in mesencephalon, than the feeding charr (July. In the telencephalon, LepR was more highly expressed in January and May than in July. These results do not indicate that changes in central gene expression of the neuropeptides investigated here directly induce seasonal changes in feeding in Arctic charr.

  17. Prey preferences of the jaguar Panthera onca reflect the post-Pleistocene demise of large prey.

    Directory of Open Access Journals (Sweden)

    Matt W Hayward

    2016-01-01

    Full Text Available Documenting the impacts of the Pleistocene megafaunal extinctions on predator-prey interactions is a challenge because of the incomplete fossil record and depauperate extant community structure. We used a comparative ecological approach to investigate whether the existing prey preference patterns of jaguars Panthera onca were potentially affected by the Pleistocene extinctions in the Americas compared with large felids in Africa and Asia. We reviewed the literature and found 25 studies reporting 3214 jaguar kills recorded throughout the species’ distribution. We found that jaguars significantly preferred capybara Hydrochaeris hydrochaeris and giant anteater Myrmecophaga tridactyla, and avoided agoutis, carnivorans, primates, black-eared opossum Didelphis marsupialis and tapirs. Generalised linear models showed that jaguars select prey primarily based on socio-ecological and behavioural traits (abundance and herd size, rather than morphological characteristics (body size. Nonetheless, their accessible prey weight range was 6-60 kg, preferred prey weight range was 45-85 kg, and mean mass of significantly preferred prey was 32 ± 13 kg leading to a predator to prey body mass ratio of 1:0.53, which is much less than that of other solitary felids. Compared with other large, solitary felids, jaguars have an unusual predator to prey body mass ratio, show limited effect of prey morphology as a driver of prey selection, lack evidence of optimal foraging beyond their preferred prey, and an absence of preferentially hunting on Cetartiodactyla herbivores. These features, coupled with the reduction in jaguar body mass since the Pleistocene, suggest that the loss of larger potential prey items within the preferred and accessible weight ranges at the end-Pleistocene still affects jaguar predatory behaviour. It may be that jaguars survived this mass extinction event by preferentially preying on relatively small species.

  18. Perinatal Lead Exposure Alters Gut Microbiota Composition and Results in Sex-specific Bodyweight Increases in Adult Mice.

    Science.gov (United States)

    Wu, Jianfeng; Wen, Xiaoquan William; Faulk, Christopher; Boehnke, Kevin; Zhang, Huapeng; Dolinoy, Dana C; Xi, Chuanwu

    2016-06-01

    Heavy metal pollution is a principle source of environmental contamination. Epidemiological and animal data suggest that early life lead (Pb) exposure results in critical effects on epigenetic gene regulation and child and adult weight trajectories. Using a mouse model of human-relevant exposure, we investigated the effects of perinatal Pb exposure on gut microbiota in adult mice, and the link between gut microbiota and bodyweight changes. Following Pb exposure during gestation and lactation via maternal drinking water, bodyweight in A(vy) strain wild-type non-agouti (a/a) offspring was tracked through adulthood. Gut microbiota of adult mice were characterized by deep DNA sequencing of bacterial 16S ribosomal RNA genes. Data analyses were stratified by sex and adjusted for litter effects. A Bayesian variable selection algorithm was used to analyze associations between bacterial operational taxonomic units and offspring adult bodyweight. Perinatal Pb exposure was associated with increased adult bodyweight in male (P compositions were significantly different (analysis of molecular variance, P gut microbiota were highly associated with adult bodyweight (P = .028; effect size = 2.59). Thus, perinatal Pb exposure results in altered adult gut microbiota regardless of sex, and these changes are highly correlated with increased bodyweight in males. Adult gut microbiota can be shaped by early exposures and may contribute to disease risks in a sex-specific manner. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  19. Cloning and characterization of the 5'-flanking region of the pig AgRP gene.

    Science.gov (United States)

    Ling, Fei; Wang, Tao; Wei, Liqiong; Zhu, Xiaoping; Chen, Yaosheng; Li, Jiaqi; Zhang, Zongwu; Du, Hongli; Wang, Xiaoning; Wang, Jufang

    2011-04-01

    Agouti-related peptide (AgRP), a brain neuropeptide generated by AgRP/neuropeptide Y (NPY) neurons, plays a vital role in the hypothalamic regulation of energy homeostasis. RT-PCR and real-time PCR were carried out in various tissues to detect the AgRP expression pattern in pigs. Our RT-PCR results showed that the pig AgRP gene was ubiquitously expressed in all examined tissues including heart, liver, spleen, lung, kidney, stomach, bladder, m. longissimus, belly fat, brain, large intestine, lymph, back fat, skin, and hypothalamus. Real-time quantitative PCR experiments revealed that it is in the hypothalamus with the highest expression of AgRP both in adult Lantang and Landrace pigs compared to the back fat and m.longissimus muscle and the cDNA level of AgRP in the hypothalamus of adult Chinese indigenous Lantang pig (fat-type) is significantly higher than that of Landrace pig (lean-type). To understand the regulation of the pig AgRP gene, the 5'-flanking region was isolated from a pig bacterial artificial chromosome library and used in a luciferase reporter assay. A positive cis-acting element for efficient AgRP expression was identified at nucleotides -501 to -479, by 5'-serial deletion of the promoter. Electrophoretic mobility-shift assays (EMSA) with competing oligonucleotides revealed that the critical region contained a cis-acting element for Neurogenic Differentiation (NeuroD), which is a member of the NeuroD family of basic-helix-loop-helix transcription factors. This element has not been reported in human or mouse AgRP genes. Our results indicated that NeuroD might be an essential regulatory factor for transcription of pig AgRP, providing an important clue about energy homeostasis regulation in the porcine and human brain.

  20. Eating behavior in frontotemporal dementia: Peripheral hormones vs hypothalamic pathology.

    Science.gov (United States)

    Ahmed, Rebekah M; Latheef, Sahar; Bartley, Lauren; Irish, Muireann; Halliday, Glenda M; Kiernan, Matthew C; Hodges, John R; Piguet, Olivier

    2015-10-13

    To contrast the relationships of hormonal eating peptides and hypothalamic volumes to eating behavior and metabolic changes (body mass index [BMI]) in behavioral variant frontotemporal dementia (bvFTD) and semantic variant primary progressive aphasia (svPPA). Seventy-five patients with dementia (19 bvFTD, 26 svPPA, and 30 Alzheimer disease dementia) and 23 controls underwent fasting blood analyses of leptin, ghrelin, cholecystokinin, peptide tyrosine tyrosine (PYY), and agouti-related peptide (AgRP) levels. On brain MRI anterior, posterior, and total hypothalamic volumes were measured. Relationships between endocrine measures, hypothalamic volumes, eating behaviors, and BMI were investigated. Levels of AgRP were higher in patients with bvFTD (69 ± 89 pg/mL) and svPPA (62 ± 81 pg/mL) compared with controls (23 ± 19 pg/mL, p < 0.01). No differences were found for leptin, oxytocin, cholecystokinin, ghrelin, and PYY levels. Patients with bvFTD and svPPA had higher scores on questionnaires measuring eating behaviors. Atrophy of the posterior and total hypothalamus was observed in the bvFTD group only. Linear regression modeling revealed that leptin and AgRP levels predicted BMI. Eating abnormalities are multifactorial in FTD. In bvFTD, they are in part related to hypothalamic degeneration, with potential disintegration of the network connections between the hypothalamus and orbitofrontal cortex/reward pathways. In svPPA, although hypothalamic volumes are preserved, this group experiences elevated AgRP levels similar to bvFTD, which predicts BMI in both groups. This finding highlights the potential key role of AgRP in eating and metabolic changes and provides a potential target for treatment to modify disease progression. © 2015 American Academy of Neurology.

  1. Early-life lead exposure results in dose- and sex-specific effects on weight and epigenetic gene regulation in weanling mice.

    Science.gov (United States)

    Faulk, Christopher; Barks, Amanda; Liu, Kevin; Goodrich, Jaclyn M; Dolinoy, Dana C

    2013-01-01

    Epidemiological and animal data suggest that the development of adult chronic conditions is influenced by early-life exposure-induced changes to the epigenome. This study investigates the effects of perinatal lead (Pb) exposure on DNA methylation and bodyweight in weanling mice. Viable yellow agouti (A(vy)) mouse dams were exposed to 0, 2.1, 16 and 32 ppm Pb acetate before conception through weaning. Epigenetic effects were evaluated by scoring coat color of A(vy)/a offspring and quantitative bisulfite sequencing of two retrotransposon-driven (A(vy) and CDK5 activator-binding protein intracisternal A particle element) and two imprinted (Igf2 and Igf2r) loci in tail DNA. Maternal blood Pb levels were below the limit of detection in controls, and 4.1, 25.1 and 32.1 µg/dl for each dose, respectively. Pb exposure was associated with a trend of increased wean bodyweight in males (p = 0.03) and altered coat color in A(vy)/a offspring. DNA methylation at A(vy) and the CDK5 activator-binding protein intracisternal A-particle element was significantly different from controls following a cubic trend (p = 0.04; p = 0.01), with male-specific effects at the A(vy) locus. Imprinted genes did not shift in methylation across exposures. Dose- and sex-specific responses in bodyweight and DNA methylation indicate that Pb acts on the epigenome in a locus-specific fashion, dependent on the genomic feature hosting the CpG site of interest, and that sex is a factor in epigenetic response.

  2. Role of Mitochondrial Dysfunction in Hypertension and Obesity.

    Science.gov (United States)

    Lahera, Vicente; de Las Heras, Natalia; López-Farré, Antonio; Manucha, Walter; Ferder, León

    2017-02-01

    Mitochondria are essential for the maintenance of normal physiological function of tissue cells. Mitochondria are subject to dynamic processes in order to establish a control system related to survival or cell death and adaptation to changes in the metabolic environment of cells. Mitochondrial dynamics includes fusion and fission processes, biogenesis, and mitophagy. Modifications of mitochondrial dynamics in organs involved in energy metabolism such as the pancreas, liver, skeletal muscle, and white adipose tissue could be of relevance for the development of insulin resistance, obesity, and type 2 diabetes. Mitochondrial dynamics and the factors involved in its regulation are also critical for neuronal development, survival, and function. Modifications in mitochondrial dynamics in either agouti-related peptide (AgRP) or pro-opiomelanocortin (POMC), circuits which regulates feeding behavior, are related to changes of food intake, energy balance, and obesity development. Activation of the sympathetic nervous system has been considered as a crucial point in the pathogenesis of hypertension among obese individuals and it also plays a key role in cardiac remodeling. Hypertension-related cardiac hypertrophy is associated with changes in metabolic substrate utilization, dysfunction of the electron transport chain, and ATP synthesis. Alterations in both mitochondrial dynamics and ROS production have been associated with endothelial dysfunction, development of hypertension, and cardiac hypertrophy. Finally, it might be postulated that alterations of mitochondrial dynamics in white adipose tissue could contribute to the development and maintenance of hypertension in obesity situations through leptin overproduction. Leptin, together with insulin, will induce activation of sympathetic nervous system with consequences at renal, vascular, and cardiac levels, driving to sodium retention, hypertension, and left ventricular hypertrophy. Moreover, both leptin and insulin will

  3. Bone marrow fat has brown adipose tissue characteristics, which are attenuated with aging and diabetes.

    Science.gov (United States)

    Krings, A; Rahman, S; Huang, S; Lu, Y; Czernik, P J; Lecka-Czernik, B

    2012-02-01

    Fat occupies a significant portion of bone cavity however its function is largely unknown. Marrow fat expands during aging and in conditions which affect energy metabolism, indicating that fat in bone is under similar regulatory mechanisms as other fat depots. On the other hand, its location may determine specific functions in the maintenance of the environment for bone remodeling and hematopoiesis. We have demonstrated that marrow fat has a distinctive phenotype, which resembles both, white and brown adipose tissue (WAT and BAT, respectively). Marrow adipocytes express gene markers of brown adipocytes at levels characteristic for the BAT, including transcription factor Prdm16, and regulators of thermogenesis such as deiodinase 2 (Dio2) and PGC1α. The levels of expression of BAT-specific gene markers are decreased in bone of 24 mo old C57BL/6 and in diabetic yellow agouti A(vy)/a mice implicating functional changes of marrow fat occurring with aging and diabetes. Administration of antidiabetic TZD rosiglitazone, which sensitizes cells to insulin and increases adipocyte metabolic functions, significantly increased both, BAT (UCP1, PGC1α, Dio2, β3AR, Prdm16, and FoxC2) and WAT (adiponectin and leptin) gene expression in marrow of normoglycemic C57BL/6 mice, but failed to increase the expression of BAT, but not WAT, gene markers in diabetic mice. In conclusion, the metabolic phenotype of marrow fat combines both BAT and WAT characteristics. Decrease in BAT-like characteristics with aging and diabetes may contribute to the negative changes in the marrow environment supporting bone remodeling and hematopoiesis. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Central melanocortins regulate the motivation for sucrose reward.

    Science.gov (United States)

    Pandit, Rahul; van der Zwaal, Esther M; Luijendijk, Mieneke C M; Brans, Maike A D; van Rozen, Andrea J; Oude Ophuis, Ralph J A; Vanderschuren, Louk J M J; Adan, Roger A H; la Fleur, Susanne E

    2015-01-01

    The role of the melanocortin (MC) system in feeding behavior is well established. Food intake is potently suppressed by central infusion of the MC 3/4 receptor agonist α-melanocyte stimulating hormone (α-MSH), whereas the MC 3/4 receptor inverse-agonist Agouti Related Peptide (AGRP) has the opposite effect. MC receptors are widely expressed in both hypothalamic and extra-hypothalamic brain regions, including nuclei involved in food reward and motivation, such as the nucleus accumbens (NAc) and the ventral tegmental area. This suggests that MCs modulate motivational aspects of food intake. To test this hypothesis, rats were injected intracerebroventricularly with α-MSH or AGRP and their motivation for sucrose was tested under a progressive ratio schedule of reinforcement. Food motivated behavior was dose-dependently decreased by α-MSH. Conversely, AGRP increased responding for sucrose, an effect that was blocked by pretreatment with the dopamine receptor antagonist α-flupenthixol. In contrast to progressive ratio responding, free intake of sucrose remained unaltered upon α-MSH or AGRP infusion. In addition, we investigated whether the effects of α-MSH and AGRP on food motivation were mediated by the NAc shell. In situ hybridization of MC3 and MC4 receptor expression confirmed that the MC4 receptor was expressed throughout the NAc, and injection of α-MSH and AGRP into the NAc shell caused a decrease and an increase in motivation for sucrose, respectively. These data show that the motivation for palatable food is modulated by MC4 receptors in the NAc shell, and demonstrate cross-talk between the MC and dopamine system in the modulation of food motivation.

