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Sample records for agouti dasyprocta leporina

  1. Perimortality in a Captive Reared Agouti (Dasyprocta leporina

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    Gary Wayne Garcia

    2015-12-01

    Full Text Available erinatal mortality has been reported in cattle, swine, goats, sheep and rabbits; however, there have been no documented reports on this phenomenon in agouti (Dasyprocta leporina. The agouti is a Neotropical polytocous rodent, hunted for its meat. This study reports on an incident of perinatal mortalities in a captive reared agouti from the wildlife unit of the Faculty of Food and Agriculture. The pluriparous female agouti was reared in captivity from birth and had delivered three (3 previous litters successfully. These ranged from 2-3 young, with a 100% survival rate. This case presented a difficult labor, with delivery of three (3 healthy female precocious offspring (434g, 378g and 402g, and three (3 perinatal mortalities (285g, 368g and 300g. The female agouti died during delivery and postmortem results indicated that Dystocia resulting in Secondary Uterine Inertia as the cause of death. This abnormally large litter may have been as a result of captive conditions, where an abundance of food and a lack of predators may have dulled the animal’s survival instinct. The agouti’s ability and the time taken to deliver all six (6 young may also have contributed to the animals delivery stress.

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

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    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.

  3. 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

    . 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...... of lacunae. Microvilli project into these lacunae from the plasma membrane of the syncytiotrophoblast. The syncytial cytoplasm contains electron-dense granules. This is probably the amylase-resistant PAS-positive material identified by histochemistry. The subplacenta is supplied entirely from the fetal...... circulation. Within it the vessels pursue a tortuous course with sinusoidal dilatations and constrictions. CONCLUSION: The functions that have been attributed to the subplacenta include hormone production. Our findings are consistent with this interpretation, but suggest that hormone secretion is directed...

  4. 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

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    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.

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

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    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.

  6. 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

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    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.

  7. Macroscopic description of teeth of Azara's agouti (Dasyprocta azarae

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    Fabrício S. Oliveira

    2012-01-01

    Full Text Available The teeth of Azara's agouti (Dasyprocta azarae were described macroscopically in order to provide biological data on one of the largest wild rodents of the Americas. Radiography was taken on six heads and the teeth were described. Enamel surrounds the coronal dentin, projects to the roots and is present as parallel inner laminae in buccolingual direction. The dentin is located among the enamel laminae and surrounds the pulp horns. The cementum is located internally to the enamel laminae. On the lingual surface, the cementum and dentin are the outer elements.

  8. Paca (Agouti paca and Agouti (Dasyprocta spp. - Minili-vestock Production in the Amazonas State of Venezuela : 1. Biology

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    Govoni, G.

    2001-01-01

    Full Text Available In response to increasing human population pressure in the Amazonas State of Venezuela greater attention is being given to the "minilivestock" production of the wild rodents paca (Agouti paca, and agouti (Dasyprocta spp as sources of food and income and to reduce the risk of their possible extinction. In preparation for the increased farming of these rodents, this paper reviews published material on their characteristics, distribution, habitat, conservation status, behaviour, reproductive parameters and nutrition. It is concluded that the two rodents paca and agouti, have characteristics that justify greater investment in their domestication and farmed production, although and behavioural issues and reproductive limits need further research.

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

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    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

  10. Placentation in the capybara (Hydrochaerus hydrochaeris), Agouti (Dasyprocta aguti) and paca (Agouti paca).

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    Miglino, M A; Carter, A M; dos Santos Ferraz, R H; Fernandes Machado, M R

    2002-05-01

    Placentae of three hystricimorph rodents--capybara, agouti and paca--were examined by conventional histology, immunohistochemistry for cytokeratin and vimentin, and TUNEL staining. The placentae were divided into lobules of labyrinthine syncytium separated by interlobular and marginal trophoblast. The subplacenta comprised cytotrophoblasts, supported on lamellae of allantoic mesoderm, and syncytiotrophoblast. The central excavation was still apparent in the definitive placenta of capybara. In agouti and paca, the decidua of the junctional zone formed a mesoplacenta comprising a capsule and a pedicle. Towards term the pedicle formed a tenuous attachment between placenta and uterine wall comprising a few maternal vessels surrounded by degraded tissue. In paca placenta, it was shown by TUNEL staining that breakdown of this tissue occurred by apoptosis. The visceral yolk sac was highly villous and, in agouti, the yolk sac villi were extremely long. Lateral to its attachment to the placenta, the fetal surface was covered with non-vascular yolk sac endoderm. A layer of spongiotrophoblast cells was interposed between the endoderm and the marginal trophoblast.

  11. Structural and ultrastructural features of the agouti tongue (Dasyprocta aguti Linnaeus, 1766).

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    Ciena, Adriano Polican; de Sousa Bolina, Cristina; de Almeida, Sonia Regina Yokomizo; Rici, Rose Eli Grassi; de Oliveira, Moacir Franco; da Silva, Marcelo Cavenaghi Pereira; Miglino, Maria Angélica; Watanabe, Ii-sei

    2013-08-01

    The agouti (Dasyprocta aguti Linnaeus, 1766) is a wild rodent belonging to the family Dasyproctidae that is found throughout Brazil and feeds on fruits and seeds. The aim of the present study was to describe the following features of the tongue of agouti: its morphological structures, the three-dimensional characteristics of the lingual papillae surface, the connective tissue cores (CTCs) and the epithelial cell ultrastructure. Four types of papillae were observed on the dorsal surface of the tongue with a triangular shape: filiform, fungiform, foliate and vallate. Filiform papillae were distributed throughout the tongue surface, and removal of the epithelial surface revealed conical CTCs and multifilaments. Fungiform papillae were observed in the rostral and middle regions, whereas foliate papillae developed in pairs on the lateral margin of the caudal region. Removal of the epithelium in these regions revealed CTCs with parallel laminar conformation. Vallate papillae were arranged in a V-shape in the caudal region, and their CTCs ranged in shape from elongate to ovoid. The ultrastructural components of the dorsal epithelium were the basal, spinous, granular and keratinised layers. A broad area with cytoplasmic projections was identified in the interface region between the lamina propria and the basal layer. Flattened cells with intermediate filaments were observed in the transitional region between spinous and granular layers. The keratinised layer was composed of superimposed epithelial cells where desmosomes and cell-surface microridges were observed. These structural features, including the three-dimensional aspects of the lingual papillae, the CTCs and the epithelial ultrastructure, indicate that when compared with other animals, particularly other rodent species, the morphological features of the tongue of agouti are relatively well developed, especially regarding foliate and vallate papillae.

  12. Segmentos anátomo-cirúrgicos arteriais do rim de cutia (Dasyprocta prymnolopha Anatomical-surgical arterial segments of the kidney in agouti (Dasyprocta prymnolopha

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    Maria A.M. Carvalho

    2008-05-01

    Full Text Available Foram estudados 20 pares de rins decutias (Dasyprocta prymnolopha Wagler, 1831, com o objetivo de descrever os segmentos anátomo-cirúrgicos arteriais. As artérias renais foram injetadas com solução de Vinilite corada, e os rins foram submetidos à corrosão ácida para a obtenção dos moldes vasculares. Observou-se que as artérias renais da cutia, sempre únicas, dividiram-se em artéria setorial ventral e artéria setorial dorsal, caracterizando dois setores renais separados por plano avascular. As artérias setoriais penetraram no hilo renal (100% dos casos. Estes vasos deram origem aos ramos segmentares responsáveis pela irrigação de territórios independentes em cada setor, os segmentos arteriais renais. No rim direito foram observados 3 (60%, 4 (35% e 5 segmentos (5% no setor arterial ventral e 3 (30%, 4 (45%, 5 (20% e 6 (5% segmentos no setor dorsal e, à esquerda, 2(10%, 3 (55% e 4 (35% segmentos no setor ventral e 3 (25%, 4 (50% e 5 (25% no dorsal. Com base na distribuição arterial nos rins de cutia, observaram-se setores e segmentos arteriais independentes, sendo possível, desta forma, a realização de setoriectomia e segmentectomia nesta espécie.Twenty pairs of agouti (Dasyprocta prymnolopha Wagler, 1831 kidneys were studied to describe the arterial anatomical-surgical segments. The renal arteries were injected with stained acetate vinyl, followed by procedures of acid corrosion in order to obtain vascular casts. It was found that the renal artery is always single and bifurcated into ventral and dorsal sectorial arteries. The sectorial arteries reached the kidneys (100% of the cases through the hilus. These vessels gave origin to segmental branches responsible for kidney irrigation. At the right kidney, the ventral sectorial arteries gave origin to 3 (60% of the cases, 4 (35% and 5 (5% segmental branches; the dorsal sectorial arteries gave origin to 3 (30%, 4 (45%, 5 (20% and 6 (5% segmental arteries separated by a

  13. 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

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    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

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

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    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.

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

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    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.

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

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    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.

  17. Arterial vascularization of the brain of the agouti (Dasyprocta aguti Linnaeus, 1766

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    Roberto Sávio Bessa da Silva

    2016-04-01

    Full Text Available The agouti, a rodent that is geographically distributed throughout South America, is greatly valued for its meat. This paper describes the arterial vascularization of the base of the agouti’s brain, characterizing behavior, and arterial origin and distribution. Ten animals from the Center for the Multiplication of Wild Animals (CEMAS/UFERSA were used and the study was approved by SISBIO (report number 32413- 1 and the Ethics Committee on Animal Use (CEUA/UFERSA (protocol 02/2010. After euthanasia, the animals were incised in the thoracic cavity by an injection of red-stained Neoprene latex 650 and the skulls were subsequently opened. The brains were extracted from the skulls for ventral surface analysis and then fixed in an aqueous 10% formaldehyde solution. The agouti’s arterial vascularization of the brain has two main components, namely the carotid and vertebrobasilar systems. The agouti’s carotid system accounts for vascularization of almost the entire forebrain, while the vertebrobasilar system accounts for vascularization of almost the entire posterior brain (medulla oblongata, pyramid, trapezoid body, cerebellum, bridge, and part of the third caudal section of the forebrain through the caudal cerebral arteries originating from the terminal branches of the basilar artery. The main arteries on the brain surface include the basilar artery, which is unique, and the arterial pairs, specifically the vertebral arteries, cerebellar caudal arteries, trigeminal artery, rostral cerebellar artery, basilar terminal branch artery, cerebral caudal artery, communicating caudal branch of the cerebral carotid artery, cerebral carotid artery, communicating branch rostral cerebral carotid artery, choroidal rostral artery, medial branch of the communicating branch rostral artery, internal ophthalmic artery, middle cerebral artery, and rostral cerebral artery.