  5. Sodium tungstate regulates food intake and body weight through activation of the hypothalamic leptin pathway.

    Science.gov (United States)

    Amigó-Correig, M; Barceló-Batllori, S; Piquer, S; Soty, M; Pujadas, G; Gasa, R; Bortolozzi, A; Carmona, M C; Gomis, R

    2011-03-01

    Sodium tungstate is an anti-obesity drug targeting peripheral tissues. In vivo, sodium tungstate reduces body weight gain and food intake through increasing energy expenditure and lipid oxidation, but it also modulates hypothalamic gene expression when orally administered, raising the possibility of a direct effect of sodium tungstate on the central nervous system. Sodium tungstate was administered intraperitoneally (ip) to Wistar rats, and its levels were measured in cerebrospinal fluid through mass spectrometry. Body weight gain and food intake were monitored for 24 h after its administration in the third ventricle. Hypothalamic protein was obtained and subjected to western blot. In vitro, hypothalamic N29/4 cells were treated with 100 µM sodium tungstate or 1 nM leptin, and protein and neural gene expression were analysed. Sodium tungstate crossed the blood-brain barrier, reaching a concentration of 1.31 ± 0.07 mg/l in cerebrospinal fluid 30 min after ip injection. When centrally administered, sodium tungstate decreased body weight gain and food intake and increased the phosphorylation state of the main kinases and proteins involved in leptin signalling. In vitro, sodium tungstate increased the phosphorylation of janus kinase-2 (JAK2) and extracellular signal-regulated kinase-1/2 (ERK1/2), but the activation of each kinase did not depend on each other. It regulated c-myc gene expression through the JAK2/STAT system and c-fos and AgRP (agouti-related peptide) gene expression through the ERK1/2 pathway simultaneously and independently. Sodium tungstate increased the activity of several kinases involved in the leptin signalling system in an independent way, making it a suitable and promising candidate as a leptin-mimetic compound in order to manage obesity. © 2011 Blackwell Publishing Ltd.

  6. Quantitative trait loci that control body weight and obesity in an F2 intercross between C57BL/6J and DDD.Cg-Ay mice.

    Science.gov (United States)

    Suto, Jun-ichi

    2011-07-01

    I have developed a congenic mouse strain for the A(y) allele at the agouti locus in an inbred DDD/Sgn strain, DDD.Cg-A(y). DDD.Cg-A(y) females are extremely obese and significantly heavier than B6.Cg-A(y) females. The objectives of this study were to determine the genetic basis of obesity in DDD.Cg-A(y) mice, and to determine whether or not their high body weight was due to the presence of DDD background-specific modifiers. I performed quantitative trait locus (QTL) analyses for body weight and body mass index in two types of F(2) mice [F2 A(y) (F(2) mice carrying the A(y) allele) and F(2) non-A(y) (F2 mice without the A(y) allele)] produced by crossing C57BL/6J females and DDD.Cg-A(y) males. The results of the QTL analysis of F(2) A(y) mice were very similar to those obtained for F(2) non-A(y) mice. It was unlikely that the high body weight of DDD.Cg-A(y) mice was due to the presence of specific modifiers. When both F(2) datasets were merged and analyzed, four significant body weight QTLs were identified on chromosomes 6, 9, and 17 (2 loci) and four significant obesity QTLs were identified on chromosomes 1, 6, 9, and 17. Although the presence of DDD background-specific modifiers was not confirmed, a multifactorial basis of obesity in DDD.Cg-A(y) females was thus revealed.

  7. Impact of hypothalamic reactive oxygen species in the control of energy metabolism and food intake

    Directory of Open Access Journals (Sweden)

    Anne eDrougard

    2015-02-01

    Full Text Available Hypothalamus is a key area involved in the control of metabolism and food intake via the integrations of numerous signals (hormones, neurotransmitters, metabolites from various origins. These factors modify hypothalamic neurons activity and generate adequate molecular and behavioral responses to control energy balance. In this complex integrative system, a new concept has been developed in recent years, that includes reactive oxygen species (ROS as a critical player in energy balance. ROS are known to act in many signaling pathways in different peripheral organs, but also in hypothalamus where they regulate food intake and metabolism by acting on different types of neurons, including proopiomelanocortin (POMC and agouti-related protein (AgRP/neuropeptide Y (NPY neurons. Hypothalamic ROS release is under the influence of different factors such as pancreatic and gut hormones, adipokines (leptin, apelin,..., neurotransmitters and nutrients (glucose, lipids,.... The sources of ROS production are multiple including NADPH oxidase, but also the mitochondria which is considered as the main ROS producer in the brain. ROS are considered as signaling molecules, but conversely impairment of this neuronal signaling ROS pathway contributes to alterations of autonomic nervous system and neuroendocrine function, leading to metabolic diseases such as obesity and type 2 diabetes.In this review we focus our attention on factors that are able to modulate hypothalamic ROS release in order to control food intake and energy metabolism, and whose deregulations could participate to the development of pathological conditions. This novel insight reveals an original mechanism in the hypothalamus that controls energy balance and identify hypothalamic ROS signaling as a potential therapeutic strategy to treat metabolic disorders.

  8. An N-(alkylcarbonyl)anthranilic acid derivative prolongs cardiac allograft survival synergistically with cyclosporine A in a high-responder rat model.

    Science.gov (United States)

    Chen, Jibing; Xia, Junjie; Axelsson, Bengt; Fritzson, Ingela; Ekberg, Henrik; Törngren, Marie; Qi, Zhongquan

    2010-08-01

    We investigated the immunosuppressive effects of the dihydroortate dehydrogenase (DHODH) inhibitor compounds ABR-222417 and ABR-224050 from Active Biotech (Sweden). We verified the inhibitory effects of these compounds on the proliferation of CD4(+) and CD8(+) T-cells in vivo by using superantigen staphylococcus enterotoxin A (SEA)-mediated proliferation test. To evaluate their efficacy, the compounds were screened in a low-responder heart allograft transplantation model in rats [heart from Piebald Virol Glaxo (PVG) transplanted to Dark Agouti (DA)]. The immunosuppressive effects of the compounds were then investigated in a high-responder model (DA to PVG). Treatment with ABR-222417 (30 mg/kg) was more efficient than that with ABR-224050 (10 mg/kg), and the former provided a longer graft median survival time (MST, 29.5 days) than the latter (MST, 18.5 days). Furthermore, there was a marked increase in graft survival time (53 days) when low doses of ABR-222417 and cyclosporine A (CsA) were used in combination. No sign of tolerability problems was detected using this combination or when ABR-222417 was used singly at a higher dose. Furthermore, T-cell proliferation studies in vitro support that the anti proliferative effect of ABR-222417 is caused by inhibition of de novo pyrimidine synthesis, which is the consequence of DHODH inhibition. These results show that ABR-222417 had marked immunosuppressive effects on the heart allograft transplantation and that it exerts an even more powerful inhibitory effect on graft rejection when used in combination with CsA, with good tolerability. Copyright © 2010 Elsevier B.V. All rights reserved.

  9. The effects of exercise on hypothalamic neurodegeneration of Alzheimer's disease mouse model.

    Directory of Open Access Journals (Sweden)

    Khoa Do

    Full Text Available Alzheimer's disease is a neurodegenerative disorder that affects the central nervous system. In this study, we characterized and examined the early metabolic changes in the triple transgenic mouse AD model (3xtg-AD, and their relationship with the hypothalamus, a key regulator of metabolism in the central nervous system. We observed that the 3xtg-AD model exhibited significantly higher oxygen consumption as well as food intake before reported amyloid plaque formation, indicating that metabolic abnormalities occurred at early onset in the 3xtg-AD model compared with their counterparts. Analysis of gene expression in the hypothalamus indicated increased mRNA expression of inflammation- and apoptosis-related genes, as well as decreased gene expression of Agouti-related protein (AgRP and Melanocortin 4 receptor (MC4R at 12 weeks of age. Immunofluorescence analysis revealed that pro-opiomelanocortin (POMC and NPY-expressing neurons decreased at 24 weeks in the 3xtg-AD model. Four weeks of voluntary exercise were sufficient to reverse the gene expression of inflammation and apoptotic markers in the hypothalamus, six weeks of exercise improved glucose metabolism, moreover, 8 weeks of voluntary exercise training attenuated apoptosis and augmented POMC and NPY-expressing neuronal populations in the hypothalamus compared to the control group. Our results indicated that early onset of metabolic abnormalities may contribute to the pathology of AD, which is associated with increased inflammation as well as decreased neuronal population and key neuropeptides in the hypothalamus. Furthermore, early intervention by voluntary exercise normalized hypothalamic inflammation and neurodegeneration as well as glucose metabolism in the 3xtg-AD model. The data, taken as a whole, suggests a hypothalamic-mediated mechanism where exercise prevents the progression of dementia and of Alzheimer's disease.

  10. Increased migration of antigen presenting cells to newly-formed lymphatic vessels in transplanted kidneys by glycol-split heparin.

    Science.gov (United States)

    Talsma, Ditmer T; Katta, Kirankumar; Boersema, Miriam; Adepu, Saritha; Naggi, Annamaria; Torri, Giangiacomo; Stegeman, Coen; Navis, Gerjan; van Goor, Harry; Hillebrands, Jan-Luuk; Yazdani, Saleh; van den Born, Jacob

    2017-01-01

    Chronic renal transplant dysfunction is characterized by loss of renal function and tissue remodeling, including chronic inflammation and lymph vessel formation. Proteoglycans are known for their chemokine presenting capacity. We hypothesize that interruption of the lymphatic chemokine-proteoglycan interaction interferes with the lymphatic outflow of leukocytes from the renal graft and might decrease the anti-graft allo-immune response. In a rat renal chronic transplant dysfunction model (female Dark-Agouti to male Wistar Furth), chemokines were profiled by qRT-PCR in microdissected tubulo-interstitial tissue. Disruption of lymphatic chemokine-proteoglycan interaction was studied by (non-anticoagulant) heparin-derived polysaccharides in vitro and in renal allografts. The renal allograft function was assessed by rise in plasma creatinine and urea. Within newly-formed lymph vessels of transplanted kidneys, numerous CD45+ leukocytes were found, mainly MHCII+, ED-1-, IDO-, HIS14-, CD103- antigen presenting cells, most likely representing a subset of dendritic cells. Treatment of transplanted rats with regular heparin and two different (non-)anticoagulant heparin derivatives revealed worsening of kidney function only in the glycol-split heparin treated group despite a two-fold reduction of tubulo-interstitial leukocytes (plymphatic antigen-presenting cells only in the glycol-split heparin group (plymphatic leukocytes significantly correlates with plasma creatinine and urea, and inversely with creatinine clearance. Treatment of transplanted rats with glycol-split heparin significantly increases the number of intra-lymphatic antigen presenting cells, by increased renal diffusion of lymphatic chemokines, thereby increasing the activation and recruitment of antigen presenting cells towards the lymph vessel. This effect is unwanted in the transplantation setting, but might be advantageous in e.g., dendritic cell vaccination.

  11. Sex differences in the physiology of eating

    Science.gov (United States)

    Asarian, Lori

    2013-01-01

    Hypothalamic-pituitary-gonadal (HPG) axis function fundamentally affects the physiology of eating. We review sex differences in the physiological and pathophysiological controls of amounts eaten in rats, mice, monkeys, and humans. These controls result from interactions among genetic effects, organizational effects of reproductive hormones (i.e., permanent early developmental effects), and activational effects of these hormones (i.e., effects dependent on hormone levels). Male-female sex differences in the physiology of eating involve both organizational and activational effects of androgens and estrogens. An activational effect of estrogens decreases eating 1) during the periovulatory period of the ovarian cycle in rats, mice, monkeys, and women and 2) tonically between puberty and reproductive senescence or ovariectomy in rats and monkeys, sometimes in mice, and possibly in women. Estrogens acting on estrogen receptor-α (ERα) in the caudal medial nucleus of the solitary tract appear to mediate these effects in rats. Androgens, prolactin, and other reproductive hormones also affect eating in rats. Sex differences in eating are mediated by alterations in orosensory capacity and hedonics, gastric mechanoreception, ghrelin, CCK, glucagon-like peptide-1 (GLP-1), glucagon, insulin, amylin, apolipoprotein A-IV, fatty-acid oxidation, and leptin. The control of eating by central neurochemical signaling via serotonin, MSH, neuropeptide Y, Agouti-related peptide (AgRP), melanin-concentrating hormone, and dopamine is modulated by HPG function. Finally, sex differences in the physiology of eating may contribute to human obesity, anorexia nervosa, and binge eating. The variety and physiological importance of what has been learned so far warrant intensifying basic, translational, and clinical research on sex differences in eating. PMID:23904103

  12. Modulation of orexigenic and anorexigenic peptides gene expression in the rat DVC and hypothalamus by acute immobilization stress

    Directory of Open Access Journals (Sweden)

    Fatiha eChigr

    2014-07-01

    Full Text Available We studied the long term effects of a single exposure to immobilization stress (IS (1 hour on the expression of anorexigenic (Pro-opiomelanocortin: POMC and cocaine amphetamine related transcript: CART and orexigenic (neuropeptide Y:NPY, Agouti related peptide: AgRP factors in hypothalamus and dorso vagal complex (DVC. We showed, by using RT-PCR that in the hypothalamus, that the mRNAs of POMC and CART were up-regulated at the end of IS and up to 24 hours. This up regulation persists until 48-72h after IS for CART only. In the DVC, their expressions peak significantly at 24h post stress and decline afterwards; CART mRNA is down regulated after 48h post stress. NPY and AgRP mRNAs show a gradual increase just after the end of IS. The up regulation is significant only at 24 hours after stress for AgRP but remains significantly higher for NPY compared to controls. In DVC, the mRNAs of the two factors show generally a similar post stress pattern. A significant increase jut after the end of IS of rats which persists up to 24 hours after is firstly noticed. The levels tend then to reach the basal levels although, they were slightly but significantly higher up to 72 hours after stress for mRNA NPY. The comparison between the expression profiles of anorexigenic and the two orexigenic peptides investigated shows the presence of a parallelism between that of POMC and AgRP and that of CART and NPY when each brain region (hypothalamus and DVC is considered separately. It seems that any surge in the expression of each anorexigenic factor stimulates the expression of those of corresponding and appropriated orexigenic one. These last reactions from orexigenic peptides tend to attenuate the anorexigenic effects of CART and POMC and by consequent to abolish the anorexia state generated by stress.

  13. Sex Bias in Pathogenesis of Autoimmune Neuroinflammation: Relevance for Dimethyl Fumarate Immunomodulatory/Anti-oxidant Action.

    Science.gov (United States)

    Stojić-Vukanić, Zorica; Kotur-Stevuljević, Jelena; Nacka-Aleksić, Mirjana; Kosec, Duško; Vujnović, Ivana; Pilipović, Ivan; Dimitrijević, Mirjana; Leposavić, Gordana

    2017-05-22

    In the present study, upon showing sexual dimorphism in dimethyl fumarate (DMF) efficacy to moderate the clinical severity of experimental autoimmune encephalomyelitis (EAE) in Dark Agouti rats, cellular and molecular substrate of this dimorphism was explored. In rats of both sexes, DMF administration from the day of immunization attenuated EAE severity, but this effect was more prominent in males leading to loss of the sexual dimorphism observed in vehicle-administered controls. Consistently, in male rats, DMF was more efficient in diminishing the number of CD4+ T lymphocytes infiltrating spinal cord (SC) and their reactivation, the number of IL-17+ T lymphocytes and particularly cellularity of their highly pathogenic IFN-γ+GM-CSF+IL-17+ subset. This was linked with changes in SC CD11b+CD45+TCRαβ- microglia/proinflammatory monocyte progeny, substantiated in a more prominent increase in the frequency of anti-inflammatory phygocyting CD163+ cells and the cells expressing high surface levels of immunoregulatory CD83 molecule (associated with apoptotic cells phagocytosis and implicated in downregulation of CD4+ T lymphocyte reactivation) among CD11b+CD45+TCRαβ- cells in male rat SC. These changes were associated with greater increase in the nuclear factor (erythroid-derived 2)-like 2 expression in male rats administered with DMF. In accordance with the previous findings, DMF diminished reactive nitrogen and oxygen species generation and consistently, SC level of advanced oxidation protein products, to the greater extent in male rats. Overall, our study indicates sex-specificity in the sensitivity of DMF cellular and molecular targets and encourages sex-based clinical research to define significance of sex for action of therapeutic agents moderating autoimmune neuroinflammation-/oxidative stress-related nervous tissue damage.

  14. Hypothalamic effects of neonatal diet: reversible and only partially leptin dependent.

    Science.gov (United States)

    Sominsky, Luba; Ziko, Ilvana; Nguyen, Thai-Xinh; Quach, Julie; Spencer, Sarah J

    2017-07-01

    Early life diet influences metabolic programming, increasing the risk for long-lasting metabolic ill health. Neonatally overfed rats have an early increase in leptin that is maintained long term and is associated with a corresponding elevation in body weight. However, the immediate and long-term effects of neonatal overfeeding on hypothalamic anorexigenic pro-opiomelanocortin (POMC) and orexigenic agouti-related peptide (AgRP)/neuropeptide Y (NPY) circuitry, and if these are directly mediated by leptin, have not yet been examined. Here, we examined the effects of neonatal overfeeding on leptin-mediated development of hypothalamic POMC and AgRP/NPY neurons and whether these effects can be normalised by neonatal leptin antagonism in male Wistar rats. Neonatal overfeeding led to an acute (neonatal) resistance of hypothalamic neurons to exogenous leptin, but this leptin resistance was resolved by adulthood. While there were no effects of neonatal overfeeding on POMC immunoreactivity in neonates or adults, the neonatal overfeeding-induced early increase in arcuate nucleus (ARC) AgRP/NPY fibres was reversed by adulthood so that neonatally overfed adults had reduced NPY immunoreactivity in the ARC compared with controls, with no further differences in AgRP immunoreactivity. Short-term neonatal leptin antagonism did not reverse the excess body weight or hyperleptinaemia in the neonatally overfed, suggesting factors other than leptin may also contribute to the phenotype. Our findings show that changes in the availability of leptin during early life period influence the development of hypothalamic connectivity short term, but this is partly resolved by adulthood indicating an adaptation to the metabolic mal-programming effects of neonatal overfeeding. © 2017 Society for Endocrinology.

  15. Early postnatal amylin treatment enhances hypothalamic leptin signaling and neural development in the selectively bred diet-induced obese rat.

    Science.gov (United States)

    Johnson, Miranda D; Bouret, Sebastien G; Dunn-Meynell, Ambrose A; Boyle, Christina N; Lutz, Thomas A; Levin, Barry E

    2016-12-01

    Selectively bred diet-induced obese (DIO) rats become obese on a high-fat diet and are leptin resistant before becoming obese. Compared with diet-resistant (DR) neonates, DIO neonates have impaired leptin-dependent arcuate (ARC) neuropeptide Y/agouti-related peptide (NPY/AgRP) and α-melanocyte-stimulating hormone (α-MSH; from proopiomelanocortin (POMC) neurons) axon outgrowth to the paraventricular nucleus (PVN). Using phosphorylation of STAT3 (pSTAT3) as a surrogate, we show that reduced DIO ARC leptin signaling develops by postnatal day 7 (P7) and is reduced within POMC but not NPY/AgRP neurons. Since amylin increases leptin signaling in adult rats, we treated DIO neonates with amylin during postnatal hypothalamic development and assessed leptin signaling, leptin-dependent ARC-PVN pathway development, and metabolic changes. DIO neonates treated with amylin from P0-6 and from P0-16 increased ARC leptin signaling and both AgRP and α-MSH ARC-PVN pathway development, but increased only POMC neuron number. Despite ARC-PVN pathway correction, P0-16 amylin-induced reductions in body weight did not persist beyond treatment cessation. Since amylin enhances adult DIO ARC signaling via an IL-6-dependent mechanism, we assessed ARC-PVN pathway competency in IL-6 knockout mice and found that the AgRP, but not the α-MSH, ARC-PVN pathway was reduced. These results suggest that both leptin and amylin are important neurotrophic factors for the postnatal development of the ARC-PVN pathway. Amylin might act as a direct neurotrophic factor in DIO rats to enhance both the number of POMC neurons and their α-MSH ARC-PVN pathway development. This suggests important and selective roles for amylin during ARC hypothalamic development.

  16. Genetic basis of inter- and intrastrain differences in diazepam p-hydroxylation in rats.

    Science.gov (United States)

    Sakai, Noriaki; Saito, Konomu; Sakamoto, Kentaro Q; Ishizuka, Mayumi; Fujita, Shoichi

    2009-02-01

    Diazepam (7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one) is widely used as a sedative, hypnotic, and anti-anxiety drug. At low diazepam concentrations, p-hydroxylation is the major metabolic pathway in rat liver microsomes. However, there are marked ( approximately 300-fold) inter- and intrastrain differences in the activity among Sprague-Dawley, Brown Norway, Dark Agouti, and Wistar rats. In our previous study, we determined that a deficiency of CYP2D3 protein, not CYP2D2, was responsible for the inter- and intrastrain differences in diazepam p-hydroxylation (Drug Metab Dispos 33:1657-1660, 2005). Quantitative real-time polymerase chain reaction (PCR) did not provide enough evidence to explain the inter- and intrastrain differences in the expression of CYP2D3 protein. Nucleotide sequence analysis revealed the insertion of a thymine in exon 8 of the CYP2D3 gene in the poor diazepam metabolizers. This single nucleotide mutation caused a shift in the reading frame and introduced a premature termination signal. It is noteworthy that the heme binding region, which is essential to maintain proper heme binding and active cytochrome P450 enzymes, was consequently deleted by the premature termination signal. In contrast, no mutation was detected in the CYP2D3 gene of extensive metabolizers. Thus, the truncated CYP2D3 must be a nonfunctional enzyme in poor metabolizers. In addition, we developed a convenient and specific genotyping assay using PCR-restriction, fragment-length polymorphism to distinguish homozygotes from heterozygotes. The genotyping gave results fully consistent with those of the inter- and intrastrain differences in diazepam p-hydroxylation.

  17. Experimental autoimmune encephalomyelitis (EAE): lesion visualization on a 3 tesla Clinical whole-body system after intraperitoneal contrast injection

    Energy Technology Data Exchange (ETDEWEB)

    Heckl, S.; Naegele, T.; Klose, U. [Dept. of Neuroradiology, Medical School, Univ. of Tuebingen (Germany); Herrmann, M.; Gaertner, S.; Weissert, R. [Dept. of Neurology, Medical School, Univ. of Tuebingen (Germany); Schick, F. [Dept. of Radiology, Medical School, Univ. of Tuebingen (Germany); Kueker, W. [Dept. of Neuroradiology, Medical School, Univ. of Tuebingen (Germany); Dept. of Neuroradiology, Radcliffe Infirmary, Oxford, England (United Kingdom)

    2004-11-01

    Purpose: To investigate the intravital visibility of CNS lesions in rats with experimental autoimmune encephalomyelitis (EAE), the animal correlate of multiple sclerosis, using a 3-Tesla (T) wholebody MR system. Materials and Methods: Three healthy Dark Agouti (DA) rats and 16 DA rats with clinical signs of EAE were examined on a 3T whole body-system using a normal wrist coil. In total, 25 examinations were preformed using T2- and T1-weighted images in transverse and sagittal orientation with a slice thickness of 2 mm or 1 mm (voxel size up to 0.2 x 0.2 x 1 mm). Sedation was achieved by intraperitoneal injection of ketamine and xylazine. In addition, T1-weighted images were obtained after the instillation of 1.0 ml of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) (0.5 mmol/ml) into the peritoneal cavity. Results: T2- and T1-weighted images of the brain and spinal cord with high spatial and contrast resolution could be obtained in all animals. The anatomical details of the olfactory bulb glomeruli, cerebellum foliae, ventricles and corpus callosum were clearly visible. The EAE lesions presented as hyperintense area in T2-weighted images and could be demonstrated in all clinically affected animals by MRI and histologically verified. In total, the 16 affected rats had 28 cerebral and 2 spinal cord lesions (range 1 to 4, median 2). Contrast enhancement was noted in 12 animals and ranked as severe in ten and moderate in two cases. No adverse effects were noted due to sedation or intraperitoneal contrast injection. Conclusions: The intravital demonstration of cerebral and spinal cord EAE lesions in rats is possible on a 3T whole-body MR scanner using a normal wrist coil. Intraperitoneal injection of ketamine/xylazine and contrast agent is an easy, safe and effective procedure in rats. (orig.)

  18. Risperidone-induced weight gain and reduced locomotor activity in juvenile female rats: The role of histaminergic and NPY pathways.

    Science.gov (United States)

    Lian, Jiamei; De Santis, Michael; He, Meng; Deng, Chao

    2015-01-01

    Second generation antipsychotic drugs (SGAs) such as risperidone are increasingly prescribed (mostly for off-label use) to children and adolescents for treating various mental disorders. SGAs cause serious weight gain/obesity and other metabolic side-effects. This study aimed to establish an animal model of risperidone-induced weight gain in female juvenile rats, and to investigate the effects of risperidone on the expression of hypothalamic histaminergic H1 receptors (H1R) and neuropeptides, and their association with weight gain. Female Sprague Dawley rats were treated orally with risperidone (0.3mg/kg, 3 times/day) or vehicle (control) starting from postnatal day (PD) 23 (±1 day) for 3 weeks (a period corresponding to the childhood-adolescent period in humans). In the female juvenile rats, risperidone treatment increased food intake and body weight gain, which started to appear after 12 days' treatment. Risperidone also significantly decreased the locomotor activity of the female rats. Consistently, risperidone significantly elevated mRNA expression of hypothalamic H1R, neuropeptide Y (NPY), and agouti-related peptide (AgRP) compared to controls, and H1R and NPY levels were correlated with risperidone enhanced weight gain and food intake in the female juvenile rats. However, risperidone did not affect hypothalamic proopiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) mRNA expression. Therefore, these results suggested that risperidone elevated appetite and body weight gain in juveniles via regulation of the hypothalamic H1R, NPY and AgRP pathways, as well as by reducing activity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Involvement of the melanocortin-1 receptor in acute pain and pain of inflammatory but not neuropathic origin.

    Directory of Open Access Journals (Sweden)

    Ada Delaney

    2010-09-01

    Full Text Available Response to painful stimuli is susceptible to genetic variation. Numerous loci have been identified which contribute to this variation, one of which, MC1R, is better known as a gene involved in mammalian hair colour. MC1R is a G protein-coupled receptor expressed in melanocytes and elsewhere and mice lacking MC1R have yellow hair, whilst humans with variant MC1R protein have red hair. Previous work has found differences in acute pain perception, and response to analgesia in mice and humans with mutations or variants in MC1R.We have tested responses to noxious and non-noxious stimuli in mutant mice which lack MC1R, or which overexpress an endogenous antagonist of the receptor, as well as controls. We have also examined the response of these mice to inflammatory pain, assessing the hyperalgesia and allodynia associated with persistent inflammation, and their response to neuropathic pain. Finally we tested by a paired preference paradigm their aversion to oral administration of capsaicin, which activates the noxious heat receptor TRPV1. Female mice lacking MC1R showed increased tolerance to noxious heat and no alteration in their response to non-noxious mechanical stimuli. MC1R mutant females, and females overexpressing the endogenous MC1R antagonist, agouti signalling protein, had a reduced formalin-induced inflammatory pain response, and a delayed development of inflammation-induced hyperalgesia and allodynia. In addition they had a decreased aversion to capsaicin at moderate concentrations. Male mutant mice showed no difference from their respective controls. Mice of either sex did not show any effect of mutant genotype on neuropathic pain.We demonstrate a sex-specific role for MC1R in acute noxious thermal responses and pain of inflammatory origin.

  20. A Novel Analytical Strategy to Identify Fusion Transcripts between Repetitive Elements and Protein Coding-Exons Using RNA-Seq

    Science.gov (United States)

    Feng, Jian; Fargo, David C.; Shen, Li; Riadi, Gonzalo; Keeley, Elizabeth; Rosh, Zachary S.; Nestler, Eric J.; Woychik, Richard P.

    2016-01-01

    Repetitive elements (REs) comprise 40–60% of the mammalian genome and have been shown to epigenetically influence the expression of genes through the formation of fusion transcript (FTs). We previously showed that an intracisternal A particle forms an FT with the agouti gene in mice, causing obesity/type 2 diabetes. To determine the frequency of FTs genome-wide, we developed a TopHat-Fusion-based analytical pipeline to identify FTs with high specificity. We applied it to an RNA-seq dataset from the nucleus accumbens (NAc) of mice repeatedly exposed to cocaine. Cocaine was previously shown to increase the expression of certain REs in this brain region. Using this pipeline that can be applied to single- or paired-end reads, we identified 438 genes expressing 813 different FTs in the NAc. Although all types of studied repeats were present in FTs, simple sequence repeats were underrepresented. Most importantly, reverse-transcription and quantitative PCR validated the expression of selected FTs in an independent cohort of animals, which also revealed that some FTs are the prominent isoforms expressed in the NAc by some genes. In other RNA-seq datasets, developmental expression as well as tissue specificity of some FTs differed from their corresponding non-fusion counterparts. Finally, in silico analysis predicted changes in the structure of proteins encoded by some FTs, potentially resulting in gain or loss of function. Collectively, these results indicate the robustness of our pipeline in detecting these new isoforms of genes, which we believe provides a valuable tool to aid in better understanding the broad role of REs in mammalian cellular biology. PMID:27415830

  1. Adipose tissue and reproductive health.

    Science.gov (United States)

    Mathew, Hannah; Castracane, V Daniel; Mantzoros, Christos

    2017-11-16

    The understanding of adipose tissue role has evolved from that of a depot energy storage organ to a dynamic endocrine organ. While genetics, sexual phenotype and sex steroids can impact the mass and distribution of adipose tissue, there is a counter-influence of white adipocytes on reproduction. This primarily occurs via the secretion of adipokines, the most studied of which- leptin and adiponectin- are highlighted in this article. Leptin, the "satiety hormone" primarily acts on the hypothalamus via pro-opiomelanocortin (POMC), neuropeptide Y (NPY), and agouti-related peptide (AgRP) neurons to translate acute changes in nutrition and energy expenditure, as well as chronic adipose accumulation into changes in appetite and potentially mediate insulin resistance via shared pathway and notably impacting reproductive health via influence on GnRH secreting neurons. Meanwhile, adiponectin is notable for its action in mediating insulin sensitivity, with receptors found at every level of the reproductive axis. Both have been examined in the context of physiologic and pathologic reproductive conditions. Leptin has been shown to influence puberty, pregnancy, hypothalamic amenorrhea, and lipodystrophy, and with a potential therapeutic role for both metabolic and reproductive health. Adiponectin mediates the relative state of insulin resistance in pregnancy, and has been implicated in conditions such as polycystic ovary syndrome and reproductive malignancies. There are numerous other adipokines, including resistin, visfatin, chemerin and retinol binding protein-4, which may also play roles in reproductive health and disease states. The continued examination of these and other adipokines in both normal reproduction and reproductive pathologies represents an important avenue for continued study. Here, we seek to provide a broad, yet comprehensive overview of many facets of these relationships and highlight areas of consideration for clinicians and future study. Copyright © 2017

  2. Essential role of UCP1 modulating the central effects of thyroid hormones on energy balance

    Science.gov (United States)

    Alvarez-Crespo, Mayte; Csikasz, Robert I.; Martínez-Sánchez, Noelia; Diéguez, Carlos; Cannon, Barbara; Nedergaard, Jan; López, Miguel

    2016-01-01

    Objective Classically, metabolic effects of thyroid hormones (THs) have been considered to be peripherally mediated, i.e. different tissues in the body respond directly to thyroid hormones with an increased metabolism. An alternative view is that the metabolic effects are centrally regulated. We have examined here the degree to which prolonged, centrally infused triiodothyronine (T3) could in itself induce total body metabolic effects and the degree to which brown adipose tissue (BAT) thermogenesis was essential for such effects, by examining uncoupling protein 1 (UCP1) KO mice. Methods Wildtype and UPC1 KO mice were centrally-treated with T3 by using minipumps. Metabolic measurements were analyzed by indirect calorimetry and expression analysis by RT-PCR or western blot. BAT morphology and histology were studied by immunohistochemistry. Results We found that central T3-treatment led to reduced levels of hypothalamic AMP-activated protein kinase (AMPK) and elevated body temperature (0.7 °C). UCP1 was essential for the T3-induced increased rate of energy expenditure, which was only observable at thermoneutrality and notably only during the active phase, for the increased body weight loss, for the increased hypothalamic levels of neuropeptide Y (NPY) and agouti-related peptide (AgRP) and for the increased food intake induced by central T3-treatment. Prolonged central T3-treatment also led to recruitment of BAT and britening/beiging (“browning”) of inguinal white adipose tissue (iWAT). Conclusions We conclude that UCP1 is essential for mediation of the central effects of thyroid hormones on energy balance, and we suggest that similar UCP1-dependent effects may underlie central energy balance effects of other agents. PMID:27069867

  3. Hunger States Control the Directions of Synaptic Plasticity via Switching Cell Type-Specific Subunits of NMDA Receptors.