  18. Enfermidades de cutias (Dasyprocta aguti criadas em cativeiro diagnosticadas pelo exame anatomopatológico Diseases of agouti (Dasyprocta aguti raised in captivity diagnosed by pathological examination

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    Jael S. Batista

    2010-06-01

    Full Text Available O exame necroscópico é especialmente útil no diagnóstico de enfermidades em animais silvestres. Em muitas ocasiões, as manifestações clínicas não são características como em animais domésticos, sendo frequente a ocorrência de óbitos em animais assintomáticos. Este trabalho objetivou realizar um estudo retrospectivo sobre as doenças de cutias diagnosticadas pelo Laboratório de Patologia Veterinária da Universidade Federal Rural do Semi-Árido, através do exame anatomopatológico no período de 2006 a 2009. Em 32 cutias submetidas à necropsia, as percentagens das enfermidades diagnosticadas foram: morte perinatal pelo complexo inanição/hipotermia (21,6%, urolitíase obstrutiva (6,24%, distocia (6,24%, obstrução do ceco por areia - sablose (6,24%, intussuscepção (3,20%, fecaloma (3,20% e obstrução do esôfago (3,20%. Dezesseis (16 animais permaneceram sem diagnóstico, dos quais nove (28,48% apresentavam avançado estado autolítico e em sete (21,60% não foram observadas lesões macro e microscópicas compatíveis com nenhuma enfermidade. Este artigo apresenta relatos de doenças ainda não descritas em cutias e seus resultados poderão produzir literatura sobre os aspectos patológicos destas enfermidades nessa espécie.Necroscopic examination is remarkably useful to diagnose wild animal's diseases. In several occasions the clinical signs are not charactheristic as in domestic animals and the occurrence of death in asymptomatic animals is frequent. Thus, the present work aimed to accomplish a retrospective study on agouti diseases diagnosed by pathological examination in the Laboratory of Veterinary Pathology, Federal Rural University of the Semi-arid, through January 2006 to December 2006. In 32 agoutis submitted to the necropsy, the percentage of diagnosed diseases was: perinatal death due hypothermia/ inanition complex (21.6%, obstructive urolithiasis (6.24%, dystocia (6.24%, cecum sablosis (6.24%, intussusceptions

  19. Uso do propofol na indução anestésica de cutias (Dasyprocta sp. Use of propofol in the induction of anesthesia in agouti (Dasyprocta sp.

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    W.P. Leite

    2008-08-01

    Full Text Available Avaliou-se o emprego do propofol, por via intravenosa, como agente indutor anestésico em cutias (Dasyprocta sp, utilizando-se 10 fêmeas adultas, com pesos entre 1,5 a 2,0kg, criadas em cativeiro. Avaliaram-se as freqüências cardíaca e respiratória, a temperatura retal e a pressão arterial sistólica, antes da administração do propofol e logo após a anestesia dos animais. Foram mensurados o período hábil e de recuperação da anestesia. As médias das freqüências cardíaca e respiratória, temperatura retal e a pressão arterial sistólica basais foram de 220bcm, 92mrm, 38,95ºC e 110mmHg, respectivamente. Após a indução, as médias obtidas para essas variáveis foram de 214bcm, 84mrm, 39,05ºC e 80mmHg. As médias dos períodos hábil e de recuperação da anestesia foram de 10min e 45seg e 15min e 40seg, respectivamente. O propofol, quando utilizado em dose única, mostrou-se seguro, não alterando significativamente os parâmetros fisiológicos, podendo ser considerado um fármaco de escolha para a indução anestésica de cutias.The endovenous use of propofol as inductor agent of anesthesia in agouti (Dasyprocta sp. was evaluated using ten adut females, weighing 1.5 to 2.0kg, kept in captivity. Heart and respiratory rates, rectal temperature, and systolic arterial blood pressure were measured before and after anesthesia. Time of anesthesia and time of recovering of the anesthesia were also measured. The averages of the heart and respiratory rates, rectal temperature and the systolic blood pressure were 220bpm, 92mpm, 38.95ºC, and 110Hgmm, respectively. After the induction, the averages obtained for those variables were of 214bpm, 84mpm, 39.05ºC, and 80mmHg, respectively. The averages of the time of anesthesia and time of its recovery were 10min 45sec and 15min 40sec, respectively. Propofol when used in only one dose, was considered safe, since it did not disturbe the physiological parameters. Thus, propofol can be

  20. Determinação da taxa metabólica basal em cutias, Dasyprocta azarae, por calorimetria indireta Determination of the basal metabolic rate in agoutis, Dasyprocta azarae, by indirect calorimetry

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    Harald F.V. Brito

    2010-06-01

    necessidade de novos estudos sobre o metabolismo de Dasyprocta azarae, sugerindo-se a realização de aferição da taxa metabólica basal e aferição simultânea da concentração sérica de testosterona, estradiol e cortisol para os três grupos.The best way to compare different organisms is the basal metabolic rate, a fundamental interrelation existent among all living beings. Direct measures of oxygen and carbon dioxide concentrations by evaluation of inspired and expired air can be used to measure metabolic rate. So, this research was done in order to measure basal and specific metabolic rates in agoutis (Dasyprocta azarae, and reexamine the scaling of basal metabolism in this species. There were used 34 adult healthy agoutis (9 non-castrated males, 9 castrated males, and 16 females, that belong to the wild animal scientific breeding facility of the Natural History Museum of the Curitiba city, State of Paraná, Brazil. After a six-hour fasting the animals were placed in special boxes under controlled temperature (22.0±1.0ºC, and submitted to measuring of the basal metabolic rate, by indirect calorimetry. It was used the Deltatrac®II metabolic monitor, usually indicated to measure carbon dioxide production (VCO2 and oxygen consumption (VO2 in human beings, by measuring variations in the concentration of VCO2 and of VO2, with a precision of 0.01%. The specific metabolic rate was calculated after determination of the basal metabolic rate and the obtained data were analyzed by inductive statistics. The hypotheses tests for comparison among samples indicated that the specific metabolic rate is higher in non-castrated males than in females and castrated males (significance of 5%, and that the specific metabolic rate of females and castrated males are equivalent (significance of 1%. In addition, analysis of the correlation of experimental points indicates that another variable beyond body size affects the metabolic rate of non-castrated males (significance of 1%, and

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

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    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

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

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    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.

  3. Níveis iônicos e enzimáticos de cutias (Dasyprocta sp. hígidas, criadas em cativeiro, influência do sexo e da idade Ion and enzymatic levels of healthy agouti (Dasyprocta sp. raised in captivit. Influence of gender and age

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    E.E.A. Ribeiro

    2008-06-01

    Full Text Available Determinou-se o perfil do ionograma e enzimas hepáticas de cutias (Dasyprocta sp. saudáveis, criadas em cativeiro, como também se avaliou a influência de sexo, idade e interação sexo-idade. Foi adotado um delineamento inteiramente ao acaso, em arranjo fatorial 2 x 4 (dois sexos e quatro faixas etárias, com três repetições, totalizando 24 cutias. Foram determinados os valores para o cálcio (Ca, fósforo (P, cloretos (Cl, aspartato aminotransferase (AST, alanina aminotransferase (ALT, fosfatase alcalina (FA e gama-glutamiltransferase (GGT. Os valores médios obtidos foram: Ca= 7,62+2,59mg/dl; P= 3,91+1,41mg/dl; Cl= 58,63+16,45mg/dl; AST= 119,54+79,35UI/ml; ALT= 28,08+15,53UI/ml; FA= 26,95+14,01UI/ml e GGT= 25,34+19,44UI/ml. O valor de P foi maior nas fêmeas e da FA nos machos. Os níveis de FA diminuíram com o aumento da idade.This research studied the profile of the ionogram and hepatic enzymes of healthy agoutis (Dasyprocta sp. raised in captivity as well as evaluated the influence of gender, age and interaction gender-age. It was used a completely randomized design, in a factorial arrangement of 2 x 4 (two genders and four age groups, with three repetitions, totaling 24 agoutis. The values were determined for calcium (Ca, phosphorus (P, chlorides (Cl, aspartate aminotransaminase (AST, alanine aminotransaminase (ALT, alkaline phosphatase (ALP, and gamma-glutamyltransferase (GGT. The mean values were: Ca= 7.62±2.59mg/dl; P= 3.91±1.41mg/dl; Cl= 58.63±16,45mg/dl; AST= 119.54±79.35UI/ml; ALT= 28.08±15.53UI/ml; ALP= 26.95±14.01UI/ml, and GGT= 25.34±19.44UI/ml. The value of P was larger in females and ALP in males. As the age increased, levels of ALP decreased.

  4. Desempenho de cutias (Dasyprocta prymnolopha criadas em cativeiro do nascimento até o desmame em Teresina, Piauí Performance of agouti (Dasyprocta prymnolopha bred in captivity according to sex and parturition in Teresina, Piauí

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    João Batista Lopes

    2004-12-01

    Full Text Available Objetivou-se avaliar a influência do sexo e do tipo de parto (simples ou duplo sobre peso, comprimento corporal, perímetro torácico ao nascer e ao desmame de cutias, bem como o ganho de peso total e o ganho médio diário, em busca de subsídios que contribuam para a preservação e a exploração racional desses animais. Foram avaliados 41 animais (26 machos e 15 fêmeas, em delineamento experimental inteiramente casualizado em esquema fatorial 2x2, associando-se os tratamentos: sexo (macho, fêmea e tipo de parto (duplo e simples. O peso médio, o perímetro torácico médio, o comprimento corporal dos filhotes ao nascer para, machos e fêmeas, foram de 147,62 g e 146,25 g; 12,26 cm e 12,17 cm; 19,91 cm e 19,39 cm, respectivamente. Para as mesmas variáveis, os valores ao desmame para machos e fêmeas foram 481,92 g e 509,33 g; 17,12 cm e 16,85 cm; 30,07 cm e 30,42 cm, respectivamente. Não houve diferença significativa entre os parâmetros avaliados, quando comparados ao sexo e ao tipo de parto (simples ou duplo. Concluiu-se que o peso de filhotes de cutia ao nascer e ao desmame não tem relação com o sexo e o tipo de parto; o peso médio, o comprimento corporal e o perímetro torácico de filhotes de cutia ao nascer e ao desmame, respectivamente, são, para ambos os sexos, em torno de 145 g e 500 g, 20 e 30 cm e 12 e 17 cm; o ganho de peso médio diário do nascer ao desmame é de 7,76 g.This experiment was carried out to evaluate the effect of sex and parturition type (simple or double on live weight, body length, thoracic diameter at birth and at weaning of agouti, as well as total weight gain and daily mean weight gain, to obtain subsidies that contribute to preservation and rational exploration of these animals. Fourty-one animals (26 males and 15 females were allotted to a completely randomized a design. Animal weight, thoracic diameter and body length of agouti at birth, for males and females, were respectively: 147.62 g and 146

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

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    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.

  6. Karyotypic analysis in species of the genus Dasyprocta (Rodentia: Dasyproctidae found in Brazilian Amazon

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    ROSEMAR S. L. RAMOS

    2003-03-01

    Full Text Available A total of 30 animals of the genus Dasyprocta were cytogenetically studied. They belong to the following species: D. prymnolopha (N=20, D. leporina (N=6, D. fuliginosa (N=1 and Dasyprocta sp. (N=3 (Dasyproctidae, Hystricognathi. Cell suspensions were obtained by peripheral blood culture, besides bone marrow and spleen cells, from D. prymnolopha and D. leporina. The diploid number was 64/65 for all samples. The karyotypes showed similarity, and chromosomal polymorphism was not detected by Giemsa conventional staining and G banding. The constitutive heterochromatin distribution at the pericentromeric region of all the chromosomes was similar in all species. D. prymnolopha, D. leporina and Dasyprocta sp. presented variation in the heterochromatical block size at one of the homologues of the A18 pair. D. fuliginosa presented the heterochromatin uniformly distributed in all chromosomes. There was not variation in the NORs pattern in the species studied.Foram estudados citogeneticamente um total de 30 animais das espécies D. prymnolopha (N=20, D. leporina (N=6, D. fuliginosa (N=1 e Dasyprocta sp. (N=3 (Dasyproctidae, Histricognathi. As preparações cromossômicas foram obtidas do cultivo de sangue periférico, além de medula óssea e baço em D. prymnolopha e D. leporina. O número diplóide foi de 64/65 em todos os exemplares. O cariótipo mostrou similaridade, não sendo detectado, através de coloração convencional de giemsa e de banda G, polimorfismo cromossômico em qualquer uma das espécies estudadas. A distribuição da heterocromatina constitutiva na região pericentromérica de todos os cromossomos foi similar nas quatro espécies. D. prymnolopha, D. leporina e Dasyprocta sp. apresentaram variação no tamanho do bloco heterocromático em um dos homólogos do par A18. D. fuliginosa apresentou a heterocromatina uniformemente distribuída em todos os cromossomos. Não houve variação no padrão das RONs entre as esp��cies estudadas.