    Science.gov (United States)

    Qi, Yong; Yang, Yunlei

    2015-09-23

    It remains largely unknown whether and how hunger states control activity-dependent synaptic plasticity, such as long-term potentiation (LTP) and long-term depression (LTD). We here report that both LTP and LTD of excitatory synaptic strength within the appetite control circuits residing in hypothalamic arcuate nucleus (ARC) behave in a manner of hunger states dependence and cell type specificity. For instance, we find that tetanic stimulation induces LTP at orexigenic agouti-related protein (AgRP) neurons in ad libitum fed mice, whereas it induces LTD in food-deprived mice. In an opposite direction, the same induction protocol induces LTD at anorexigenic pro-opiomelanocortin (POMC) neurons in fed mice but weak LTP in deprived mice. Mechanistically, we also find that food deprivation increases the expressions of NR2C/NR2D/NR3-containing NMDA receptors (NMDARs) at AgRP neurons that contribute to the inductions of LTD, whereas it decreases their expressions at POMC neurons. Collectively, our data reveal that hunger states control the directions of activity-dependent synaptic plasticity by switching NMDA receptor subpopulations in a cell type-specific manner, providing insights into NMDAR-mediated interactions between energy states and associative memory. Significance statement: Based on the experiments performed in this study, we demonstrate that activity-dependent synaptic plasticity is also under the control of energy states by regulating NMDAR subpopulations in a cell type-specific manner. We thus propose a reversible memory configuration constructed from energy states-dependent cell type-specific bidirectional conversions of LTP and LTD. Together with the distinct functional roles played by NMDAR signaling in the control of food intake and energy states, these findings reveal a new reciprocal interaction between energy states and associative memory, one that might serve as a target for therapeutic treatments of the energy-related memory disorders or vice versa

  4. Stress-induced suppression of neuropeptide Y-induced hunger in anorexic chicks involves corticotrophin-releasing factor signalling and the paraventricular nucleus of the hypothalamus.

    Science.gov (United States)

    Wang, J; Yi, J; Siegel, P B; Cline, M A; Gilbert, E R

    2017-12-01

    The Virginia lines of chickens have been selected for low (LWS) or high (HWS) juvenile body weight and have different severities of anorexia and obesity, respectively. The LWS that are exposed to stressors at hatch are refractory to neuropeptide Y (NPY)-induced food intake and the objective of the present study was to determine the underlying mechanisms. Chicks were exposed to a stressor (-20°C for 6 minutes and 22°C and delayed access to food for 24 hours) after hatching and the hypothalamic nuclei, including the lateral hypothalamus (LH), paraventricular nucleus (PVN), ventromedial hypothalamus (VMH) and arcuate nucleus (ARC), were collected 5 days later. In LWS but not HWS, stress exposure up-regulated corticotrophin-releasing factor (CRF), CRF receptor subtypes 1 and 2 (CRFR1 and CRFR2, respectively), melanocortin receptor 4 and urocortin 3 in the PVN, as well as CRFR2 mRNA in the VMH and ARC. In LWS, stress exposure was also associated with greater NPY and NPY receptor subtype 5 mRNA in the ARC and PVN, respectively, as well as decreased agouti-related peptide mRNA in the ARC. In HWS, stress exposure was associated with increased CRFR1 and decreased cocaine- and amphetamine-regulated transcript in the ARC and PVN, respectively. Refractoriness of the food intake response to NPY in LWS may thus result from the over-riding anorexigenic tone in the PVN associated with CRF signalling. Indeed, the orexigenic effect of NPY was restored when LWS were injected with a CRF receptor antagonist, astressin, before stress exposure. The results of the present study provide insights into the molecular basis of eating disorders and suggest that CRF signalling in the PVN may exacerbate the anorexic phenotype in the presence of environmental stressors. © 2017 British Society for Neuroendocrinology.

  5. The central effects of alpha-melanocyte stimulating hormone (α-MSH) in chicks involve changes in gene expression of neuropeptide Y and other factors in distinct hypothalamic nuclei.

    Science.gov (United States)

    Delp, Meghan S; Cline, Mark A; Gilbert, Elizabeth R

    2017-06-09

    Alpha-melanocyte stimulating hormone (α-MSH) is a satiety-inducing factor in birds and mammals although central mechanisms mediating its effects on appetite in birds are poorly understood. Thus, the objective of the present study was to determine effects of centrally-injected α-MSH on c-Fos and gene expression in chick appetite-associated hypothalamic nuclei. At 4days post-hatch, 3h-fasted chicks were intracerebroventricularly (ICV) injected with 0 (vehicle) or 0.12nmol α-MSH and 1h later, hypothalamus samples were collected for measuring c-Fos immunoreactivity and mRNA abundance of appetite-associated factors in hypothalamic nuclei. There were more c-Fos immunoreactive cells in the arcuate nucleus (ARC), dorsomedial nucleus (DMN), lateral hypothalamus (LH), and paraventricular nucleus (PVN) of α-MSH- than vehicle-injected chicks. Neuropeptide Y (NPY), oxytocin receptor (OXTR), and agouti-related peptide (AgRP) mRNAs were greater in α-MSH- than vehicle-injected chicks in the ARC. In the PVN, NPY receptor sub-type 1 (NPYR1) mRNA was reduced while c-Fos mRNA was increased in response to treatment with α-MSH. NPY, c-Fos, and DOPA decarboxylase (DDC) mRNAs were greater in treated than vehicle-injected chicks in the DMN. Results suggest that during the first hour post-injection, the appetite-inhibiting effects of α-MSH involve activation of the ARC, DMN, PVN, and LH, and corresponding changes in transcriptional regulation of factors involved with NPY, AgRP and mesotocin signaling, and monoamine synthesis. The effects of these changes may include an inhibition of NPY signaling in the PVN to induce satiety and stimulation of NPY/AgRP neurons in the ARC in an attempt to restore homeostatic levels of food intake. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Myosin Va plays a role in nitrergic smooth muscle relaxation in gastric fundus and corpora cavernosa of penis.

    Directory of Open Access Journals (Sweden)

    Arun Chaudhury

    Full Text Available The intracellular motor protein myosin Va is involved in nitrergic neurotransmission possibly by trafficking of neuronal nitric oxide synthase (nNOS within the nerve terminals. In this study, we examined the role of myosin Va in the stomach and penis, proto-typical smooth muscle organs in which nitric oxide (NO mediated relaxation is critical for function. We used confocal microscopy and co-immunoprecipitation of tissue from the gastric fundus (GF and penile corpus cavernosum (CCP to localize myosin Va with nNOS and demonstrate their molecular interaction. We utilized in vitro mechanical studies to test whether smooth muscle relaxations during nitrergic neuromuscular neurotransmission is altered in DBA (dilute, brown, non-agouti mice which lack functional myosin Va. Myosin Va was localized in nNOS-positive nerve terminals and was co-immunoprecipitated with nNOS in both GF and CCP. In comparison to C57BL/6J wild type (WT mice, electrical field stimulation (EFS of precontracted smooth muscles of GF and CCP from DBA animals showed significant impairment of nitrergic relaxation. An NO donor, Sodium nitroprusside (SNP, caused comparable levels of relaxation in smooth muscles of WT and DBA mice. These normal postjunctional responses to SNP in DBA tissues suggest that impairment of smooth muscle relaxation resulted from inhibition of NO synthesis in prejunctional nerve terminals. Our results suggest that normal physiological processes of relaxation of gastric and cavernosal smooth muscles that facilitate food accommodation and penile erection, respectively, may be disrupted under conditions of myosin Va deficiency, resulting in complications like gastroparesis and erectile dysfunction.

  7. Micro RNA-155 participates in re-activation of encephalitogenic T cells.

    Science.gov (United States)

    Jevtić, Bojan; Timotijević, Gordana; Stanisavljević, Suzana; Momčilović, Miljana; Mostarica Stojković, Marija; Miljković, Djordje

    2015-08-01

    MicroRNAs (miR) are small non-coding RNAs involved in the immune response regulation. miR-155 has been attributed a major pro-inflammatory role in the pathogenesis of multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). Here, a role of miR-155 in re-activation of encephalitogenic CD4(+) T cells was investigated. Dark Agouti rats were immunized with myelin basic protein (MBP) emulsified in complete Freund's adjuvant. CD4(+) T cells were purified from draining lymph node cells (DLNC) obtained in the inductive phase and from spinal cord immune cells (SCIC) isolated at the peak of EAE. CD4(+) T cells obtained from SCIC (i.e., in vivo re-activated cells) had markedly higher expression of miR-155 in comparison to those purified from DLNC (not re-activated). Likewise, in vitro re-activation of DLNC with MBP led to increase in miR-155 expression. Further, DLNC and DLNC CD4(+) T cells were transfected with an inhibitor of miR-155 during in vitro re-activation. As a result, expression of important CD4(+) T cell effector cytokines IFN-γ and IL-17, but not of regulatory cytokines IL-10 and TGF-β, was reduced. These results imply that miR-155 supports re-activation of encephalitogenic CD4(+) T cells. Our results contribute to a view that miR-155 might be a valuable target in multiple sclerosis therapy. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  8. Surface wetting strategy prevents acute heat exposure-induced alterations of hypothalamic stress- and metabolic-related genes in broiler chickens.

    Science.gov (United States)

    Rajaei-Sharifabadi, H; Greene, E; Piekarski, A; Falcon, D; Ellestad, L; Donoghue, A; Bottje, W; Porter, T; Liang, Y; Dridi, S

    2017-03-01

    Heat stress (HS) is devastating to poultry production worldwide, yet its biology and molecular responses are not well defined. Although advances in management strategy have partially alleviated the negative impact of HS, productivity still continues to decline when the ambient temperature rises. Therefore, identifying mechanism-based approaches to decrease HS susceptibility while improving production traits is critical. Recently, we made a breakthrough by applying a surface wetting strategy and showing that it improves growth performance compared with the current conventional cooling system. In the present study, we aimed to further define molecular mechanisms associated with surface wetting in ameliorating HS productivity loss in broilers. Five-week-old broiler chickens were exposed to acute HS (35°C for 2 h) alone or in combination with surface wetting. A control group was maintained at thermoneutral conditions (25°C). Core body temperature (BT) and feed intake were recorded. Blood was collected and hypothalamic tissues (main site involved in the regulation of energy homeostasis) were harvested to determine the expression profile of stress- and metabolic-related genes. Surface wetting prevents HS from increasing BT and plasma corticosterone levels ( < 0.05) and improves feeding and drinking behaviors. At molecular levels, surface wetting blocks the activation of hypothalamic heat shock protein and adenosine monophosphate-activated protein-induced by HS and significantly modulates the expression of feeding-related hypothalamic neuropeptides (agouti-related protein, proopiomelanocortin, orexin, orexin receptor, and leptin receptor). Taken together, our data represent the first evidence that surface wetting alleviates systemic and intracellular stress induced by HS and preserves the intracellular energy status, which, in turn, may result in improved broiler well-being and growth performance.

  9. Enhanced susceptibility of ovaries from obese mice to 7,12-dimethylbenz[a]anthracene-induced DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    Ganesan, Shanthi, E-mail: shanthig@iastate.edu; Nteeba, Jackson, E-mail: nteeba@iastate.edu; Keating, Aileen F., E-mail: akeating@iastate.edu

    2014-12-01

    7,12-Dimethylbenz[a]anthracene (DMBA) depletes ovarian follicles and induces DNA damage in extra-ovarian tissues, thus, we investigated ovarian DMBA-induced DNA damage. Additionally, since obesity is associated with increased offspring birth defect incidence, we hypothesized that a DMBA-induced DNA damage response (DDR) is compromised in ovaries from obese females. Wild type (lean) non agouti (a/a) and KK.Cg-Ay/J heterozygote (obese) mice were dosed with sesame oil or DMBA (1 mg/kg; intraperitoneal injection) at 18 weeks of age, for 14 days. Total ovarian RNA and protein were isolated and abundance of Ataxia telangiectasia mutated (Atm), X-ray repair complementing defective repair in Chinese hamster cells 6 (Xrcc6), breast cancer type 1 (Brca1), Rad 51 homolog (Rad51), poly [ADP-ribose] polymerase 1 (Parp1) and protein kinase, DNA-activated, catalytic polypeptide (Prkdc) were quantified by RT-PCR or Western blot. Phosphorylated histone H2AX (γH2AX) level was determined by Western blotting. Obesity decreased (P < 0.05) basal protein abundance of PRKDC and BRCA1 proteins but increased (P < 0.05) γH2AX and PARP1 proteins. Ovarian ATM, XRCC6, PRKDC, RAD51 and PARP1 proteins were increased (P < 0.05) by DMBA exposure in lean mice. A blunted DMBA-induced increase (P < 0.05) in XRCC6, PRKDC, RAD51 and BRCA1 was observed in ovaries from obese mice, relative to lean counterparts. Taken together, DMBA exposure induced γH2AX as well as the ovarian DDR, supporting that DMBA causes ovarian DNA damage. Additionally, ovarian DDR was partially attenuated in obese females raising concern that obesity may be an additive factor during chemical-induced ovotoxicity. - Highlights: • DMBA induces markers of ovarian DNA damage. • Obesity induces low level ovarian DNA damage. • DMBA-induced DNA repair response is altered by obesity.

  10. Myosin Va Plays a Role in Nitrergic Smooth Muscle Relaxation in Gastric Fundus and Corpora Cavernosa of Penis

    Science.gov (United States)

    Carew, Josephine A.; Goyal, Raj K.; Sullivan, Maryrose P.

    2014-01-01

    The intracellular motor protein myosin Va is involved in nitrergic neurotransmission possibly by trafficking of neuronal nitric oxide synthase (nNOS) within the nerve terminals. In this study, we examined the role of myosin Va in the stomach and penis, proto-typical smooth muscle organs in which nitric oxide (NO) mediated relaxation is critical for function. We used confocal microscopy and co-immunoprecipitation of tissue from the gastric fundus (GF) and penile corpus cavernosum (CCP) to localize myosin Va with nNOS and demonstrate their molecular interaction. We utilized in vitro mechanical studies to test whether smooth muscle relaxations during nitrergic neuromuscular neurotransmission is altered in DBA (dilute, brown, non-agouti) mice which lack functional myosin Va. Myosin Va was localized in nNOS-positive nerve terminals and was co-immunoprecipitated with nNOS in both GF and CCP. In comparison to C57BL/6J wild type (WT) mice, electrical field stimulation (EFS) of precontracted smooth muscles of GF and CCP from DBA animals showed significant impairment of nitrergic relaxation. An NO donor, Sodium nitroprusside (SNP), caused comparable levels of relaxation in smooth muscles of WT and DBA mice. These normal postjunctional responses to SNP in DBA tissues suggest that impairment of smooth muscle relaxation resulted from inhibition of NO synthesis in prejunctional nerve terminals. Our results suggest that normal physiological processes of relaxation of gastric and cavernosal smooth muscles that facilitate food accommodation and penile erection, respectively, may be disrupted under conditions of myosin Va deficiency, resulting in complications like gastroparesis and erectile dysfunction. PMID:24516539

  11. Differential responses of orexigenic neuropeptides to fasting in offspring of obese mothers.

    Science.gov (United States)

    Chen, Hui; Morris, Margaret J

    2009-07-01

    Maternal obesity due to long-term high-fat diet (HFD) consumption leads to faster growth in offspring during suckling, and increased adiposity at 20 days of age. Decreased expression of the orexigenic neuropeptide Y (NPY) and increased anorexigenic proopiomelanocortin (POMC) mRNA expression were observed in the fed state. However, hunger is the major drive to eat and hypothalamic appetite regulators change in response to meals. Therefore, it is important to compare both satiated and fasting states. Female Sprague-Dawley rats (8 weeks old) were fed a cafeteria-style HFD (15.33 kJ/g) or chow for 5 weeks before mating, with the same diet continuing throughout gestation and lactation. At postnatal day 20, male pups were killed either after overnight fasting or in the fed state. Pups from obese dams were hyperphagic during both pre- and postweaning periods. Pups from obese dams had higher hypothalamic mRNA expression of POMC and NPY Y1 receptor, but lower hypothalamic melanocortin-4 receptor (MC4R) and its downstream target single-minded gene 1 (Sim1), in the fed state. Overnight fasting reduced circulating glucose, insulin, and leptin and increased hypothalamic NPY Y1 receptor mRNA in pups from both lean and obese dams. Hypothalamic NPY and agouti-related protein (AgRP) were only increased by fasting in pups from obese dams; reductions in MC4R and Sim1 were only seen in pups from lean dams. At weaning, the suppressed orexigenic signals in offspring from obese dams were normalized after overnight fasting, although anorexigenic signaling appeared impaired in these animals. This may contribute to their hyperphagia and faster growth.

  12. Alloimmune activation promotes anti-cancer cytotoxicity after rat liver transplantation.

    Directory of Open Access Journals (Sweden)

    Stéphanie Lacotte

    Full Text Available Liver transplantation for hepatocellular carcinoma (HCC results in a specific condition where the immune response is potentially directed against both allogeneic and cancer antigens. We have investigated the level of anti-cancer immunity during allogeneic immune response. Dark Agouti-to-Lewis and Lewis-to-Lewis rat liver transplantations were performed and the recipients anti-cancer immunity was analysed at the time of alloimmune activation. The occurrence of rejection in the allogeneic recipients was confirmed by a shorter survival (p<0.01, increased liver function tests (p<0.01, the presence of signs of rejection on histology, and a donor-specific ex vivo mixed lymphocyte reaction. At the time of alloimmune activation, blood mononuclear cells of the allogeneic group demonstrated increased anti-cancer cytotoxicity (p<0.005, which was related to an increased natural killer (NK cell frequency (p<0.05 and a higher monocyte/macrophage activation level (p<0.01. Similarly, liver NK cell anti-cancer cytotoxicity (p<0.005, and liver monocyte/macrophage activation levels (p<0.01 were also increased. The alloimmune-associated cytotoxicity was mediated through the NKG2D receptor, whose expression was increased in the rejected graft (p<0.05 and on NK cells and monocyte/macrophages. NKG2D ligands were expressed on rat HCC cells, and its inhibition prevented the alloimmune-associated cytotoxicity. Although waiting for in vivo validation, alloimmune-associated cytotoxicity after rat liver transplantation appears to be linked to increased frequencies and levels of activation of NK cells and monocyte/macrophages, and is at least in part mediated through the NKG2D receptor.

  13. Quantitative trait loci that control plasma lipid levels in an F2 intercross between C57BL/6J and DDD.Cg-A(y) inbred mouse strains.

    Science.gov (United States)

    Suto, Jun-ichi

    2012-04-01

    The objectives of this study were to characterize plasma lipid phenotypes and dissect the genetic basis of plasma lipid levels in an obese DDD.Cg-A(y) mouse strain. Plasma triglyceride (TG) levels were significantly higher in the DDD.Cg-A(y) strain than in the B6.Cg-A(y) strain. In contrast, plasma total-cholesterol (CHO) levels did not substantially differ between the two strains. As a rule, the A(y) allele significantly increased TG levels, but did not increase CHO levels. Quantitative trait locus (QTL) analyses for plasma TG and CHO levels were performed in two types of F(2) female mice [F(2)A(y) (F(2) mice carrying the A(y) allele) and F(2) non- A(y) mice (F(2) mice without the A(y) allele)] produced by crossing C57BL/6J females and DDD.Cg-A(y) males. Single QTL scan identified one significant QTL for TG levels on chromosome 1, and two significant QTLs for CHO levels on chromosomes 1 and 8. When the marker nearest to the QTL on chromosome 1 was used as covariates, four additional significant QTLs for CHO levels were identified on chromosomes 5, 6, and 17 (two loci). In contrast, consideration of the agouti locus genotype as covariates did not detect additional QTLs. DDD.Cg-A(y) showed a low CHO level, although it had Apoa2(b), which was a CHO-increasing allele at the Apoa2 locus. This may have been partly due to the presence of multiple QTLs, which were associated with decreased CHO levels, on chromosome 8.

  14. Further characterization of diabetes mellitus and body weight loss in males of the congenic mouse strain DDD.Cg-Ay

    Science.gov (United States)

    SUTO, Jun-ichi; SATOU, Kunio

    2014-01-01

    The Ay allele at the agouti locus causes obesity and promotes linear growth in mice. However, body weight gain stops between 16 and 17 weeks after birth, and then, body weight decreases gradually in DDD.Cg-Ay male mice. Body weight loss is a consequence of diabetes mellitus, which is genetically controlled mainly by a quantitative trait locus (QTL) on chromosome 4. This study aimed to further characterize diabetes mellitus and body weight loss in DDD.Cg-Ay males. The number of β-cells was markedly reduced, and plasma insulin levels were very low in the DDD.Cg-Ay males. Using a backcross progeny of DDD × (B6 × DDD.Cg-Ay) F1-Ay, we identified one significant QTL for plasma insulin levels on distal chromosome 4, which was coincidental with QTL for hyperglycemia and lower body weight. The DDD allele was associated with decreased plasma insulin levels. When the DDD.Cg-Ay males were housed under three different housing conditions [group housing (4 or 5 DDD.Cg-Ay and DDD males), individual housing (single DDD.Cg-Ay male) and single male housing with females (single DDD.Cg-Ay male with DDD.Cg-Ay or DDD females)], diabetes mellitus and body weight loss were most severely expressed in individually housed mice. Thus, the severity of diabetes and body weight loss in the DDD.Cg-Ay males was strongly influenced by the housing conditions. These results demonstrate that both genetic and nongenetic environmental factors are involved in the development of diabetes mellitus and body weight loss in the DDD.Cg-Ay males. PMID:25373882

  15. QTL mapping of genes controlling plasma insulin and leptin concentrations: metabolic effect of obesity QTLs identified in an F2 intercross between C57BL/6J and DDD.Cg-A(y) inbred mice.

    Science.gov (United States)

    Suto, Jun-ichi

    2013-07-31

    DDD.Cg-A(y) female mice developed massive obesity as compared with B6.Cg-A(y) female mice. We previously identified quantitative trait loci (QTLs) for obesity on chromosomes 1, 6, 9 and 17 in F2 female mice, including F2A(y) (F2 mice with the A(y) allele) and F2 non- A(y) mice (F2 mice without the A(y) allele), produced by crossing C57BL/6J and DDD.Cg-A(y) strains. We here addressed the question whether the obesity QTLs share genetic bases with putative QTLs for plasma glucose, insulin and leptin concentrations. We performed QTL analyses for the first principal component (PC1) extracted from these metabolic measurements to identify the genes that contributed to the comprehensive evaluation of metabolic traits. By single QTL scans, we identified two significant QTLs for insulin concentration on chromosomes 6 and 12, three for leptin concentration on chromosomes 1, 6 and 17, and five for PC1 on chromosomes 1, 6, 12 (two loci) and 17. Although insulin and leptin concentrations and PC1 were not normally distributed in combined F2 mice, results of single QTL scans by parametric and non-parametric methods were very similar. Therefore, QTL scan by the parametric method was performed with the agouti locus genotype as a covariate. A significant QTL × covariate interaction was found for PC1 on chromosome 9. All obesity QTLs had significant metabolic effects. Thus, obesity- and diabetes-related traits in DDD.Cg-A(y) mice were largely controlled by QTLs on chromosomes 1, 6, 9, 12 and 17.

  16. Suppression of GHS-R in AgRP Neurons Mitigates Diet-Induced Obesity by Activating Thermogenesis

    Science.gov (United States)

    Wu, Chia-Shan; Bongmba, Odelia Y. N.; Yue, Jing; Lee, Jong Han; Lin, Ligen; Saito, Kenji; Pradhan, Geetali; Li, De-Pei; Pan, Hui-Lin; Xu, Allison; Guo, Shaodong; Xu, Yong; Sun, Yuxiang

    2017-01-01

    Ghrelin, an orexigenic hormone released primarily from the gut, signals the hypothalamus to stimulate growth hormone release, enhance appetite and promote weight gain. The ghrelin receptor, aka Growth Hormone Secretagogue Receptor (GHS-R), is highly expressed in the brain, with highest expression in Agouti-Related Peptide (AgRP) neurons of the hypothalamus. We recently reported that neuron-specific deletion of GHS-R completely prevents diet-induced obesity (DIO) in mice by activating non-shivering thermogenesis. To further decipher the specific neuronal circuits mediating the metabolic effects of GHS-R, we generated AgRP neuron-specific GHS-R knockout mice (AgRP-Cre;Ghsrf/f). Our data showed that GHS-R in AgRP neurons is required for ghrelin’s stimulatory effects on growth hormone secretion, acute food intake and adiposity, but not for long-term total food intake. Importantly, deletion of GHS-R in AgRP neurons attenuated diet-induced obesity (DIO) and enhanced cold-resistance in mice fed high fat diet (HFD). The HFD-fed knockout mice showed increased energy expenditure, and exhibited enhanced thermogenic activation in both brown and subcutaneous fat; this implies that GHS-R suppression in AgRP neurons enhances sympathetic outflow. In summary, our results suggest that AgRP neurons are key site for GHS-R mediated thermogenesis, and demonstrate that GHS-R in AgRP neurons plays crucial roles in governing energy utilization and pathogenesis of DIO. PMID:28420089

  17. Rolling Nagoya mouse strain (PROD-rol/rol) with classic piebald mutation.

    Science.gov (United States)

    Yoshimoto, Takuro; Aoyama, Yo; Kim, Tae Yeon; Niimi, Kimie; Takahashi, Eiki; Itakura, Chitoshi

    2014-08-01

    Ataxic rolling Nagoya (PROD-rol/rol) mice, which carry a mutation in the α1 subunit of the Cav2.1 channel (Cacna1a) gene, were discovered in 1969. They show white spots on agouti coat and have a mutation in the piebald spotting (s) locus. However, mutation analysis of the s locus encoding the endothelin receptor type B (Ednrb) gene in PROD-rol/rol mice had not been performed. Here, we examined the genomic and mRNA sequences of the Ednrb gene in PROD-rol/rol and wild-type rolling Nagoya (PROD-s/s) and studied the expression patterns of Ednrb and Cacna1a genes in these mice in comparison with C57BL/6J mice. Polymerase chain reaction analyses revealed two silent nucleotide substitutions in the coding region and insertion of a retroposon-like element in intron 1 of the Ednrb gene. Expression analyses demonstrated similar localizations and levels of Ednrb and Cacna1a expression in the colon between PROD-rol/rol and PROD-s/s mice, but the expression levels of both genes were diminished compared with C57BL/6J mice. Microsatellite genotyping showed that at least particular regions of chromosome 14 proximal to the Ednrb locus of the PROD strain were derived from Japanese fancy piebald mice. These results indicated that PROD-rol/rol mice have two mutant genes, Ednrb and Cacna1a. As no PROD strain had an intact Ednrb gene, using congenic rolling mice would better serve to examine rolling Nagoya-type Cav2.1 channel dysfunctions.

  18. Adipose tissue as an endocrine organ.

    Science.gov (United States)

    Ahima, Rexford S

    2006-08-01

    Adipose tissue plays a critical role in energy homeostasis, not only in storing triglycerides, but also responding to nutrient, neural, and hormonal signals and secreting adipokines that control feeding, thermogenesis, immunity, and neuroendocrine function. A rise in leptin signals satiety to the brain through receptors in hypothalamic and brainstem neurons. Leptin activates tyrosine kinase, Janus kinase 2, and signal transducer and activator of transcription 3, leading to increased levels of anorexigenic peptides, e.g., alpha-melanocyte stimulating hormone and cocaine- and amphetamine-regulated transcript, and inhibition of orexigenic peptides, e.g., neuropeptide Y and agouti-related peptide. Obesity is characterized by hyperleptinemia and hypothalamic leptin resistance, partly caused by induction of suppressor of cytokine signaling-3. Leptin falls rapidly during fasting and potently stimulates appetite, reduces thermogenesis, and mediates the inhibition of thyroid and reproductive hormones and activation of the hypothalamic-pituitary-adrenal axis. These actions are integrated by the paraventicular hypothalamic nucleus. Leptin also decreases glucose and stimulates lipolysis through central and peripheral pathways involving AMP-activated protein kinase (AMPK). Adiponectin is secreted exclusively by adipocytes and has been linked to glucose, lipid, and cardiovascular regulation. Obesity, diabetes, and atherosclerosis have been associated with reduced adiponectin levels, whereas adiponectin treatment reverses these abnormalities partly through activation of AMPK in liver and muscle. Administration of adiponectin in the brain recapitulates the peripheral actions to increase fatty acid oxidation and insulin sensitivity and reduce glucose. Although putative adiponectin receptors are widespread in peripheral organs and brain, it is uncertain whether adiponectin acts exclusively through these targets. As with leptin, adiponectin requires the central melanocortin pathway

  19. Melanocortin receptor-mediated effects on obesity are distributed over specific hypothalamic regions.

    Science.gov (United States)

    de Backer, M W A; la Fleur, S E; Brans, M A D; van Rozen, A J; Luijendijk, M C M; Merkestein, M; Garner, K M; van der Zwaal, E M; Adan, R A H

    2011-05-01

    Reduction of melanocortin signaling in the brain results in obesity. However, where in the brain reduced melanocortin signaling mediates this effect is poorly understood. We determined the effects of long-term inhibition of melanocortin receptor activity in specific brain regions of the rat brain. Melanocortin signaling was inhibited by injection of a recombinant adeno-associated viral (rAAV) vector that overexpressed Agouti-related peptide (AgRP) into the paraventricular nucleus (PVN), the ventromedial hypothalamus (VMH), the lateral hypothalamus (LH) or the accumbens shell (Acc). Overexpression of AgRP in the rat PVN, VMH or LH increased bodyweight, the percentage of white adipose tissue, plasma leptin and insulin concentrations and food intake. Food intake was mainly increased because of an increase in meal size in the light and dark phases, after overexpression of AgRP in the PVN, LH or VMH. Overexpression of AgRP in the PVN or VMH reduced average body core temperature in the dark on day 40 post injection, whereas AgRP overexpression in the LH did not affect temperature. In addition, overexpression of AgRP in the PVN, LH or VMH did not significantly alter mRNA expression of AgRP, neuropeptide Y (NPY), pro-opiomelanocortin (POMC) or suppressor of cytokine signaling 3 (SOCS3) in the arcuate. Overexpression of AgRP in the Acc did not have any effect on the measured parameters. Reduction of melanocortin signaling in several hypothalamic regions increased meal size. However, there were brain area-specific effects on other parameters such as core temperature and plasma leptin concentrations. In a previous study, where NPY was overexpressed with an rAAV vector in the PVN and LH, meal frequency and meal size were increased respectively, whereas locomotor activity was reduced by NPY overexpression at both nuclei. Taken together, AgRP and NPY have complementary roles in energy balance.