  7. 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

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    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

  8. Seed predation and defleshing in the agouti-dispersed palm Astrocaryum standleyanum

    NARCIS (Netherlands)

    Jansen, P.A.; Elschot, K.; Verkerk, P.J.; Wright, S.J.

    2010-01-01

    The agouti (Dasyprocta punctata) meticulously defleshes Astrocaryum standleyanum palm seeds before scatter hoarding. On Barro Colorado Island, Panama, we experimentally tested three hypotheses on how this behaviour could reduce seed predation to the mutual benefit of the tree and the rodent. The fir

  9. Morfologia das glândulas salivares maiores em cutias (Dasyprocta leporina Linnaeus, 1766

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    Carlos M. Oliveira Júnior

    2016-03-01

    Full Text Available Resumo: Estudos acerca da morfologia de animais silvestres servem de subsídio para trabalhos de manejo e preservação de diferentes espécies, pois fornecem informações para a tomada de medidas que auxiliem na manutenção destes em cativeiro, na preservação em habitat natural ou mesmo para ações voltadas a reintrodução ao habitat de origem. Estudos referentes à morfologia de cutias abordam os diversos sistemas, mas nenhum faz referência à arquitetura ou estrutura de suas glândulas salivares. Assim este trabalho objetivou descrever macro e microscopicamente as glândulas salivares maiores de cutias. Foram utilizados dez animais adultos para o desenvolvimento de metodologias relativas à macroscopia propriamente dita das glândulas, microscopia de luz, microscopia eletrônica de transmissão e microscopia eletrônica de varredura. Foram identificadas quatro glândulas salivares maiores nos animais estudados, denominadas parótida, mandibular, zigomática e sublingual. As glândulas apresentaram-se como sendo do tipo tubuloacinares e contendo em seu parênquima ductos dos mais variados tamanhos. Com exceção da glândula parótida, que era estritamente serosa, as demais eram mistas. Da mesma forma, apenas a glândula mandibular foi identificada a presença de ducto do tipo granuloso. Apresentando as cutias os quatro pares de glândulas salivares maiores, estes animais podem servir de modelo para os estudos acerca das mudanças anatômicas sofridas pelos roedores para se adaptar aos diversos habitat do planeta.

  10. Seed predation and defleshing in the agouti-dispersed palm Astrocaryum standleyanum

    OpenAIRE

    Jansen, P.A.; Elschot, K.; Verkerk, P. J.; Wright, S. J.

    2010-01-01

    The agouti (Dasyprocta punctata) meticulously defleshes Astrocaryum standleyanum palm seeds before scatter hoarding. On Barro Colorado Island, Panama, we experimentally tested three hypotheses on how this behaviour could reduce seed predation to the mutual benefit of the tree and the rodent. The first and established hypothesis – that defleshing reduces seed predation by bruchid beetles by intercepting larvae – was rejected. Experiments in which manually defleshed seeds or entire fruits were ...

  11. Morfologia da laringe de cutia (Dasyprocta sp.

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    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.

  12. Modulation of social behavior by the agouti pigmentation gene

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    Valeria eCarola

    2014-08-01

    Full Text Available Agouti is a secreted neuropeptide that acts as an endogenous antagonist of melanocortin receptors. Mice and rats lacking agouti (called non-agouti have dark fur due to a disinhibition of melanocortin signaling and pigment deposition in the hair follicle. Non-agouti animals have also been reported to exhibit altered behavior, despite no evidence for the expression of agouti outside the skin. Here we confirm that non-agouti mice show altered social behavior and uncover expression of agouti in the preputial gland, a sebaceous organ in the urinary tract that secretes molecules involved in social behavior. Non-agouti mice had enlarged preputial glands and altered levels of putative preputial pheromones and surgical removal of the gland reversed the behavioral phenotype. These findings demonstrate the existence of an autologous, out-of-skin pathway for the modulation of social behavior.

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

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    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

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

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    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

  15. Bioactive motifs of agouti signal protein.

    Science.gov (United States)

    Virador, V M; Santis, C; Furumura, M; Kalbacher, H; Hearing, V J

    2000-08-25

    The switch between the synthesis of eu- and pheomelanins is modulated by the interaction of two paracrine signaling molecules, alpha-melanocyte stimulating hormone (MSH) and agouti signal protein (ASP), which interact with melanocytes via the MSH receptor (MC1R). Comparison of the primary sequence of ASP with the known MSH pharmacophore provides no suggestion about the putative bioactive domain(s) of ASP. To identify such bioactive motif(s), we synthesized 15-mer peptides that spanned the primary sequence of ASP and determined their effects on the melanogenic activities of murine melanocytes. Northern and Western blotting were used, together with chemical analysis of melanins and enzymatic assays, to identify three distinct bioactive regions of ASP that down-regulate eumelanogenesis. The decrease in eumelanin production was mediated by down-regulation of mRNA levels for tyrosinase and other melanogenic enzymes, as occurs in vivo, and these effects were comparable to those elicited by intact recombinant ASP. Shorter peptides in those motifs were synthesized and their effects on melanogenesis were further investigated. The amino acid arginine, which is present in the MSH peptide pharmacophore (HFRW), is also in the most active domain of ASP (KVARP). Our data suggest that lysines and an arginine (in motifs such as KxxxxKxxR or KxxRxxxxK) are important for the bioactivity of ASP. Identification of the specific ASP epitope that interacts with the MC1R has potential pharmacological applications in treating dysfunctions of skin pigmentation.

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

    OpenAIRE

    Weber Leal de Moura; Adriana Maria Viana Nunes Pinheiro; Débora Cavalcante Braz; Maria Acelina de Carvalho

    2006-01-01

    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...

  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

    Science.gov (United States)

    Woychik, Richard P.

    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. Induction of brain region-specific forms of obesity by Agouti

    NARCIS (Netherlands)

    Kas, M.J.H.; Tiesjema, B; van Dijk, G; Garner, KM; Barsh, GS; Ter Brake, O; Verhaagen, J; Adan, RAH

    2004-01-01

    Disruption of melanocortin ( MC) signaling, such as by ectopic Agouti overexpression, leads to an obesity syndrome with hyperphagia, obesity, and accelerated body weight gain during high-fat diet. To investigate where in the brain disruption of MC signaling results in obesity, long-term Agouti expre

  2. Induction of brain-region-specific forms of obesity by agouti

    NARCIS (Netherlands)

    Kas, Martien J H; Tiesjema, Birgitte; van Dijk, Gertjan; Garner, Keith M; Barsh, Gregory S; ter Brake, Olivier; Verhaagen, Joost; Adan, Roger A H

    2004-01-01

    Disruption of melanocortin (MC) signaling, such as by ectopic Agouti overexpression, leads to an obesity syndrome with hyperphagia, obesity, and accelerated body weight gain during high-fat diet. To investigate where in the brain disruption of MC signaling results in obesity, long-term Agouti expres

  3. 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

  4. 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.

  5. Molecular structure and chromosomal mapping of the human homolog of the agouti gene

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, H.Y.; Woychik, R.P. [Oak Ridge National Lab., TN (United States); Bultman, S.J. [Oak Ridge National Lab., TN (United States)]|[Univ. of Tennessee, Oak Ridge, TN (United States); Loeffler, C.; Hansmann, I. [Universitaet Goettingen (Germany); Chen, W.J.; Furdon, P.J.; Wilkison, W. [Glaxo Research Institute, Research Triangle Park, NC (United States); Powell, J.G.; Usala, A.L. [Eastern Carolina Univ., Greenville, NC (United States)

    1994-10-11

    The agouti (a) locus in mouse chromosome 2 normally regulates coat color pigmentation. The mouse agouti gene was recently cloned and shown to encode a distinctive 131-amino acid protein with a consensus signal peptide. Here the authors describe the cloning of the human homolog of the mouse agouti gene using an interspecies DNA-hybridization approach. Sequence analysis revealed that the coding region of the human agouti gene is 85% identical to the mouse gene and has the potential to encode a protein of 132 amino acids with a consensus signal peptide. Chromosomal assignment using somatic-cell-hybrid mapping panels and fluorescence in situ hybridization demonstrated that the human agouti gene maps to chromosome band 20q11.2. This result revealed that the human agouti gene is closely linked to several traits, including a locus called MODY (for maturity onset diabetes of the young) and another region that is associated with the development of myeloid leukemia. Initial expression studies with RNA from several adult human tissues showed that the human agouti gene is expressed in adipose tissue and testis.

  6. Experimental heteroxenous cycle of Lagochilascaris minor Leiper, 1909 (Nematoda: Ascarididae in white mice and in cats

    Directory of Open Access Journals (Sweden)

    Gregorio S. Volcan

    1992-12-01

    Full Text Available Reports of natural infections of sylvatic carnivores by adult worms of species similar to Lagochilascaris minor in the Neotropical region led to attempts to estabilish experimental cycles in laboratory mice and in cats. Also, larval development was seen in the skeletal muscle of an agouti (Dasyprocta leporina infected per os with incubated eggs of the parasite obtained from a human case. In cats, adult worms develop and fertile eggs are expelled in the feces: in mice, larval stages of the parasite develop, and are encapsulate in the skeletal muscle, and in the adipose and subcutaneous connective tissue. From our observations, we conclude that the larva infective for the mouse is the early 3rd stage, while for the final host the infective form is the later 3rd stage. A single moult was seen in the mouse, giving rise to a small population of 4th stage larvae, long after the initial infection.

  7. [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.

  8. Identification of distant Agouti-like sequences and re-evaluation of the evolutionary history of the Agouti-related peptide (AgRP.

    Directory of Open Access Journals (Sweden)

    Åke Västermark

    Full Text Available The Agouti-like peptides including AgRP, ASIP and the teleost-specific A2 (ASIP2 and AgRP2 peptides have potent and diverse functional roles in feeding, pigmentation and background adaptation mechanisms. There are contradictory theories about the evolution of the Agouti-like peptide family as well the nomenclature. Here we performed comprehensive mining and annotation of vertebrate Agouti-like sequences. We identified A2 sequences from salmon, trout, seabass, cod, cichlid, tilapia, gilt-headed sea bream, Antarctic toothfish, rainbow smelt, common carp, channel catfish and interestingly also in lobe-finned fish. Moreover, we surprisingly found eight novel homologues from the kingdom of arthropods and three from fungi, some sharing the characteristic C-x(6-C-C motif which are present in the Agouti-like sequences, as well as approximate sequence length (130 amino acids, positioning of the motif sequence and sharing of exon-intron structures that are similar to the other Agouti-like peptides providing further support for the common origin of these sequences. Phylogenetic analysis shows that the AgRP sequences cluster basally in the tree, suggesting that these sequences split from a cluster containing both the ASIP and the A2 sequences. We also used a novel approach to determine the statistical evidence for synteny, a sinusoidal Hough transform pattern recognition technique. Our analysis shows that the teleost AgRP2 resides in a chromosomal region that has synteny with Hsa 8, but we found no convincing synteny between the regions that A2, AgRP and ASIP reside in, which would support that the Agouti-like peptides were formed by whole genome tetraplodization events. Here we suggest that the Agouti-like peptide genes were formed through classical subsequent gene duplications where the AgRP is the most distantly related to the three other members of that group, first splitting from a common ancestor to ASIP and A2, and then later the A2 split from ASIP

  9. 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.