  20. Central Sirt1 regulates body weight and energy expenditure along with the POMC-derived peptide α-MSH and the processing enzyme CPE production in diet-induced obese male rats.

    Science.gov (United States)

    Cyr, Nicole E; Steger, Jennifer S; Toorie, Anika M; Yang, Jonathan Z; Stuart, Ronald; Nillni, Eduardo A

    2014-07-01

    In the periphery, the nutrient-sensing enzyme Sirtuin 1 (silent mating type information regulation 2 homolog 1 [Sirt1]) reduces body weight in diet-induced obese (DIO) rodents. However, the role of Sirt1 in the brain, particularly the hypothalamus, in body weight and energy balance regulation is debated. Among the first studies to reveal that central Sirt1 regulates body weight came from experiments in our laboratory using Sprague Dawley rats. In that study, central inhibition of Sirt1 decreased body weight and food intake as a result of a Forkhead box protein O1 (FoxO1)-mediated increase in the anorexigenic proopiomelanocortin (POMC) and decrease in the orexigenic Agouti-related peptide in the hypothalamic arcuate nucleus. Here, we demonstrate that central inhibition of Sirt1 in DIO decreased body weight and increased energy expenditure at higher levels as compared with the lean counterpart. Brain Sirt1 inhibition in DIO increased acetylated FoxO1, which, in turn, increased phosphorylated FoxO1 via improved insulin/pAKT signaling. Elevated acetylated FoxO1 and phosphorylated FoxO1 increased POMC along with the α-MSH maturation enzyme carboxypeptidase E, which resulted in more of the bioactive POMC product α-MSH released into the paraventricular nucleus. Increased in α-MSH led to augmented TRH levels and circulating T3 levels (thyroid hormone). These results indicate that inhibiting hypothalamic Sirt1 in DIO enhances the activity of the hypothalamic-pituitary-thyroid axis, which stimulates energy expenditure. Because we show that blocking central Sirt1 causes physiological changes that promote a negative energy balance in an obese individual, our results support brain Sirt1 as a significant target for weight loss therapeutics.

  1. Identification and characterization of melanocortin-4 receptor gene mutations in morbidly obese finnish children and adults.

    Science.gov (United States)

    Valli-Jaakola, Kaisa; Lipsanen-Nyman, Marita; Oksanen, Laura; Hollenberg, Anthony N; Kontula, Kimmo; Bjørbaek, Christian; Schalin-Jäntti, Camilla

    2004-02-01

    Two Finnish cohorts, comprising 56 children with severe early-onset obesity (relative weight for height greater than or equal to +70% before age 10) and 252 morbidly obese adults (body mass index, > or = 40 kg/m(2)), were screened for melanocortin-4 receptor (MC4R) mutations. We identified a pathogenic mutation (S127L) in one child, causing severe early-onset obesity. We describe the phenotype of this particular mutation for the first time. We also identified a novel (I226T) polymorphism in the coding and two new variations (-439delGC and 1059C>T) outside the coding region of the MC4R gene. Three previously described polymorphisms (V103I, T112M, and I125L) were identified. In vitro functional studies of variants T112M, S127L, and I226T supported a pathogenic role of the S127L mutation, because signaling properties of the receptor in response to the MC4R agonists alpha-MSH, beta-MSH, and gamma(1)-MSH were impaired. The S127L mutation did not affect receptor inhibition by the antagonist agouti-related protein. Localization of the three variant receptors was similar to that of wild type. In conclusion, a pathogenic MC4R mutation was found among subjects with severe early-onset obesity but not among morbidly obese adults. Impaired function of the S127L receptor was due to reduced activation, not a defect of protein transport to the cell membrane.

  2. Linoleic acid and stearic acid elicit opposite effects on AgRP expression and secretion via TLR4-dependent signaling pathways in immortalized hypothalamic N38 cells.

    Science.gov (United States)

    Wang, Songbo; Xiang, Nana; Yang, Liusong; Zhu, Canjun; Zhu, Xiaotong; Wang, Lina; Gao, Ping; Xi, Qianyun; Zhang, Yongliang; Shu, Gang; Jiang, Qingyan

    2016-03-18

    The regulation of food intake is a promising way to combat obesity. It has been implicated that various fatty acids exert different effects on food intake and body weight. However, the underlying mechanism remains poorly understood. The aim of the present study was to investigate the effects of linoleic acid (LA) and stearic acid (SA) on agouti-related protein (AgRP) expression and secretion in immortalized mouse hypothalamic N38 cells and to explore the likely underlying mechanisms. Our results demonstrated that LA inhibited, while SA stimulated AgRP expression and secretion of N38 cells in a dose-dependent manner. In addition, LA suppressed the protein expression of toll-like receptor 4 (TLR4), phosphorylation levels of JNK and IKKα/β, suggesting the inhibition of TLR4-dependent inflammation pathway. However, the above mentioned inhibitory effects of LA were eliminated by TLR4 agonist lipopolysaccharide (LPS). In contrast, SA promoted TLR4 protein expression and activated TLR4-dependent inflammation pathway, with elevated ratio of p-JNK/JNK. While TLR4 siRNA reversed the stimulatory effects of SA on AgRP expression and TLR4-dependent inflammation. Moreover, we found that TLR4 was also involved in LA-enhanced and SA-impaired leptin/insulin signal pathways in N38 cells. In conclusion, our findings indicated that LA elicited inhibitory while SA exerted stimulatory effects on AgRP expression and secretion via TLR4-dependent inflammation and leptin/insulin pathways in N38 cells. These data provided a better understanding of the mechanism underlying fatty acids-regulated food intake and suggested the potential role of long-chain unsaturated fatty acids such as LA in reducing food intake and treating obesity. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Carbenoxolone treatment attenuates symptoms of metabolic syndrome and atherogenesis in obese, hyperlipidemic mice.

    Science.gov (United States)

    Nuotio-Antar, Alli M; Hachey, David L; Hasty, Alyssa H

    2007-12-01

    Glucocorticoids, which are well established to regulate body fat mass distribution, adipocyte lipolysis, hepatic gluconeogenesis, and hepatocyte VLDL secretion, are speculated to play a role in the pathology of metabolic syndrome. Recent focus has been on the activity of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), which is capable of regenerating, and thus amplifying, glucocorticoids in key metabolic tissues such as liver and adipose tissue. To determine the effects of global 11beta-HSD1 inhibition on metabolic syndrome risk factors, we subcutaneously injected "Western"-type diet-fed hyperlipidemic mice displaying moderate or severe obesity [LDL receptor (LDLR)-deficient (LDLR(-/-)) mice and mice derived from heterozygous agouti (A(y)/a) and homozygous LDLR(-/-) breeding pairs (A(y)/a;LDLR(-/-) mice)] with the nonselective 11beta-HSD inhibitor carbenoxolone for 4 wk. Body composition throughout the study, end-point fasting plasma, and extent of hepatic steatosis and atherosclerosis were assessed. This route of treatment led to detection of high levels of carbenoxolone in liver and fat and resulted in decreased weight gain due to reduced body fat mass in both mouse models. However, only A(y)/a;LDLR(-/-) mice showed an effect of 11beta-HSD1 inhibition on fasting insulin and plasma lipids, coincident with a reduction in VLDL due to mildly increased VLDL clearance and dramatically decreased hepatic triglyceride production. A(y)/a;LDLR(-/-) mice also showed a greater effect of the drug on reducing atherosclerotic lesion formation. These findings indicate that subcutaneous injection of an 11beta-HSD1 inhibitor allows for the targeting of the enzyme in not only liver, but also adipose tissue, and attenuates many metabolic syndrome risk factors, with more pronounced effects in cases of severe obesity and hyperlipidemia.

  4. Mahogany (1377-1428) enters brain by a saturable transport system.

    Science.gov (United States)

    Kastin, A J; Akerstrom, V

    2000-08-01

    The mouse mahogany gene encodes a protein that is involved in the suppression of diet-induced obesity. We studied the ability of its widely conserved C-terminal fragment to cross the blood-brain barrier (BBB) in mice. Multiple-time regression analysis showed that the entry rate (K(i)) of (125)I-mahogany (1377-1428) from blood-to-brain was 5.5 x 10(-4) ml/g. min. After coinjection of unlabeled mahogany (1377-1428), the K(i) was significantly decreased, showing the self-inhibition characteristic of a saturable transport mechanism. The excess mahogany (1377-1428) did not change the influx rate of (99m)Tcalbumin, the vascular control, indicating a lack of disruption of the BBB. Statistically significant cross-inhibition was not seen with agouti-related protein (83-132), melanin-concentrating hormone, epidermal growth factor, leptin, a melanocortin-4 receptor antagonist, or alpha-melanocyte-stimulating hormone. HPLC showed that most of the injected (125)I-mahogany (1377-1428) reached the brain intact, and capillary depletion with washout showed that most of it reached the parenchyma. There was no brain-to-blood efflux system for mahogany (1377-1428) but rather retention after i.c.v. administration, and the octanol/buffer partition coefficient showed low lipophilicity. Thus, the results show that the C-terminal peptide product encoded by the mahogany gene crosses the BBB by a transport mechanism that is saturable. The ability of this system to be regulated indicates the therapeutic potential of mahogany (1377-1428) in the treatment of obesity.

  5. Preserved energy balance in mice lacking FoxO1 in neurons of Nkx2.1 lineage reveals functional heterogeneity of FoxO1 signaling within the hypothalamus.

    Science.gov (United States)

    Heinrich, Garrett; Meece, Kana; Wardlaw, Sharon L; Accili, Domenico

    2014-05-01

    Transcription factor forkhead box O1 (FoxO1) regulates energy expenditure (EE), food intake, and hepatic glucose production. These activities have been mapped to specific hypothalamic neuronal populations using cell type-specific knockout experiments in mice. To parse out the integrated output of FoxO1-dependent transcription from different neuronal populations and multiple hypothalamic regions, we used transgenic mice expressing Cre recombinase from the Nkx2.1 promoter to ablate loxP-flanked Foxo1 alleles from a majority of hypothalamic neurons (Foxo1KO(Nkx2.1) mice). This strategy resulted in the expected inhibition of FoxO1 expression, but only produced a transient reduction of body weight as well as a decreased body length. The transient decrease of body weight in male mice was accompanied by decreased fat mass. Male Foxo1KO(Nkx2.1) mice show food intake similar to that in wild-type controls, and, although female knockout mice eat less, they do so in proportion to a reduced body size. EE is unaffected in Foxo1KO(Nkx2.1) mice, although small increases in body temperature are present. Unlike other neuron-specific Foxo1 knockout mice, Foxo1KO(Nkx2.1) mice are not protected from diet-induced obesity. These studies indicate that, unlike the metabolic effects of highly restricted neuronal subsets (proopiomelanocortin, neuropeptide Y/agouti-related peptide, and steroidogenic factor 1), those of neurons derived from the Nkx2.1 lineage either occur in a FoxO1-independent fashion or are compensated for through developmental plasticity.

  6. A spermine-coupled cholesterol metabolite from the shark with potent appetite suppressant and antidiabetic properties.

    Science.gov (United States)

    Zasloff, M; Williams, J I; Chen, Q; Anderson, M; Maeder, T; Holroyd, K; Jones, S; Kinney, W; Cheshire, K; McLane, M

    2001-05-01

    We describe the pharmacological properties of a novel spermine-cholesterol adduct, MSI 1436 (3beta-N-1(spermine)-7alpha, 24R-dihydroxy-5alpha-cholestane 24-sulfate), which causes reversible suppression of food and fluid intake in mammals resulting in profound weight loss, not associated with other signs or symptoms of illness, and which exhibits antidiabetic properties in genetically obese mice. Wild-type rodents and strains with genetic obesity were studied. Effects on food and fluid intake, body weight and composition were examined along with pharmacological and toxicological parameters. MSI-1436 induces profound inhibition of food and fluid intake in rats and mice, resulting in significant weight loss. MSI-1436 is active when introduced directly into the third ventricle of the rat, suggesting the compound acts on central targets. Pair-feeding studies suggest that MSI-1436 causes weight loss by suppressing food intake. Fluid intake is also profoundly reduced but animals remain normally hydrated and defend both water and electrolyte balance from parenteral administration. MSI-1436 is active in ob/ob, db/db, agouti and MC4 receptor knockout mice. MSI-1436 has been administered to ob/ob mice over a 4 month period via a regimen that safely controls body weight, glucose homeostasis and serum cholesterol levels. Following MSI-1436 treatment, db/db mice preferentially mobilize adipose tissue and hyperglycemia is corrected. A naturally occurring spermine metabolite of cholesterol, isolated from the dogfish shark, Squalus acanthias, has been identified that induces profound reduction in food and fluid intake in rodents in a setting where thirst is preserved and fluid and electrolyte homeostasis appears to be functioning normally. MSI-1436 probably acts on a central target involving neural circuits that lie downstream from the leptin and the MC4 receptors. Although long-term administration can be accomplished safely in mice, the utility of this compound as a potential

  7. Effects of vaspin, chemerin and omentin-1 on feeding behavior and hypothalamic peptide gene expression in the rat.

    Science.gov (United States)

    Brunetti, Luigi; Di Nisio, Chiara; Recinella, Lucia; Chiavaroli, Annalisa; Leone, Sheila; Ferrante, Claudio; Orlando, Giustino; Vacca, Michele

    2011-09-01

    Visceral adipose tissue-derived serpin (vaspin) improves glucose tolerance and insulin sensitivity in diet-induced obese mice. Chemerin may increase insulin sensitivity in adipose tissue and seems to be associated with several key aspects of metabolic syndrome. Decreased levels of omentin-1 are associated with increasing obesity and insulin resistance. Our study aimed to investigate the effects of vaspin, chemerin and omentin-1 acute administration on feeding and hypothalamic gene expression of peptides which play a key role in feeding regulation. 35 rats were injected into the arcuate nucleus (ARC) of the hypothalamus with either saline (n=8), vaspin (1μg/kg; n=9), chemerin (8μg/kg; n=9), or omentin-1 (8μg/kg; n=9). Food intake in the following 24h was recorded, thereafter rats were sacrificed. Total RNA was extracted from hypothalami and reverse transcribed to evaluate hypothalamic gene expression of agouti-related peptide (AgRP), neuropeptide Y (NPY), orexin-A, cocaine- and amphetamine-regulated transcript (CART), corticotrophin releasing hormone (CRH) and proopiomelanocortin (POMC), by real-time reverse transcription polymerase chain reaction. Compared to vehicle, vaspin injection significantly decreased feeding, while chemerin and omentin-1 had no effect in the tested dose. Vaspin treatment significantly decreased NPY and increased POMC gene expression. Chemerin treatment led to a significant increase of both AgRP and POMC gene expression. Omentin-1 treatment did not modify gene expression of the investigated peptides. Therefore, vaspin is an adipokine triggering anorectic pathways in the hypothalamus, where reduction of NPY and increase of POMC mRNA levels mediate feeding inhibition. Chemerin and omentin-1 have no effect on feeding in the tested dose. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Central orchestration of peripheral nutrient partitioning and substrate utilization: implications for the metabolic syndrome.