  10. Pheomelanin production in the epidermis from newborn agouti mice is induced by the expression of the agouti gene in the dermis.

    Science.gov (United States)

    Hirobe, Tomohisa; Takeuchi, Sakae; Hotta, Eri; Wakamatsu, Kazumasa; Ito, Shosuke

    2004-10-01

    The present study was designed to clarify the role of the agouti gene in the regulation of the proliferation and differentiation of mouse epidermal melanocytes using serum-free primary culture of epidermal melanocytes from 0.5-d-old black (a/a; C57BL/10JHir) mice and congenic, agouti (A/A; C57BL/10JHir-A/A) mice. There was no significant difference in the proliferation or differentiation of melanocytes between a/a and A/A mice. However, the content of pheomelanin in culture media from A/A melanocytes was increased by L-tyrosine compared with a/a melanocytes. In addition, the content of the pheomelanin precursor, 5-S-cysteinyldopa, in culture media from A/A melanocytes was dramatically increased by L-tyrosine. Moreover, pheomelanin content in the epidermis from 3.5- and 5.5-d-old A/A mice was much higher than in a/a mice. Analysis of the A gene using reverse transcription-polymerase chain reaction revealed that cultured keratinocytes and melanocytes do not express the A gene. Moreover, the A gene was expressed in the A/A dermis of 0.5-, 3.5- and 5.5-d-old mice, but not in the a/a dermis nor in the A/A or a/a epidermis. These results suggest that A/A epidermal melanoblasts are influenced by the A gene from the dermis of neonatal mice, and are capable of synthesizing pheomelanin in the culture. Pheomelanin production in the epidermis from 3.5- and 5.5-d-old A/A mice may be induced by the expression of the agouti gene in the dermis.

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

    OpenAIRE

    Lizcano L.; Estrada G.; Orozco O.; Núñez P.

    2006-01-01

    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 espectrofotométric...

  12. 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.

  13. 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.

  14. 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.

  15. Molecular basis of the pleiotropic phenotype of mice carrying the hypervariable yellow (A{sup hvy}) mutation at the agouti locus

    Energy Technology Data Exchange (ETDEWEB)

    Argeson, A.C.; Nelson, K.K.; Siracusa, L.D. [Jefferson Cancer Center, Philadelphia, PA (United States)

    1996-02-01

    The murine agouti locus regulates a switch in pigment synthesis between eumelanin (black/brown pigment) and phaeomelanin (yellow/red pigment) by hair bulb melanocytes. We recently described a spontaneous mutation, hypervariable yellow (A{sup hvy}) and demonstrated that A{sup hvy} is responsible for the largest range of phenotypes yet identified at the agouti locus, producing mice that are obese with yellow coats to mice that are of normal weight with black coats. Here, we show that agouti expression is altered both temporally and spatially in A{sup hvy} mutants. Agouti expression levels are positively correlated with the degree of yellow pigmentation in individual A{sup hvy} mice, consistent with results from other dominant yellow agouti mutations. Sequencing of 5{prime} RACE and genomic PCR products revealed that A{sup hvy} resulted from the integration of an intracisternal A particle (IAP) in an antisense orientation within the 5{prime} untranslated agouti exon 1C. This retrovirus-like element is responsible for deregulating agouti expression in A{sup hvy} mice; agouti expression is correlated with the methylation state of CpG residues in the IAP long terminal repeat as well as in host genomic DNA. In addition, the data suggest that the variable phenotype of A{sup hvy} offspring is influenced in part by the phenotype of their A{sup hvy} female parent. 42 refs., 7 figs., 1 tab.

  16. Combined blockade of both mu- and kappa-opioid receptors prevents the acute orexigenic action of agouti-related protein

    NARCIS (Netherlands)

    Brugman, S; Clegg, DJ; Woods, SC; Seeley, RJ

    2002-01-01

    Agouti-related protein (AgRP) is an endogenous antagonist at the melanocortin 3 and 4 receptor in the hypothalamus. Central administration of AgRP produces a robust increase in food intake, and this effect can be blocked by administration of nonspecific opioid receptor antagonist. Such results impli

  17. Characterization, tissue distribution and regulation by fasting of the agouti family of peptides in the sea bass (Dicentrarchus labrax).

    Science.gov (United States)

    Agulleiro, Maria Josep; Cortés, Raúl; Leal, Esther; Ríos, Diana; Sánchez, Elisa; Cerdá-Reverter, José Miguel

    2014-09-01

    The melanocortin system is one of the most complex hormonal systems in vertebrates. Atypically, the signaling of melanocortin receptors is regulated by the binding of endogenous antagonists, named agouti-signaling protein (ASIP) and agouti-related protein (AGRP). Teleost specific genome duplication (TSGD) rendered new gene copies in teleost fish and up to four different genes of the agouti family of peptides have been characterized. In this paper, molecular cloning was used to characterize mRNA of the agouti family of peptides in sea bass. Four different genes were identified: AGRP1, ASIP1, AGRP2 and ASIP2. The AGRP1 gene is mainly expressed in the brain whereas ASIP1 is mainly expressed in the ventral skin. Both ASIP2 and AGRP2 are expressed in the brain and the pineal gland but also in some peripheral tissues. Immunocytochemical studies demonstrated that AGRP1 is exclusively expressed within the lateral tuberal nucleus, the homologue of the mammalian arcuate nucleus in fish. Long-term fasting (8-29 days) increased the hypothalamic expression of AGRP1 but depressed AGRP2 expression (15-29 days). In contrast, the hypothalamic expression of ASIP2 was upregulated during short-term fasting suggesting that this peptide could be involved in the short term regulation of food intake in the sea bass.

  18. Agouti and Agouti-related Proteins%Agouti和Agouti相关蛋白的一些生物学内涵

    Institute of Scientific and Technical Information of China (English)

    杨云青; 高丹玫; 郭宗圣

    2008-01-01

    Agouti 有多方面的意义.首先,它是分属几种不同物种的哺乳动物的俗称.其次,它是一些啮齿类动物的属名.第三,它代表了一种啮齿类动物特有的毛色.第四,它是一个与黑素皮质素受体信号转导途径的调控有关,存在于从人(Homo sapiens)到啮齿类动物,乃至斑马鱼(Danio rerio)的一个特定基因的名称,又是该基因产生的一种特定信号蛋白的名称.Agouti和Agouti相关蛋白是肿瘤、肥胖与糖尿病等人类疾病的研究热点之一.Agouti黄色肥胖小鼠最近成了表观遗传学研究的一个重要模型动物.本文阐述并区分了与agouti有关的一些重要概念与科学术语,并综述了相关领域的研究进展.

  19. Induction of neuropeptide Y gene expression in the dorsal medial hypothalamic nucleus in two models of the agouti obesity syndrome.

    Science.gov (United States)

    Kesterson, R A; Huszar, D; Lynch, C A; Simerly, R B; Cone, R D

    1997-05-01

    Dominant mutations at the agouti locus induce several phenotypic changes in the mouse including yellow pigmentation (phaeomelanization) of the coat and adult-onset obesity. Nonpigmentary phenotypic changes associated with the agouti locus are due to ectopic expression of the agouti-signaling protein (ASP), and the pheomelanizing effects on coat color are due to ASP antagonism of alpha-MSH binding to the melanocyte MC1 receptor. Recently it has been demonstrated that pharmacological antagonism of hypothalamic melanocortin receptors or genetic deletion of the melanocortin 4 receptor (MC4-R) recapitulates aspects of the agouti obesity syndrome, thus establishing that chronic disruption of central melanocortinergic signaling is the cause of agouti-induced obesity. To learn more about potential downstream effectors involved in these melanocortinergic obesity syndromes, we have examined expression of the orexigenic peptides galanin and neuropeptide Y (NPY), as well as the anorexigenic POMC in lethal yellow (A(y)), MC4-R knockout (MC4-RKO), and leptin-deficient (ob/ob) mice. No significant changes in galanin or POMC gene expression were seen in any of the obese models. In situ hybridizations using an antisense NPY probe demonstrated that in obese A(y) mice, arcuate nucleus NPY mRNA levels were equivalent to that of their C57BL/6J littermates. However, NPY was expressed at high levels in a new site, the dorsal medial hypothalamic nucleus (DMH). Expression of NPY in the DMH was also seen in obese MC4-RKO homozygous (-/-) mice, but not in lean heterozygous (+/-) or wild type (+/+) control mice. This identifies the DMH as a brain region that is functionally altered by the disruption of melanocortinergic signaling and suggests that this nucleus, possibly via elevated NPY expression, may have an etiological role in the melanocortinergic obesity syndrome.

  20. 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

  1. Erupção dental em pacas (Agouti paca criadas em cativeiro Dental eruption in pacas (Agouti paca bred in captivity

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    F.S. Oliveira

    2007-04-01

    Full Text Available Fez-se o acompanhamento radiográfico mensal da erupção dental de cinco fêmeas e sete machos da espécie Agouti paca durante 30 meses. Os animais foram radiografados mês-a-mês. As pacas nasceram com três dentes em cada hemiarcada dental, um incisivo de crescimento contínuo por toda a vida, um pré-molar decíduo (o único que é decíduo e um molar. No quarto mês houve a erupção do segundo molar. O nivelamento da superfície de oclusão dos dentes inferiores ocorreu no sexto mês e o dos superiores ao redor do nono mês. No 14° mês, houve o início da erupção do terceiro molar e, no 16° mês, a evidenciação radiográfica do pré-molar permanente, ainda com preservação de correspondente decíduo. No 21° mês, ocorreu o nivelamento da superfície de oclusão dos quatro dentes superiores e inferiores. Entre o 22° e o 24° mês, iniciou-se a queda dos pré-molares decíduos inferiores e, entre o 23º e o 24° mês, a dos superiores. Entre o 24º e o 25º mês, a superfície de oclusão dos dentes inferiores estava nivelada, e a dos dentes superiores aconteceu no 27º mês.Five females and seven males of Agouti paca were used to study dental eruption. In a monthly radiographic survey of the dental eruption, during 30 consecutive months, animals were radiographed. Pacas were born with three teeth in each dental hemiarcade, one incisor of continuous growth, one premolar (the only one deciduous and one molar. The second molar erupted in the fourth month. The occlusal surfaces of lower teeth were at the same level in the sixth month and the upper teeth around ninth month. The beginning of the third molar eruption occurred in the 14th month. Perception of the first permanent premolar was around the 16th month, and its correspondent deciduous was still retained. The occlusal surfaces of upper and lower teeth were at the same level in the 21st month. The eruption of the first lower deciduous premolar occurred between the 22nd and 24th

  2. 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.

  3. 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.