    Science.gov (United States)

    Denis, R G P; Joly-Amado, A; Cansell, C; Castel, J; Martinez, S; Delbes, A S; Luquet, S

    2014-06-01

    Energy homoeostasis is maintained through a complex interplay of nutrient intake and energy expenditure. The central nervous system is an essential component of this regulation, as it integrates circulating signals of hunger and satiety to develop adaptive responses at the behavioural and metabolic levels, while the hypothalamus is regarded as a particularly crucial structure in the brain in terms of energy homoeostasis. The arcuate nucleus (ARC) of the hypothalamus contains at least two intermingled neuronal populations: the neurons that produce neuropeptide Y (NPY); and the Agouti-related protein (AgRP) produced by AgRP/NPY neurons situated below the third ventricle in close proximity to proopiomelanocortin (POMC)-producing neurons. POMC neurons exert their catabolic and anorectic actions by releasing α-melanocyte-stimulating hormone (α-MSH), while AgRP neurons oppose this action by exerting tonic GABAergic inhibition of POMC neurons and releasing the melanocortin receptor inverse agonist AgRP. The release of neurotransmitters and neuropeptides by second-order AgRP neurons appears to take place on a multiple time scale, thereby allowing neuromodulation of preganglionic neuronal activity and subsequent control of nutrient partitioning - in other words, the coordinated regulation of conversion, storage and utilization of carbohydrates vs. lipids. This suggests that the function of AgRP neurons extends beyond the strict regulation of feeding to the regulation of efferent organ activity, such that AgRP neurons may now be viewed as an important bridge between central detection of nutrient availability and peripheral nutrient partitioning, thus providing a mechanistic link between obesity and obesity-related disorders. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  9. Fish melanocortin system.

    Science.gov (United States)

    Cerdá-Reverter, José Miguel; Agulleiro, Maria Josep; R, Raúl Guillot; Sánchez, Elisa; Ceinos, Rosa; Rotllant, Josep

    2011-06-11

    Melanocortin signalling is mediated by binding to a family of G protein-coupled receptors that positively couple to adenylyl cyclase. Tetrapod species have five melanocortin (MC(1)-MC(5)) receptors. The number of receptors varies in fish, zebrafish, for example, having six melanocortin receptors, with two copies of the melanocortin MC(5) receptor, while pufferfish have 4 receptors with no melanocortin MC(3) receptor and one copy of melanocortin MC(5) receptor. Fish genomes also exhibit orthologue genes for agouti-signalling protein (ASP) and -related protein (AGRP). AGRP expression is confined to a small area in the hypothalamus but ASP is expressed in the skin. Fish melanocortin MC(2) receptor is specific for ACTH and requires the cooperation of accessory proteins (MRAP) to reach functional expression. The four other melanocortin MC receptors distinctively bind MSHs. The interaction of α-MSH and melanocortin MC(1) receptor plays a key point in the control of the pigmentation and mutations of melanocortin MC(1) receptor are responsible for reduced melanization. Both melanocortin MC(4) and MC(5) receptor are expressed in the hypothalamus, and central melanocortin MC(4) receptor expression is thought to regulate the energy balance through the modulation of feeding behaviour. In addition, the peripheral melanocortin system also regulates lipid metabolism by acting at hepatic melanocortin MC(2) and MC(5) receptors. Both sea bass melanocortin MC(1) and MC(4) receptors are constitutively expressed in vitro and both ASP and AGRP work as inverse agonists but only after inhibition of the phosphodiesterase system. Accordingly, the overexpression of AGRP and ASP transgenes promotes obesity and reduces melanization in zebrafish, respectively. Copyright © 2010 Elsevier B.V. All rights reserved.

  10. Disproportionate inhibition of feeding in A(y) mice by certain stressors: a cautionary note.

    Science.gov (United States)

    De Souza, J; Butler, A A; Cone, R D

    2000-08-01

    A study of the effects of insulin-induced hypoglycemia in the obese yellow agouti A(y) mouse was initiated to test the hypothesis that the central melanocortin pathways are required for a normal sympathetic response to hypoglycemia. An experimental protocol was performed in which young nonobese male mice were isolated and fasted beginning on day 1, then tested for glucose responses to insulin-induced hypoglycemia on day 2. Normal mice demonstrated the expected glucose rebound to hypoglycemia, exceeding baseline glucose levels by 2-3 times as a consequence of increased gluconeogenesis and glycogenolysis before returning to baseline levels. A(y) animals lacked the rebound, exhibiting instead a gradual restoration of baseline glucose levels. The results suggested a defective sympathetic response to hypoglycemia in the A(y) mouse. However, a more detailed analysis demonstrated that the lack of a hyperglycemic rebound was due to an acute inhibition of feeding specifically in the A(y) mouse, which resulted not from the hypoglycemia stressor, but rather from the stress of isolation. Handling and intraperitoneal administration of saline also specifically inhibited food intake in the A(y) but not the wild-type mouse, while restraint stress had an equivalent inhibitory effect on food intake on wild-type and A(y) mice. Since the A(y) mouse has defective hypothalamic melanocortin-4 receptor (MC4-R) signaling, these data imply that the central melanocortin pathway is necessary for regulating the effects of stress on feeding behavior. Furthermore, these data demonstrate the need for exercising extreme caution in designing experiments to analyze feeding behavior and metabolism in genetic or pharmacological models involving perturbation of the melanocortin system. Copyright 2000 S. Karger AG, Basel.

  11. Direct and indirect effects of cannabinoids on in vitro GABA release in the rat arcuate nucleus.

    Science.gov (United States)

    Menzies, J R W; Ludwig, M; Leng, G

    2010-06-01

    Within the hypothalamic arcuate nucleus, two neuronal subpopulations play particularly important roles in energy balance; neurones expressing neuropeptide Y (NPY), agouti-related peptide (AgRP) and GABA are orexigenic, whereas neurones expressing pro-opiomelanocortin and CART are anorexigenic. The pivotal role of these neuropeptides in energy homeostasis is well-known, although GABA may also be an important signal because targeted knockout of the GABA transporter in NPY/AgRP/GABA neurones results in a lean, obesity-resistant phenotype. In the present study, we describe an in vitro model of K(+)-evoked GABA release from the hypothalamus and determine the effects of cannabinoid receptor activation. K(+)-evoked GABA release was sensitive to leptin, insulin and PYY(3-36), indicating that GABA was released by arcuate NPY/AgRP/GABA neurones. In the presence of tetrodotoxin (TTX), the cannabinoid CB1 receptor agonist WIN 55,212-2 inhibited K(+)-evoked GABA release. This was prevented by the CB1 receptor inverse agonist rimonabant. Rimonabant had no effect when applied alone. In the absence of TTX, however, the opposite effects were observed: WIN 55,212-2 had no effect while rimonabant inhibited GABA release. This indicates that GABA release can involve an indirect, TTX-sensitive mechanism. The most parsimonious explanation for the inhibition of GABA release by a CB receptor inverse agonist is via the disinhibition of an cannabinoid-sensitive inhibitory input onto GABAergic neurones. One local source of an inhibitory neurotransmitter is the opioidergic arcuate neurones. In our in vitro model, K(+)-evoked GABA release was inhibited by the endogenous opioid peptide beta-endorphin in a naloxone-sensitive manner. The inhibitory effect of rimonabant was also prevented by naloxone and a kappa-opioid receptor selective antagonist, suggesting that GABA release from arcuate NPY/AgRP/GABA neurones can be inhibited by endogenous opioid peptides, and that the release of opioid

  12. Central Sirt1 regulates body weight and energy expenditure along with the POMC-derived peptide α-MSH and the processing enzyme CPE production in diet-induced obese male rats.

    Science.gov (United States)

    Cyr, Nicole E; Steger, Jennifer S; Toorie, Anika M; Yang, Jonathan Z; Stuart, Ronald; Nillni, Eduardo A

    2015-03-01

    In the periphery, the nutrient-sensing enzyme Sirtuin 1 (silent mating type information regulation 2 homolog 1 [Sirt1]) reduces body weight in diet-induced obese (DIO) rodents. However, the role of hypothalamic Sirt1 in body weight and energy balance regulation is debated. The first studies to reveal that central Sirt1 regulates body weight came from experiments in our laboratory using Sprague-Dawley rats. Central inhibition of Sirt1 decreased body weight and food intake as a result of a forkhead box protein O1 (FoxO1)-mediated increase in the anorexigenic proopiomelanocortin (POMC) and decrease in the orexigenic Agouti-related peptide in the hypothalamic arcuate nucleus. Here, we demonstrate that central inhibition of Sirt1 in DIO decreased body weight and increased energy expenditure at higher levels as compared with the lean counterpart. Brain Sirt1 inhibition in DIO increased acetylated FoxO1, which in turn increased phosphorylated FoxO1 via improved insulin/phosphorylated AKT signaling. Elevated acetylated FoxO1 and phosphorylated FoxO1 increased POMC along with the α-melanocyte-stimulating hormone (α-MSH) maturation enzyme carboxypeptidase E, which resulted in more of the bioactive POMC product α-MSH released into the paraventricular nucleus. Increased in α-MSH led to augmented TRH levels and circulating T3 levels (triiodothyronine, thyroid hormone). These results indicate that inhibiting hypothalamic Sirt1 in DIO enhances the activity of the hypothalamic-pituitary-thyroid axis, which stimulates energy expenditure. Because we show that blocking central Sirt1 causes physiological changes that promote a negative energy balance in an obese individual, our results support brain Sirt1 as a significant target for weight loss therapeutics.

  13. High ambient temperature reverses hypothalamic MC4 receptor overexpression in an animal model of anorexia nervosa.

    Science.gov (United States)

    Gutiérrez, E; Churruca, I; Zárate, J; Carrera, O; Portillo, M P; Cerrato, M; Vázquez, R; Echevarría, E

    2009-04-01

    The potential involvement of the melanocortin system in the beneficial effects of heat application in rats submitted to activity-based anorexia (ABA), an analogous model of anorexia nervosa (AN), was studied. Once ABA rats had lost 20% of body weight, half of the animals were exposed to a high ambient temperature (HAT) of 32 degrees C, whereas the rest were maintained at 21 degrees C. Control sedentary rats yoked to ABA animals received the same treatment. ABA rats (21 degrees C) showed increased Melanocortin 4 (MC4) receptor and Agouti gene Related Peptide (AgRP) expression, and decreased pro-opiomelanocortin (POMC) mRNA levels (Real Time PCR), with respect to controls. Heat application increased weight gain and food intake, and reduced running rate in ABA rats, when compared with ABA rats at 21 degrees C. However, no changes in body weight and food intake were observed in sedentary rats exposed to heat. Moreover, heat application reduced MC4 receptor, AgRP and POMC expression in ABA rats, but no changes were observed in control rats. These results indicate that hypothalamic MC4 receptor overexpression could occur on the basis of the characteristic hyperactivity, weight loss, and self-starvation of ABA rats, and suggest the involvement of hypothalamic melanocortin neural circuits in behavioural changes shown by AN patients. Changes in AgRP and POMC expression could represent an adaptative response to equilibrate energy balance. Moreover, the fact that HAT reversed hypothalamic MC4 receptor overexpression in ABA rats indicates the involvement of brain melanocortin system in the reported beneficial effects of heat application in AN. A combination of MC4 receptor antagonists and heat application could improve the clinical management of AN.

  14. Impact of hypothalamic reactive oxygen species in the regulation of energy metabolism and food intake.

    Science.gov (United States)

    Drougard, Anne; Fournel, Audren; Valet, Philippe; Knauf, Claude

    2015-01-01

    Hypothalamus is a key area involved in the control of metabolism and food intake via the integrations of numerous signals (hormones, neurotransmitters, metabolites) from various origins. These factors modify hypothalamic neurons activity and generate adequate molecular and behavioral responses to control energy balance. In this complex integrative system, a new concept has been developed in recent years, that includes reactive oxygen species (ROS) as a critical player in energy balance. ROS are known to act in many signaling pathways in different peripheral organs, but also in hypothalamus where they regulate food intake and metabolism by acting on different types of neurons, including proopiomelanocortin (POMC) and agouti-related protein (AgRP)/neuropeptide Y (NPY) neurons. Hypothalamic ROS release is under the influence of different factors such as pancreatic and gut hormones, adipokines (leptin, apelin,…), neurotransmitters and nutrients (glucose, lipids,…). The sources of ROS production are multiple including NADPH oxidase, but also the mitochondria which is considered as the main ROS producer in the brain. ROS are considered as signaling molecules, but conversely impairment of this neuronal signaling ROS pathway contributes to alterations of autonomic nervous system and neuroendocrine function, leading to metabolic diseases such as obesity and type 2 diabetes. In this review we focus our attention on factors that are able to modulate hypothalamic ROS release in order to control food intake and energy metabolism, and whose deregulations could participate to the development of pathological conditions. This novel insight reveals an original mechanism in the hypothalamus that controls energy balance and identify hypothalamic ROS signaling as a potential therapeutic strategy to treat metabolic disorders.

  15. Expression levels of genes encoding melanin concentrating hormone (MCH) and MCH receptor change in taste aversion, but MCH injections do not alleviate aversive responses.

    Science.gov (United States)

    Mitra, Anaya; Klockars, Anica; Gosnell, Blake A; Le Grevès, Madeleine; Olszewski, Pawel K; Levine, Allen S; Schiöth, Helgi B

    2012-01-01

    Melanin concentrating hormone (MCH) stimulates feeding driven by energy needs and reward and modifies anxiety behavior. Orexigenic peptides of similar characteristics, including nociceptin/orphanin FQ, Agouti-related protein and opioids, increase consumption also by reducing avoidance of potentially tainted food in animals displaying a conditioned taste aversion (CTA). Herein, using real-time PCR, we assessed whether expression levels of genes encoding MCH and its receptor, MCHR1, were affected in CTA in the rat. We also investigated whether injecting MCH intracerebroventricularly (ICV) during the acquisition and retrieval of LiCl-induced CTA, would alleviate aversive responses. MCHR1 gene was upregulated in the hypothalamus and brain stem of aversive animals, MCH mRNA was significantly higher in the hypothalamus, whereas a strong trend suggesting upregulation of MCH and MCHR1 genes was detected in the amygdala. Despite these expression changes associated with aversion, MCH injected prior to the induction of CTA with LiCl as well as later, during the CTA retrieval upon subsequent presentations of the aversive tastant, did not reduce the magnitude of CTA. We conclude that MCH and its receptor form an orexigenic system whose expression is affected in CTA. This altered MCH expression may contribute to tastant-targeted hypophagia in CTA. However, changing the MCH tone in the brain by exogenous peptide was insufficient to prevent the onset or facilitate extinction of LiCl-induced CTA. This designates MCH as one of many accessory molecules associated with shaping an aversive response, but not a critical one for LiCl-dependent CTA to occur. Published by Elsevier Inc.