  4. A polymorphism in the human agouti-related protein is associated with late-onset obesity.

    Science.gov (United States)

    Argyropoulos, George; Rankinen, Tuomo; Neufeld, Doni R; Rice, Treva; Province, Michael A; Leon, Arthur S; Skinner, James S; Wilmore, Jack H; Rao, D C; Bouchard, Claude

    2002-09-01

    The mouse agouti-related protein (AGRP) is a powerful appetite effector that results in hyperphagia and the development of obesity when administered intracerebroventricularly or when overexpressed in transgenic mice. Animal studies have also shown that exogenous administration of AGRP predisposes toward hedonic intake of high fat and high sucrose diets. The human ortholog (hAGRP) maps on chromosome 16q22 and has similar physiological properties, as tested in animal models. A polymorphism was identified in the third exon of hAGRP, c.199G-->A, that resulted in a nonconservative amino acid substitution, Ala(67)Thr. Computational analysis of the protein showed significant differences in the coils of the two polymorphic isoforms of the protein. Human studies showed no genotype effects in individuals with a mean age of 25 yr. However, the G/G genotype was significantly associated with fatness and abdominal adiposity in the parental population with a mean age of 53 yr. The c.199G-->A polymorphism in hAGRP could, therefore, play a role in the development of human obesity in an age-dependent fashion.

  5. Transient ectopic overexpression of agouti-signalling protein 1 (asip1 induces pigment anomalies in flatfish.

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    Raúl Guillot

    Full Text Available While flatfish in the wild exhibit a pronounced countershading of the dorso-ventral pigment pattern, malpigmentation is commonly observed in reared animals. In fish, the dorso-ventral pigment polarity is achieved because a melanization inhibition factor (MIF inhibits melanoblast differentiation and encourages iridophore proliferation in the ventrum. A previous work of our group suggested that asip1 is the uncharacterized MIF concerned. In order to further support this hypothesis, we have characterized asip1 mRNAs in both turbot and sole and used deduced peptide alignments to analyze the evolutionary history of the agouti-family of peptides. The putative asip precursors have the characteristics of a secreted protein, displaying a putative hydrophobic signal. Processing of the potential signal peptide produces mature proteins that include an N-terminal region, a basic central domain with a high proportion of lysine residues as well as a proline-rich region that immediately precedes the C-terminal poly-cysteine domain. The expression of asip1 mRNA in the ventral area was significantly higher than in the dorsal region. Similarly, the expression of asip1 within the unpigmented patches in the dorsal skin of pseudoalbino fish was higher than in the pigmented dorsal regions but similar to those levels observed in the ventral skin. In addition, the injection/electroporation of asip1 capped mRNA in both species induced long term dorsal skin paling, suggesting the inhibition of the melanogenic pathways. The data suggest that fish asip1 is involved in the dorsal-ventral pigment patterning in adult fish, where it induces the regulatory asymmetry involved in precursor differentiation into mature chromatophore. Adult dorsal pseudoalbinism seems to be the consequence of the expression of normal developmental pathways in an inaccurate position that results in unbalanced asip1 production levels. This, in turn, generates a ventral-like differentiation environment

  6. Alterações patológicas do sistema genital de cutias (Dasyprocta aguti Linnaeus, 1758 fêmeas criadas em cativeiro

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    Jael S. Batista

    Full Text Available Resumo: Este artigo apresenta relatos de sete distintas patologias de origem reprodutiva ainda não descritas em cutias (Dasyprocta aguti Linnaeus, 1758 fêmeas, que afetaram a fertilidade ou resultaram na morte do animal. Descreveu-se a natureza, a localização e a frequência das alterações patológicas macroscópicas e histológicas dos órgãos que compõem o sistema reprodutivo de cutias fêmeas, criadas sob condições de cativeiro no semiárido do Brasil. Foram avaliados através do exame anatomopatológico o aparelho reprodutivo de trinta e nove cutias mortas naturalmente e encaminhadas ao Laboratório de Patologia Veterinária, no período de fevereiro de 2010 a maio de 2015. Destas, constatou-se alterações patológicas no sistema reprodutivo de 10 (25,6 %. No total, 13 alterações foram observadas, sendo que, em alguns animais haviam a coexistência de mais de uma alteração. Assim, as alterações patológicas encontradas foram: endometrite (n=4; 30,8%, piometra (n=3; 23%, retenção de placenta (n=2; 15,4%, maceração fetal (n=1; 7,7%, mumificação fetal (n=1; 7,7%, parto distócico (n=1; 7,7% e ovários afuncionais (n=1; 7,7%.

  7. 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

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    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.

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

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    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. 藏羊刺鼠信号蛋白基因(Agouti)的多态性及不同颜色被毛皮肤组织中Agouti与小眼畸形相关转录因子基因(MITF)表达的定量分析%The Polymorphism of Agouti Signaling Protein Gene (Agouti) and the Expression of A gouti and Microphthalmia-associated Transcription Factor Gene MITF in Different Coat Color Skin Tissues of Tibetan Sheep (Ovis aries)

    Institute of Scientific and Technical Information of China (English)

    韩吉龙; 岳耀敬; 裴杰; 郭婷婷; 刘建斌; 郭健; 孙晓萍; 冯瑞林; 杨博辉

    2013-01-01

    为了研究决定藏羊不同颜色被毛形成的分子机制,首先对绵羊(Ovis aries)毛色的主要候选基因刺鼠信号蛋白基因(agouti signaling protein (ASIP) gene,Agouti)的多态性进行了检测,然后对该基因外显子2和外显子4的功能突变和该基因的拷贝数变异分别与毛色进行了相关性分析;同时开展实时荧光定量PCR检测皮肤组织中Agouti和小眼畸形相关转录因子基因(microphthalmia-associated transcriptionfactor,MITF) mRNA的相对表达量,分析同一基因在黑色眼圈、棕黑色颈部和白色体侧被毛皮肤组织的相对表达量差异,对两基因在同一个体同一颜色被毛皮肤组织表达量进行相关性分析.结果表明,A gouti基因的外显子的单核苷酸多态性(SNP)多态性与毛色不相关,该基因的拷贝数变异(CNV)与毛色也不相关.同一个体Agouti基因mRNA表达水平为棕黑色皮肤组织显著高于黑色和白色(P<0.05),MITF基因mRNA表达量为黑色皮肤组织显著高于棕黑色和白色(P<0.05).通过相关性分析得知,两基因在同一个体同一毛色皮肤组织内mRNA相对表达量无显著相关性.研究结果提示,Agouti基因的多态性与藏羊的毛色不具有相关关系,MITF基因mRNA表达量可能与藏羊眼圈周围黑色被毛相关,Agouti基因mRNA表达量、MITF基因mRNA表达量可能对颈部棕黑色被毛有一定作用,体侧部的白色毛与Agouti和MITF基因mRNA表达量无明显相关.%In order to study the molecular mechanism that determines the formation of the coat color in different coat color of Tibetan sheep(Ovis aries) skin tissues, agouti signaling protein gene (Agouti) as the main candidate gene about coat color, Agouti gene's polymorphisms were detected firstly, then associated coat color with the exon 2, exon 4 function mutations and the gene copy number variation (CNV) of Agouti, as well as the Real-time fluorescent quantitative PCR was adopted to detect mRNA's relative

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

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    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.

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

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    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.

  13. Disulfide assignment of the C-terminal cysteine knot of agouti-related protein (AGRP) by direct sequencing analysis.

    Science.gov (United States)

    Young, Y; Zeni, L; Rosenfeld, R D; Stark, K L; Rohde, M F; Haniu, M

    1999-12-01

    We have assigned the disulfide structure of Md-65 agouti-related protein (Md65-AGRP) using differential reduction and alkylation followed by direct sequencing analysis. The mature human AGRP is a single polypeptide chain of 112 amino acid residues, consisting of an N-terminal acidic region and a unique C-terminal cysteine-rich domain. The C-terminal domain, a 48 amino acid peptide named Md65-AGRP, was expressed in Escherichia coil cells and refolded under different conditions from the mature recombinant protein. The disulfide bonds in the cystine knot structure of Md65-AGRP were partially reduced using tris(2-carboxyethyl) phosphine (TCEP) under acidic conditions, followed by alkylation with N-ethylmaleimide (NEM). The procedure generated several isoforms with varying degrees of NEM alkylation. The multiple forms of Md65-AGRP generated by partial reduction and NEM modification were then completely reduced and carboxymethylated to identify unreactive disulfide bonds. Differentially labeled Md65-AGRP were directly sequenced and analyzed by MALDI mass spectrometry. The results confirmed that Md65-AGRP contained the same disulfide structure as that of Md5-AGRP reported previously [Bures, E. J., Hui, J. O., Young, Y. et al. (1998) Biochemistry 37, 12172-12177].

  14. [The influence of hyperleptinemia during pregnancy on fetal weight and obesity development in progeny mice with agouti yellow mutation].

    Science.gov (United States)

    Makarova, E N; Syracheva, M S; Bazhan, N M

    2014-03-01

    Maternal obesity increases the risk of obesity in the offspring, and obesity is accompanied by an increase in blood leptin levels. Leptin can influence the progeny metabolism via its influence on fetal growth and, possibly, via its action on AgRP expression in placenta. The "yellow" mutation at the mouse agouti locus (A(y)) evokes obesity and increases blood leptin levels in pregnant mice. The aim was to examine the influence of A(y) mutation in pregnant mice on fetal weight, placental expression of AgRP gene and food intake and obesity development in progeny. A(y) pregnant females as compared to control ones had increased circulating leptin levels on days 13 and 18 of pregnancy. Both fetal weight and placental expression of AgRP gene were increased on day 13 of pregnancy and decreased on day 18 of pregnancy in A(y) females as compared to control ones. Both control (a/a) and obesity prone (A(y)/a) male young born to A(y) mothers had lowered body weight and enhanced food intake between 5 and 11 weeks of age as compared to male progeny of control mothers. The enhanced leptin levels during pregnancy in mice are associated with retardation of obesity development in obesity prone male offspring and with changes in fetal weight and AgRP gene expression in placenta.

  15. Agouti Related Peptide Secreted Via Human Mesenchymal Stem Cells Upregulates Proteasome Activity in an Alzheimer’s Disease Model

    Science.gov (United States)

    Lee, Na Kyung; Park, Sang Eon; Kwon, Soo Jin; Shim, Sangmi; Byeon, Yeji; Kim, Jong-Hwa; Na, Duk L.; Chang, Jong Wook

    2017-01-01

    The activity of the ubiquitin proteasome system (UPS) is downregulated in aggregation diseases such as Alzheimer’s disease (AD). In this study, we investigated the therapeutic potential of the Agouti-related peptide (AgRP), which is secreted by human mesenchymal stem cells (MSCs), in terms of its effect on the regulation of proteasome activity in AD. When SH-SY5Y human neuroblastoma cells were co-cultured with MSCs isolated from human Wharton’s Jelly (WJ-MSC), their proteasome activity was significantly upregulated. Further analysis of the conditioned media after co-culture allowed us to identify significant concentrations of a neuropeptide, called AgRP. The stereotactic delivery of either WJ-MSCs or AgRP into the hippocampi of C57BL6/J and 5XFAD mice induced a significant increase of proteasome activity and suppressed the accumulation of ubiquitin-conjugated proteins. Collectively, these findings suggest strong therapeutic potential for WJ-MSCs and AgRP to enhance proteasome activity, thereby potentially reducing abnormal protein aggregation and delaying the clinical progression of various neurodegenerative diseases. PMID:28051110

  16. 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

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    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.