  16. Not another type of potato: MC1R and the russet coloration of Burmese cats.

    Science.gov (United States)

    Gustafson, N A; Gandolfi, B; Lyons, L A

    2017-02-01

    The Burmese is a breed of domestic cat that originated in Southeast Asia and was further developed in the United States. Variants in melanocortin 1 receptor (MC1R) causes common coat colour phenotypes in a variety of mammalian species but only limited colour variation in the domestic cat. Known as the extension (E) locus, melanocortin 1 receptor (MC1R) interacts with the agouti locus to produce the eumelanin and pheomelanin pigments. Recently, a novel reddish coloration, which is termed russet, was identified in the Burmese cat breed. Because this russet Burmese coloration changes with aging, MC1R was suggested as candidate gene. The similar colouration in specific lineages of Norwegian Forest cat known as amber (e) (c.250G>A; p.Asp84Asn) was excluded for this Burmese phenotype. The complete 954-bp coding region of MC1R was directly sequenced in russet Burmese and suspected carriers. A 3-bp deletion (c.439_441del) associated with the deletion of a phenyalanine (p.Phe146del) in the protein sequence was identified. All russet coloured cats were homozygous for the variant, and all obligate carriers were heterozygous, confirming that the deletion segregated concordantly with colouring in Burmese cats from the New Zealand foundation lineage. The variant was not identified in 442 cats from 26 different breeds and random-bred cats. Twenty-six Burmese from the USA did not have the variant. This MC1R variant defines a unique coloration and the second breed-specific MC1R variant in cats. The interactions of the two recessive feline MC1R alleles (E  >  e, er ) is unknown. © 2016 Stichting International Foundation for Animal Genetics.

  17. Inherited variation at MC1R and ASIP and association with melanoma-specific survival.

    Science.gov (United States)

    Taylor, Nicholas J; Reiner, Anne S; Begg, Colin B; Cust, Anne E; Busam, Klaus J; Anton-Culver, Hoda; Dwyer, Terence; From, Lynn; Gallagher, Richard P; Gruber, Stephen B; Rosso, Stefano; White, Kirsten A; Zanetti, Roberto; Orlow, Irene; Thomas, Nancy E; Rebbeck, Timothy R; Berwick, Marianne; Kanetsky, Peter A

    2015-06-01

    Melanocortin-1 receptor (MC1R) is a marker of melanoma risk in populations of European ancestry. However, MC1R effects on survival are much less studied. We investigated associations between variation at MC1R and survival in an international, population-based series of single primary melanoma patients enrolled into the Genes, Environment, and Melanoma study. MC1R genotype data was available for 2,200 participants with a first incident primary melanoma diagnosis. We estimated the association of MC1R genotypes with melanoma-specific survival (i.e., death caused by melanoma) and overall survival using COX proportional hazards modeling, adjusting for established prognostic factors for melanoma. We also conducted stratified analyses by Breslow thickness, tumor site, phenotypic index, and age. In addition, we evaluated haplotypes involving polymorphisms near the Agouti signaling protein gene (ASIP) locus for their impacts on survival. Melanoma-specific survival was inversely associated with carriage of MC1R variants in the absence of consensus alleles compared to carriage of at least one consensus allele (hazard ratio (HR) = 0.60; 95% confidence interval (CI): 0.40, 0.90). MC1R results for overall survival were consistent with no association. We did not observe any statistical evidence of heterogeneity of effect estimates in stratified analyses. We observed increased hazard of melanoma-specific death among carriers of the risk haplotype TG near the ASIP locus (HR = 1.37; 95% CI: 0.91, 2.04) when compared to carriers of the most common GG haplotype. Similar results were noted for overall survival. Upon examining the ASIP TG/TG diplotype, we observed considerably increased hazard of melanoma-specific death (HR = 5.11; 95% CI: 1.88, 13.88) compared to carriers of the most common GG/GG diplotype. Our data suggest improved melanoma-specific survival among carriers of two inherited MC1R variants. © 2014 UICC.

  18. Coat colour phenotype of Qingyu pig is associated with polymorphisms of melanocortin receptor 1 gene

    Directory of Open Access Journals (Sweden)

    Xiaoqian Wu

    2017-07-01

    Full Text Available Objective Qingyu pig, a Chinese indigenous pig breed, exhibits two types of coat colour phenotypes, including pure black and white with black spotting respectively. Melanocortin receptor 1 (MC1R and agouti signaling protein (ASIP are two widely reported pivotal genes that significantly affect the regulation of coat colour. The objectives of this study were to investigate whether the polymorphisms of these two genes are associated with coat colour and analyze the molecular mechanism of the coat colour separation in Qingyu pig. Methods We studied the phenotype segregation and used polymerase chain reaction amplification and Sanger sequencing to investigate the polymorphism of MC1R and ASIP in 121 Qingyu pigs, consisting of 115 black and 6 white with black spotted pigs. Results Coat colour of Qingyu pig is associated with the polymorphisms of MC1R but not ASIP. We only found 2 haplotypes, EQY and Eqy, based on the 13 observed mutations from MC1R gene. Among which, Eqy presented a recessive inheritance mode in black spotted Qingyu pigs. Further analysis revealed a g.462–463CC insertion that caused a frameshift mutation and a premature stop codon, thus changed the first transmembrane domain completely and lost the remaining six transmembrane domains. Altogether, our results strongly support that the variety of Qingyu pig’s coat colour is related to MC1R. Conclusion Our findings indicated that black coat colour in Qingyu pig was dominant to white with black spotted phenotype and MC1R gene polymorphism was associated with coat colour separation in Qingyu pig.

  19. The MC1R and ASIP Coat Color Loci May Impact Behavior in the Horse.

    Science.gov (United States)

    Jacobs, Lauren N; Staiger, Elizabeth A; Albright, Julia D; Brooks, Samantha A

    2016-05-01

    Shared signaling pathways utilized by melanocytes and neurons result in pleiotropic traits of coat color and behavior in many mammalian species. For example, in humans polymorphisms at MC1R cause red hair, increased heat sensitivity, and lower pain tolerance. In deer mice, rats, and foxes, ASIP polymorphisms causing black coat color lead to more docile demeanors and reduced activity. Horse (Equus caballus) base coat color is primarily determined by polymorphisms at the Melanocortin-1 Receptor (MC1R) and Agouti Signaling Protein (ASIP) loci, creating a black, bay, or chestnut coat. Our goal was to investigate correlations between genetic loci for coat color and temperament traits in the horse. We genotyped a total of 215 North American Tennessee Walking Horses for the 2 most common alleles at the MC1R (E/e) and ASIP (A/a) loci using previously published PCR and RFLP methods. The horses had a mean age of 10.5 years and comprised 83 geldings, 25 stallions, and 107 mares. To assess behavior, we adapted a previously published survey for handlers to score horses from 1 to 9 on 20 questions related to specific aspects of temperament. We utilized principle component analysis to combine the individual survey scores into 4 factors of variation in temperament phenotype. A factor component detailing self-reliance correlated with genotypes at the ASIP locus; black mares (aa) were more independent than bay mares (A_) (P = 0.0063). These findings illuminate a promising and novel animal model for future study of neuroendocrine mechanisms in complex behavioral phenotypes. © The American Genetic Association. 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. PTP1B deficiency improves hypothalamic insulin sensitivity resulting in the attenuation of AgRP mRNA expression under high-fat diet conditions.

    Science.gov (United States)

    Sugiyama, Mariko; Banno, Ryoichi; Mizoguchi, Akira; Tominaga, Takashi; Tsunekawa, Taku; Onoue, Takeshi; Hagiwara, Daisuke; Ito, Yoshihiro; Morishita, Yoshiaki; Iwama, Shintaro; Goto, Motomitsu; Suga, Hidetaka; Arima, Hiroshi

    2017-06-17

    Hypothalamic insulin receptor signaling regulates energy balance and glucose homeostasis via agouti-related protein (AgRP). While protein tyrosine phosphatase 1B (PTP1B) is classically known to be a negative regulator of peripheral insulin signaling by dephosphorylating both insulin receptor β (IRβ) and insulin receptor substrate, the role of PTP1B in hypothalamic insulin signaling remains to be fully elucidated. In the present study, we investigated the role of PTP1B in hypothalamic insulin signaling using PTP1B deficient (KO) mice in vivo and ex vivo. For the in vivo study, hypothalamic insulin resistance induced by a high-fat diet (HFD) improved in KO mice compared to wild-type (WT) mice. Hypothalamic AgRP mRNA expression levels were also significantly decreased in KO mice independent of body weight changes. In an ex vivo study using hypothalamic organotypic cultures, insulin treatment significantly increased the phosphorylation of both IRβ and Akt in the hypothalamus of KO mice compared to WT mice, and also significantly decreased AgRP mRNA expression levels in KO mice. While incubation with inhibitors of phosphatidylinositol-3 kinase (PI3K) had no effect on basal levels of Akt phosphorylation, these suppressed insulin induction of Akt phosphorylation to almost basal levels in WT and KO mice. The inhibition of the PI3K-Akt pathway blocked the downregulation of AgRP mRNA expression in KO mice treated with insulin. These data suggest that PTP1B acts on the hypothalamic insulin signaling via the PI3K-Akt pathway. Together, our results suggest a deficiency of PTP1B improves hypothalamic insulin sensitivity resulting in the attenuation of AgRP mRNA expression under HFD conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Novel genes on rat chromosome 10 are linked to body fat mass, preadipocyte number and adipocyte size.

    Science.gov (United States)

    Weingarten, A; Turchetti, L; Krohn, K; Klöting, I; Kern, M; Kovacs, P; Stumvoll, M; Blüher, M; Klöting, N

    2016-12-01

    The genetic architecture of obesity is multifactorial. We have previously identified a quantitative trait locus (QTL) on rat chromosome 10 in a F2 cross of Wistar Ottawa Karlsburg (WOKW) and Dark Agouti (DA) rats responsible for obesity-related traits. The QTL was confirmed in congenic DA.WOKW10 rats. To pinpoint the region carrying causal genes, we established two new subcongenic lines, L1 and L2, with smaller refined segments of chromosome 10 to identify novel candidate genes. All lines were extensively characterized under different diet conditions. We employed transcriptome analysis in visceral adipose tissue (VAT) by RNA-Seq technology to identify potential underlying genes in the segregating regions. Three candidate genes were measured in human paired samples of VAT and subcutaneous (SC) AT (SAT) (N=304) individuals with a wide range of body weight and glucose homeostasis parameters. DA.WOKW and L1 subcongenic lines were protected against body fat gain under high-fat diet (HFD), whereas L2 and DA had significantly more body fat after high-fat feeding. Interestingly, adipocyte size distribution in SAT and epigonadal AT of L1 subcongenic rats did not undergo typical ballooning under HFD and the number of preadipocytes in AT was significantly elevated in L2 compared with L1 and parental rats. Transcriptome analysis identified three candidate genes in VAT on rat chromosome 10. In humans, these candidate genes were differentially expressed between SAT and VAT. Moreover, HID1 mRNA significantly correlates with parameters of obesity and glucose metabolism. Our data suggest novel candidate genes for obesity that map on rat chromosome 10 in an interval 102.2-104.7 Mb and are strongly associated with body fat mass regulation, preadipocyte number and adipocyte size in rats. Among those genes, AT head involution defective (HID1) mRNA expression may be relevant for human fat distribution and glucose homeostasis.

  2. Sex Difference in Oxidative Stress Parameters in Spinal Cord of Rats with Experimental Autoimmune Encephalomyelitis: Relation to Neurological Deficit.

    Science.gov (United States)

    Dimitrijević, Mirjana; Kotur-Stevuljević, Jelena; Stojić-Vukanić, Zorica; Vujnović, Ivana; Pilipović, Ivan; Nacka-Aleksić, Mirjana; Leposavić, Gordana

    2017-02-01

    The study examined (a) whether there is sex difference in spinal cord and plasma oxidative stress profiles in Dark Agouti rats immunised for experimental autoimmune encephalomyelitis (EAE), the principal experimental model of multiple sclerosis, and (b) whether there is correlation between the oxidative stress in spinal cord and neurological deficit. Regardless of rat sex, with the disease development xanthine oxidase (XO) activity and inducible nitric oxide synthase (iNOS) mRNA expression increased in spinal cord, whereas glutathione levels decreased. This was accompanied by the rise in spinal cord malondialdehyde level. On the other hand, with EAE development superoxide dismutase (SOD) activity decreased, while O2(-) concentration increased only in spinal cord of male rats. Consequently, SOD activity was lower, whereas O2(-) concentration was higher in spinal cord of male rats with clinically manifested EAE. XO activity and iNOS mRNA expression were also elevated in their spinal cord. Consistently, in the effector phase of EAE the concentration of advanced oxidation protein product (AOPP) was higher in spinal cord of male rats, which exhibit more severe neurological deficit than their female counterparts. In as much as data obtained in the experimental models could be translated to humans, the findings may be relevant for designing sex-specific antioxidant therapeutic strategies. Furthermore, the study indicated that the increased pro-oxidant-antioxidant balance in plasma may be an early indicator of EAE development. Moreover, it showed that plasma AOPP level may indicate not only actual activity of the disease, but also serve to predict severity of its course.

  3. Proliferative Hypothalamic Neurospheres Express NPY, AGRP, POMC, CART and Orexin-A and Differentiate to Functional Neurons

    Science.gov (United States)

    Sousa-Ferreira, Lígia; Álvaro, Ana Rita; Aveleira, Célia; Santana, Magda; Brandão, Inês; Kügler, Sebastian; Pereira de Almeida, Luís; Cavadas, Cláudia

    2011-01-01

    Some pathological conditions with feeding pattern alterations, including obesity and Huntington disease (HD) are associated with hypothalamic dysfunction and neuronal cell death. Additionally, the hypothalamus is a neurogenic region with the constitutive capacity to generate new cells of neuronal lineage, in adult rodents. The aim of the present work was to evaluate the expression of feeding-related neuropeptides in hypothalamic progenitor cells and their capacity to differentiate to functional neurons which have been described to be affected by hypothalamic dysfunction. Our study shows that hypothalamic progenitor cells from rat embryos grow as floating neurospheres and express the feeding-related neuropeptides Neuropeptide Y (NPY), Agouti-related Protein (AGRP), Pro-OpioMelanocortin (POMC), Cocaine-and-Amphetamine Responsive Transcript (CART) and Orexin-A/Hypocretin-1. Moreover the relative mRNA expression of NPY and POMC increases during the expansion of hypothalamic neurospheres in proliferative conditions. Mature neurons were obtained from the differentiation of hypothalamic progenitor cells including NPY, AGRP, POMC, CART and Orexin-A positive neurons. Furthermore the relative mRNA expression of NPY, CART and Orexin-A increases after the differentiation of hypothalamic neurospheres. Similarly to the adult hypothalamic neurons the neurospheres-derived neurons express the glutamat