  17. LOBAÇÃO, ÁRVORE BRÔNQUICA E VASCULARIZAÇÃO ARTERIAL DO PULMÃO DA PACA (Agouti paca, LINAEUS, 1766 LOBATION, BRONCHIAL TREE AND ARTERIAL SUPPLY OF PACA LUNG (Agouti paca, LINAEUS, 1766

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    Márcia Rita Fernandes Machado

    2008-07-01

    Full Text Available

    Os pulmões são os principais órgãos do sistema respiratório, e o conhecimento morfológico da lobação, árvore brônquica e vascularização arterial torna-se imprescindível na prática clínica e cirúrgica. Os troncos pulmonares de dez pulmões de pacas foram injetados com látex e as peças fixadas em solução aquosa de formaldeído a 10%. Mediante dissecação, observou-se que, em 100% dos casos, o pulmão direito era constituído pelos lobos cranial, caudal, médio e acessório; o lobo médio era bilobado em partes cranial e caudal. O esquerdo possuía o lobo cranial, bilobado em partes cranial e caudal, lobo caudal e um pequeno lobo acessório. A artéria pulmonar direita emitia dois ramos para o lobo cranial, além dos ramos para as partes cranial e caudal do lobo médio, o ramo do lobo acessório e o do lobo caudal; a artéria pulmonar esquerda emitia dois ramos para a porção cranial e um para a porção caudal do lobo cranial; o lobo caudal esquerdo era irrigado pela continuação da artéria pulmonar esquerda, que emitia de cinco a seis ramos dorsais e de sete a oito ramos ventrais. Não houve variação nos pulmões estudados em relação aos lobos, nem no padrão de distribuição brônquica.

     

    PALAVRAS-CHAVE: Agouti paca, artéria pulmonar, pulmões, roedor

    Lungs are the main organs of the respiratory system and the morphological knowledge of lobation, bronchial tree and arterial vascularization becomes indispensable on clinics and surgery practice. The pulmonary trunks of 10 lungs were filled with latex and the anatomical sets were put in a 10% formaldehyde aqueous solution. By dissection, it was observed that, in 100% of the cases, the right lung was constituted by cranial, medium, caudal and accessory lobes. The medium lobe was divided into cranial and caudal portions. The left lung presented a cranial lobe

  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

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    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. Epistatic Interaction of the Melanocortin 1 Receptor and Agouti Signaling Protein Genes Modulates Wool Color in the Brazilian Creole Sheep.

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    Hepp, Diego; Gonçalves, Gislene Lopes; Moreira, Gilson Rudinei Pires; de Freitas, Thales Renato Ochotorena

    2016-11-01

    Different pigmentation genes have been associated with color diversity in domestic animal species. The melanocortin 1 receptor (MC1R), agouti signaling protein (ASIP), tyrosinase-related protein 1 (TYRP1), and v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) genes are candidate genes responsible for variation in wool color among breeds of sheep. Although the influence of these genes has been described in some breeds, in many others the effect of interactions among genes underlying wool color has not been investigated. The Brazilian Creole sheep is a local breed with a wide variety of wool color, ranging from black to white with several intermediate hues. We analyzed in this study the influence of the genes MC1R, ASIP, TYRP1, and KIT on the control of wool color in this breed. A total of 410 samples were analyzed, including 148 white and 262 colored individuals. The MC1R and ASIP polymorphisms were significantly associated with the segregation of either white or colored wool. The dominant MC1R allele (E(D) p.M73K and p.D121N) was present only in colored animals. All white individuals were homozygous for the MC1R recessive allele (E(+)) and carriers of the duplicated copy of ASIP A gene expression assay showed that only the carrier of the duplicated copy of ASIP produces increased levels in skin, not detectable in the single homozygous copy. These results demonstrate that the epistatic interaction of the genotypes in the MC1R and ASIP gene is responsible for the striking color variation in the Creole breed.

  20. Hypothalamic Agouti-Related Peptide mRNA is Elevated During Natural and Stress-Induced Anorexia.

    Science.gov (United States)

    Dunn, I C; Wilson, P W; D'Eath, R B; Boswell, T

    2015-09-01

    As part of their natural lives, animals can undergo periods of voluntarily reduced food intake and body weight (i.e. animal anorexias) that are beneficial for survival or breeding, such as during territorial behaviour, hibernation, migration and incubation of eggs. For incubation, a change in the defended level of body weight or 'sliding set point' appears to be involved, although the neural mechanisms reponsible for this are unknown. We investigated how neuropeptide gene expression in the arcuate nucleus of the domestic chicken responded to a 60-70% voluntary reduction in food intake measured both after incubation and after an environmental stressor involving transfer to unfamiliar housing. We hypothesised that gene expression would not change in these circumstances because the reduced food intake and body weight represented a defended level in birds with free access to food. Unexpectedly, we observed increased gene expression of the orexigenic peptide agouti-related peptide (AgRP) in both incubating and transferred animals compared to controls. Also pro-opiomelanocortin (POMC) mRNA was higher in incubating hens and significantly increased 6 days after exposure to the stressor. Conversely expression of neuropeptide Y and cocaine- and amphetamine-regulated transcript gene was unchanged in both experimental situations. We conclude that AgRP expression remains sensitive to the level of energy stores during natural anorexias, which is of adaptive advantage, although its normal orexigenic effects are over-ridden by inhibitory signals. In the case of stress-induced anorexia, increased POMC may contribute to this inhibitory role, whereas, for incubation, reduced feeding may also be associated with increased expression in the hypothalamus of the anorexigenic peptide vasoactive intestinal peptide.

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

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    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

  2. The high glycemic index diet was an independent predictor to explain changes in agouti-related protein in obese adolescents

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    Bárbara Dal Molin Netto

    2014-02-01

    Full Text Available The high glycemic index diet was an independent predictor to explain changes in agouti-related protein in obese adolescents. Background & Aims: The role of diet glycemic index (GI in the control of orexigenic and anorexigenic factors of the energy balance is still not clear. The present study aimed to assess whether the habitual diet, according to different GI foods, exerts influence on regulation of energy balance markers and the effects of interdisciplinary intervention in obese adolescents. Methods: A total of 55 obese adolescents, aged from 14 to 19 years, were submited to one year of interdisciplinary therapy and were divided in two groups, according to the predominant dietary pattern of food intake: high-GI group (H-GI; n = 29 and moderate/low-GI group (M/L-GI; n = 26. Results: The concentration of orexigenic factor AgRP (p < 0.01, visceral fat (p=0.04 and visceral/subcutaneous ratio (p = 0.03 were higher in the group of H-GI when compared with M/L-GI group. Moreover, the habitual consumption of H-GI foods was an independent predictor to explain changes in AgRP concentrations. After one year of interdisciplinary therapy, the adolescents presented significant reductions in body weight, total body fat (%, visceral and subcutaneous fat and HOMA-IR, as well as a significant increase of fat free mass (%. Conclusions: Our results may suggest that habitual H-GI diet could upregulate orexigenic pathways, contributing to vicious cycle between undesirable diets, deregulates energy balance and predispose to obesity. One the other hand, one year of interdisciplinary therapy can significant improves metabolic profile and central obesity in adolescents.

  3. Short-days induce weight loss in Siberian hamsters despite overexpression of the agouti-related peptide gene.

    Science.gov (United States)

    Jethwa, P H; Warner, A; Fowler, M J; Murphy, M; de Backer, M W; Adan, R A H; Barrett, P; Brameld, J M; Ebling, F J P

    2010-06-01

    Many vertebrates express profound annual cycles of body fattening, although it is not clear whether these represent differential activity of the central pathways known to mediate homeostatic control of food intake and energy expenditure, or whether the recent discovery of a major role for pars tuberalis-ependymal signalling points towards novel mechanisms. We examined this in the Siberian hamster (Phodopus sungorus) by using gene transfection to up-regulate a major orexigenic peptide, agouti-related peptide (AgRP), and then determined whether this increased anabolic drive could prevent the short-day induced winter catabolic state. Infusions of a recombinant adeno-associated virus encoding an AgRP construct into the hypothalamus of hamsters in the long-day obese phase of their seasonal cycle produced a 20% gain in body weight over 6 weeks compared to hamsters receiving a control reporter construct, reflecting a significant increase in food intake and a significant decrease in energy expenditure. However, all hamsters showed a significant, prolonged decrease in body weight when exposed to short photoperiods, despite the hamsters expressing the AgRP construct maintaining a higher food intake and lower energy expenditure relative to the control hamsters. Visualisation of the green fluorescent protein reporter and analysis of AgRP-immunoreactivity confirmed widespread expression of the construct in the hypothalamus, which was maintained for the 21-week duration of the study. In conclusion, the over-expression of AgRP in the hypothalamus produced a profoundly obese state but did not block the seasonal catabolic response, suggesting a separation of rheostatic mechanisms in seasonality from those maintaining homeostasis of energy metabolism.

  4. 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.

  5. Expression of melanocortin-4 receptor and agouti-related peptide mRNAs in arcuate nucleus during long term malnutrition of female ovariectomized rats

    OpenAIRE

    Fatemeh Sabet Sarvestani; Amin Tamadon; Aida Hematzadeh; Maliheh Jahanara; Mohammad Reza Jafarzadeh Shirazi; Ali Moghadam; Ali Niazi; Reza Moghiminasr

    2015-01-01

    Objective: Melanocortin-4 receptor (MC4R) and agouti-related peptide (AgRP) are involved in energy homeostasis in the rat. The aim of the present study was to evaluate the expression of MC4R and AgRP mRNAs in arcuate nucleus (ARC) during long term malnutrition of female ovariectomized rats. Materials and Methods: Ten female ovariectomized rats were divided into two equal groups (n=6) of normal and restricted diet groups. Using real-time PCR, the relative expressions (compared to controls) of ...

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

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    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.

  7. The high glycemic index diet was an independent predictor to explain changes in agouti-related protein in obese adolescents.

    Science.gov (United States)

    Dal Molin Netto, Bárbara; Landi Masquio, Deborah Cristina; Da Silveira Campos, Raquel Munhoz; De Lima Sanches, Priscila; Campos Corgosinho, Flavia; Tock, Lian; Missae Oyama, Lila; Túlio de Mello, Marco; Tufik, Sergio; Dâmaso, Ana Raimunda

    2014-02-01

    La Dieta de alto índice glucémico es un predictor independiente para explicar los cambios en la proteína relacionada al agouti en adolescentes obesos. Introducción y objetivos: El papel de la dieta de índice glucémico (GI) en el control de los factores orexigénicos y anorexígenos del balance de energía todavía no está claro. El presente estudio tuvo como objetivo evaluar si la dieta habitual, de acuerdo con diferentes alimentos con IG, ejerce influencia sobre la regulación de los marcadores del balance de energía y los efectos de la intervención interdisciplinaria en adolescentes obesos. Métodos: Un total de 55 adolescentes obesos, con edades de 14 a 19 años, han sido sometidos a un año de tratamiento interdisciplinario y se dividieron en dos grupos, de acuerdo al patrón de dieta predominante de la ingesta de alimentos: el grupo IG alto (H-GI; n = 29) y GI moderada/bajo grupo (M/L-GI, n = 26). Resultados: La concentración de orexigenic factor de AgRP (p adolescentes presentan una reducción significativa en el peso corporal, la grasa corporal total (%), visceral y la grasa subcutánea y el HOMA-IR, así como un aumento significativo de la masa libre de grasa (%). Conclusiones: Nuestros resultados pueden sugerir que la dieta H-GI habitual podría upregulate vías orexigénicos, contribuyendo al círculo vicioso entre las dietas indeseables, desregula el equilibrio energético y predisponen a la obesidad. Uno por otro lado, un año de tratamiento interdisciplinario puede perfil metabólico mejora significativa y la obesidad central en los adolescentes.

  8. Co-infections of the cestode Echinococcus vogeli and the nematode Calodium hepaticum in the hystricomorphic rodent Agouti paca from a forest reserve in Acre, Brazil.

    Science.gov (United States)

    Almeida, F; Caldas, R; Corrêa, C; Rodrigues-Silva, R; Siqueira, N; Machado-Silva, J R

    2013-12-01

    The helminth fauna of Agouti paca (Linnaeus, 1766) has seldom been studied. In this paper, we report an unusual mixed infection of Echinococcus vogeli Rausch & Bernstein, 1972 and Calodium hepaticum (syn. Capillaria hepatica Bancroft, 1863) in free-ranging paca from a forested region in Acre (Brazil). Gross morphological examination revealed that paca liver contained multiple spherical to subspherical white or translucent lesions, which were isolated or frequently contiguous and partially covered by Glisson's capsule. Microscopic examination revealed unilocular cystic structures that contained abundant brood capsules in which numerous protoscolices budded from the inner surface. The protoscolices possessed rostellar hooks (33-41 μm in length), a morphological characteristic of the blade and calcareous corpuscles that is consistent with the metacestode E. vogeli. The diagnosis of C. hepaticum infection was based on the morphology and morphometry of the egg-shaped ellipsoids with bipolar plugs (44.8 ± 1.9 μm (length) × 24.4 ± 2.0 μm (width)) and liver histopathology. This finding expands the known range of C. hepaticum hosts in South America and, to the best of our knowledge, it is the first case of a mixed infection of E. vogeli and C. hepaticum. Furthermore, our data provide evidence that wild animal meat may be a source of C. hepaticum infection.

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

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    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.

  10. [Annual follow-up of the gastrointestinal parasitosis of the tepezcuintle, Agouti paca (Rodentia: Agoutidae) in captivity in the Mexican tropic].

    Science.gov (United States)

    Ramírez-Herrera, O; Rodríguez-Vivas, R I; Montes-Pérez, R; Torres-Acosta, J F

    2001-01-01

    Previous 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 strategies against GIP in tepezcuintles under captivity. The objectives of the present study were to determine the prevalence of GIP orders and genera that infest tepezcuintles under captivity and, to describe the dynamics of faecal egg and oocyst excretion in a year. Ten tepezcuintles were sampled (faeces) twice every month for twelve months. The faecal samples were processed by the flotation and McMaster techniques. Two orders of parasites were determined: Strongylida and Eucoccidiida. Two genera of nematodes were also determined: Strongyloides and Trichuris. The prevalence of Strongylida eggs, Eucoccidiida oocysts and Trichuris sp. eggs reached 10-20% of animals in certain months. The most important genus was Strongyloides, found in 60 to 100% of the animals year round. The average excretion of eggs in the group was 45 to 372 eggs per gram. Tepezcuintles kept under captivity in Yucatan are parasited with Strongyloides sp throughout the year, but only occasionally had oocysts of Eucoccidiida and eggs of Strongylida and Trichuris sp.

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

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    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.

  12. Peroxisome Proliferator-Activated Receptor γ Controls Ingestive Behavior, Agouti-Related Protein, and Neuropeptide Y mRNA in the Arcuate Hypothalamus

    Science.gov (United States)

    Garretson, John T.; Teubner, Brett J.W.; Grove, Kevin L.; Vazdarjanova, Almira; Ryu, Vitaly

    2015-01-01

    Peroxisome proliferator-activated receptor γ (PPARγ) is clinically targeted for type II diabetes treatment; however, rosiglitazone (ROSI), a PPARγ agonist, increases food intake and body/fat mass as side-effects. Mechanisms for these effects and the role of PPARγ in feeding are not understood. Therefore, we tested this role in Siberian hamsters, a model of human energy balance, and C57BL/6 mice. We tested the following: (1) how ROSI and/or GW9662 (2-chloro-5-nitro-N-phenylbenzamide; PPARγ antagonist) injected intraperitoneally or into the third ventricle (3V) affected Siberian hamster feeding behaviors; (2) whether food deprivation (FD) co-increases agouti-related protein (AgRP) and PPARγ mRNA expression in Siberian hamsters and mice; (3) whether intraperitoneally administered ROSI increases AgRP and NPY in ad libitum-fed animals; (4) whether intraperitoneally administered PPARγ antagonism blocks FD-induced increases in AgRP and NPY; and finally, (5) whether intraperitoneally administered PPARγ modulation affects plasma ghrelin. Third ventricular and intraperitoneally administered ROSI increased food hoarding and intake for 7 d, an effect attenuated by 3V GW9662, and also prevented (intraperitoneal) FD-induced feeding. FD hamsters and mice increased AgRP within the arcuate hypothalamic nucleus with concomitant increases in PPARγ exclusively within AgRP/NPY neurons. ROSI increased AgRP and NPY similarly to FD, and GW9662 prevented FD-induced increases in AgRP and NPY in both species. Neither ROSI nor GW9662 affected plasma ghrelin. Thus, we demonstrated that PPARγ activation is sufficient to trigger food hoarding/intake, increase AgRP/NPY, and possibly is necessary for FD-induced increases in feeding and AgRP/NPY. These findings provide initial evidence that FD-induced increases in AgRP/NPY may be a direct PPARγ-dependent process that controls ingestive behaviors. PMID:25788674

  13. Lipopolysaccharide (LPS) and tumor necrosis factor alpha (TNFα) blunt the response of Neuropeptide Y/Agouti-related peptide (NPY/AgRP) glucose inhibited (GI) neurons to decreased glucose.

    Science.gov (United States)

    Hao, Lihong; Sheng, Zhenyu; Potian, Joseph; Deak, Adam; Rohowsky-Kochan, Christine; Routh, Vanessa H

    2016-10-01

    A population of Neuropeptide Y (NPY) neurons which co-express Agouti-related peptide (AgRP) in the arcuate nucleus of the hypothalamus (ARC) are inhibited at physiological levels of brain glucose and activated when glucose levels decline (e.g. glucose-inhibited or GI neurons). Fasting enhances the activation of NPY/AgRP-GI neurons by low glucose. In the present study we tested the hypothesis that lipopolysaccharide (LPS) inhibits the enhanced activation of NPY/AgRP-GI neurons by low glucose following a fast. Mice which express green fluorescent protein (GFP) on their NPY promoter were used to identify NPY/AgRP neurons. Fasting for 24h and LPS injection decreased blood glucose levels. As we have found previously, fasting increased c-fos expression in NPY/AgRP neurons and increased the activation of NPY/AgRP-GI neurons by decreased glucose. As we predicted, LPS blunted these effects of fasting at the 24h time point. Moreover, the inflammatory cytokine tumor necrosis factor alpha (TNFα) blocked the activation of NPY/AgRP-GI neurons by decreased glucose. These data suggest that LPS and TNFα may alter glucose and energy homeostasis, in part, due to changes in the glucose sensitivity of NPY/AgRP neurons. Interestingly, our findings also suggest that NPY/AgRP-GI neurons use a distinct mechanism to sense changes in extracellular glucose as compared to our previous studies of GI neurons in the adjacent ventromedial hypothalamic nucleus.

  14. Seed dispersal and spatial distribution of Attalea geraensis (Arecaceae) in two remnants of Cerrado in Southeastern Brazil

    Science.gov (United States)

    Bonjorne de Almeida, Lilian; Galetti, Mauro

    2007-09-01

    The seed dispersal system of Attalea geraensis (Arecaceae), an acaulescent palm, was investigated during one year in two Cerrado fragments in the state of São Paulo, southeastern Brazil. A. geraensis had inflorescences and infrutescences throughout the year. Two scatter-hoarding rodents (the spiny rat, Clyomys bishopi and agoutis, Dasyprocta azarae) were identified as seed predators/dispersers, able to move seeds up to 30 m from the palms, although most of the fruits (57.5%) were dispersed less than 2 m. The removal rates were high and after 20 days, 97.2% of the fruits were removed. Fruit fate was not related to fruit mass, length and diameter. The application of Morisita's index showed a more clumped distribution of adults in the smaller fragment, probably because of the absence of agoutis. Higher seed removal by rodents in the large Cerrado remnant may decrease seed predation by beetles.

  15. An Autochthonous Case of Echinococcus vogeli Rausch & Bernstein, 1972 Polycystic Echinococcosis in the State of Rondônia, Brazil

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    Rosângela Rodrigues-Silva

    2002-01-01

    Full Text Available The present case report refers to a patient from the State of Rondônia, North region of Brazil, attended with clinical suspicion of hepatic echinococcosis. Examination by imaging (ultrasonography and computerized tomography revealed a conglomerate of cystic lesions, with mobile contents within the cyst. The serology (immunoblot for Echinococcus sp. was positive (21 and 31 kDa bands. This case is the first reported in Rondônia, suggesting the need to investigate the polycystic echinococcosis in individuals with hepatic cysts from areas of tropical forest and hunting habits where wild life was present as wild dogs, cats and rodents, particularly Agouti paca (paca and Dasyprocta aguti (agouti.

  16. 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

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

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    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

  18. 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

  19. 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.

  20. Agouti-related protein prevents self-starvation

    NARCIS (Netherlands)

    Kas, M J H; van Dijk, G; Scheurink, A J W; Adan, R A H

    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

  1. Effects of Electro-acupuncture on Insulin Resistance and Hypothalamic Agouti Gene-related Protein and Neuropeptide Y in Obesity Rats%电针对单纯性肥胖大鼠胰岛素抵抗及下丘脑刺鼠基因相关蛋白、神经肽Y的影响

    Institute of Scientific and Technical Information of China (English)

    刘霞; 何军锋; 屈娅婷; 刘志君; 蒲庆阳; 郭胜童; 杜佳; 蒋鹏飞

    2016-01-01

    目的:观察电针对饮食诱导的单纯性肥胖大鼠体质量、胰岛素抵抗及下丘脑刺鼠基因相关蛋白(AGRP)、神经肽Y(NPY)基因表达的影响,探讨电针治疗肥胖症的相关机制。方法50只SD雄性大鼠随机分为低脂组10只和高脂组40只,高脂组大鼠造模成功后,随机分为模型组、电针组、西药组,每组10只。电针组电针“后三里”和“曲池”,每日1次,每次20 min,连续28 d;西药组予奥利司他灌胃,低脂组和模型组不做治疗。每日记录大鼠体质量,检测空腹血糖和胰岛素,RT-qPCR检测下丘脑AGRP和NPY基因表达水平,HE染色观察脂肪组织和肝脏形态。结果治疗后电针组和西药组体质量、胰岛素抵抗指数、AGRP、NPY、脂肪细胞直径均低于模型组(P<0.05),2组比较差异无统计学意义。电针组和西药组肝脏脂变情况均得到改善。结论电针通过改善胰岛素抵抗,抑制NPY和AGRP神经元的表达,达到控制体质量增长的目的。%Objective To observe the effects of electro-acupuncture (EA) on body weight, insulin resistance, hypothalamic agouti gene-related protein (AGRP) and neuropeptide Y (NPY) in diet induced obesity (DIO) rats; To discuss its mechanism for DIO.Methods Fifty SD male rats were randomly divided into low fat diet groups (LFD) and high fat diet group. After the DIO models were established, the successful model rats were randomly divided into model group, EA group and Orlistat (OLST) group. EA was applied to “Zusanli” (ST36) and “Quchi” (LI11) for 20 minutes. The treatment was done once a day for 28 days. OLST was treated with orlistat by gavage. LFD and model did not receive treatment. Body weight was recorded every day. FPG and FINS were detected. The expressions of AGRP and NPY were detected by RT-QPCR. Morphological changes of adipocyte and liver were examined by HE staining.Results The body weight, HOMA-IR, AGRP, NPY and

  2. The roles of ghrelin/agouti-related protein/peptide YY signal pathway in gastric bypass operation for type 2 diabetes%胃饥饿素/肽YY/刺鼠相关蛋白信号在胃旁路手术治疗2型糖尿病中的作用

    Institute of Scientific and Technical Information of China (English)

    高寅生; 侯亚勃; 杨晓军; 高鹏; 曹农

    2016-01-01

    Objective To study the roles of ghrelin,agouti-related protein (AGRP) and peptide YY (PYY) signal in treatment of type 2 diabetes mellitus by gastric bypass operation.Methods Twenty adult SD rats were used to establish the model of type 2 diabetes mellitus,and divided into 2 groups:No operation group (NO,n =10) and Roux-en-Y gastric bypass operation group (RYGB,n =10),and another ten adult rats were used as the Normal Control group (NC,n =10).The RYGB group were performed operation after the rat model of type 2 diabetes mellitus were established successfully.The blood were separately collected to examine ghrelin,blood sugar,cholesterol and triglyceride before and after operation,and we monitored the consumption of food and water everyday.The hypothalamus tissues were collected at the 4th week after operation to examine the expression of AGRP and PYY mRNA.Results At the 4th week after operation,the blood sugar dropped to (6.18 ±0.77) mmol/L,Triglycerides dropped to (2.45 ±0.23) mmol/L;Cholesterol dropped to (2.07 ± 0.22) mmoL/L and the consumption of food,water of RYGB group were nearly down to normal level.The level of ghrelin dropped to (410.60 ± 58.33) ng/L,AGRP mRNA dropped to 0.80 ±0.13 in hypothalamus were lower than NO group after operation,the level of PYY mRNA rised to 1.60 ± 0.25 were significantly increased (P < 0.05).Conclusion We can conclude that the situation of type 2 diabetes mellitus can be controlled by Roux-en-Y gastric bypass operation.Ghrelin may regulate the energy metabolism of type 2 diabetes mellitus via AGRP and PYY signals.Our results suggest that the roles of ghrelin,AGRP and PYY signals may play an important role in the control of type 2 diabetes mellitus after Roux-en-Y gastric bypass operation.%目的 探讨胃饥饿素(Ghrelin)、肽YY(PYY)、刺鼠相关蛋白(AGRP)信号通路在胃旁路手术治疗2型糖尿病中的作用及其机制.方法 采用20只成年SD雄性大鼠成功建立2型糖尿病大鼠模型,随机分

  3. Mammal Hunting in the Special Use Zone and Buffer Tingo Maria National Park, Huánuco, Peru

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    Fiorella Nasha Gonzales Guillén

    2014-12-01

    Full Text Available Between the months of August to November 2011 were conducted 42 semi-structured interviews to assess the hunting of mammals in areas of special purpose (ZUE and buffer (ZA National Park Tingo María surveys. The results indicate that 43% of the population practiced hunting as a secondary activity, the main smallholder agriculture. The methodology used for hunting are the "tramperas" while the hunting is often 2-3 times a month. Hunting is more common after the wet season, it is selective and responds to the taste of meat that an economic need. Among the most hunted mammals include agouti Dasyprocta sp. and picuro Cuniculus paca, while animals higher biomass as the peccary Pecari tajacu are rare in the area, so it is recommended to increase the control of hunting of vulnerable species in the villages which are inside and in the vicinity of the Park.

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

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    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.

  5. Genetic Effect of Tyrosinase (TYR), Microphthalmia-associated Transcription Factor (MITF) and Agouti Signaling Protein (ASIP) Genes on Melanin Deposition of White Silky Fowl (Gallus gallus domesticus Brisson)%酪氨酸酶(TYR)、小眼畸形相关转录因子(MITF)和刺鼠信号蛋白(ASIP)基因对白绒乌骨鸡黑色素沉积的遗传效应

    Institute of Scientific and Technical Information of China (English)

    郑嫩珠; 李丽; 辛清武; 缪中纬; 朱志明; 陈黎; 刘凤辉; 吴剑飞; 黄勤楼

    2015-01-01

    为研究白绒乌骨鸡(Gallus gallus domesticus Brisson)黑色素沉积分子机制,本研究采用实时荧光定量PCR(quantitative Real-time PCR,qRT-PCR)的2-△△Ct检测酪氨酸酶(tyrosinase,TYR)、刺鼠信号蛋白(agouti signaling protein,ASIP)和小眼畸形相关转录因子(microphthalmia-associated transcription factor,MITF)基因在乌骨鸡皮肤、肌肉、肝脏、肾脏和肌胃的表达情况,采用紫外分光光度法测定不同组织黑色素含量,探索3个基因在不同组织中mRNA表达量与黑色素沉积之间的关系.结果表明,TYR、MITF和ASIP在所有组织中均有表达,且各基因mRNA相对表达量在各组织间差异极显著(P<0.01),其中MITF和TYR mRNA表达量依次为皮肤>肾脏>肌胃>肝脏>肌肉,与乌骨鸡各组织黑色素沉积规律基本一致;ASIP基因表达量则与其相反,表现为肌肉>肝脏>肌胃>肾脏>皮肤.相关性分析表明,TYR和MITF基因在各个组织中的表达量与其黑色素含量呈显著正相关(P<0.05),ASIP基因表达量与其呈显著负相关(P<0.05).由此提示,TYR、MITF和ASIP与白绒乌骨鸡黑色素沉积均具有一定的相关性,其中TYR和MITF基因的高表达可能促进乌骨鸡黑色素沉积,ASIP则相反.本研究为进一步阐明黑色素沉积的遗传调控机制提供了理论基础.

  6. Seed dispersal, plant recruitment and spatial distribution of Bactris acanthocarpa Martius (Arecaceae) in a remnant of Atlantic forest in northeast Brazil

    Science.gov (United States)

    Silva, Maria G.; Tabarelli, Marcelo

    2001-12-01

    Seed dispersal ecology of Bactris acanthocarpa Mart. (Arecaceae), an Atlantic forest understory palm, was investigated during two years as an attempt to test the following predictions: (i) seeds of Bactris are dispersed by mammals and large-gaped birds; (ii) Bactris benefits from seed dispersal in terms of seed predation avoidance, improvement of seed germination and seedling survival; and (iii) spatial distribution of adults is related to patterns of seed dispersal. The study was conducted at Dois Irmãos Reserve, a 387.4-ha reserve of Atlantic forest in northeastern Brazil (8º S-35º W). Black-rumped agoutis ( Dasyprocta prymnolopha) and Guianan squirrels ( Sciurus aestuans) were identified as the seed dispersers/predators, moving seeds short distances ( 4 m away in contrast to 96% of seedlings that occurred concentrated within 4 m from adults (77% under the palm crowns). Here, we present evidence that spatial distribution of B. acanthocarpa is partly due to low rates of seed removal, short-distance seed dispersal by agoutis and squirrels, and early seedling mortality associated with presence of seedlings under palm crowns.

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

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    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.

  8. 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.

  9. 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

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

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    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

  11. A survey of hemoparasite infections in free-ranging mammals and reptiles in French Guiana.

    Science.gov (United States)

    de Thoisy, B; Michel, J C; Vogel, I; Vié, J C

    2000-10-01

    Blood smears of 1,353 free-ranging mammals (35 species) and 112 reptiles (31 species) from French Guiana were examined for hemoparasites. Parasites from 3 major groups were recorded: Apicomplexa (including hemogregarines, piroplasms, and Plasmodium spp.), Trypanosomatidae, and Filaroidea. Fifty percent of the individuals (86% of the species) were infected by parasites from at least 1 group. Hemogregarines, identified as Hepatozoon sp., infected numerous snakes with high prevalences (30-100%); infection is reported for the first time in 5 host genera of snakes: Clelia, Oxybelis, Pseustes, Rhinobotryum, and Bothriopsis. Infections were also observed in 4 marsupial species and 1 rodent. Hepatozoon spp. recorded in Didelphis albiventris (Marsupialia) and Coendou prehensilis (Rodentia) may be new species. Plasmodium sp. were observed in 2 snake species, Dipsas indica (Colubridae) and Bothrops atrox (Viperidae). Plasmodium brasilianum was recorded in all 5 primate species examined. Piroplasms were observed in all mammal orders except primates. Large terrestrial rodents were the main hosts of members of the Babesidae; 42% of Myoprocta acouchy, 36% of Dasyprocta agouti, and 44% of Agouti paca were infected. Trypanosomes were common in mammals and were recorded in 70% of the examined genera. Trypanosoma cruzi-like infections were reported in 21 mammal species, including sloths, rodents, carnivores, and primates. Microfilariae were also widespread, with higher prevalences in sloths, anteaters, and porcupines (>40% of the individuals infected) and in tamarins (95% infected). This survey highlights some potential anthropozoonotic risks due to the recent further evidence of Plasmodium brasilianum and P. malariae as a single species and to the increased diversity of hosts for Trypanosoma cruzi.

  12. 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

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

    Science.gov (United States)

    Chinchilla, Federico A

    2009-09-01

    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.

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

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    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

  15. PESO PÓS-PARTO, FREQÜÊNCIA E PREVALÊNCIA DO TIPO DE PARTO DE CUTIAS (Dasyprocta sp CRIADAS EM CATIVEIRO

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    Maria Acelina Martins de Carvalho

    2006-10-01

    Full Text Available A pesquisa objetivou avaliar parâmetros de desenvolvimento de cutias, buscando fornecer dados para contribuir com a seleção, o melhoramento genético e formas adequadas de manejo para estes animais. Foram observados o peso pós-parto, freqüência e a prevalência do tipo de parto em função da época do ano em 33 fêmeas. Constatou-se que não houve interação entre época do ano e tipo de parto (P>0,05. O peso médio pós-parto foi de 2,24 Kg e 2,39 Kg, para o período de janeiro a dezembro, respectivamente, não apresentando diferença significativa para esta variável (P>0,05. Com relação ao tipo de parto, as cutias com parto simples apresentaram peso médio de 2,32 Kg e as com parto duplo 2,38 Kg, não sendo estes valores significativamente diferentes entre si (P>0,05. Concluiu-se que o peso da cutia fêmea pós-parto, a freqüência e o tipo de parto (simples e duplos não sofrem influência da época do ano e que a cutia em cativeiro se comporta como poliéstrica contínua. PALAVRAS-CHAVE: Cutia, peso pós-parto, prevalência, tipo de parto.

  16. Rhizobium grahamii sp. nov., from nodules of Dalea leporina, Leucaena leucocephala and Clitoria ternatea, and Rhizobium mesoamericanum sp. nov., from nodules of Phaseolus vulgaris, siratro, cowpea and Mimosa pudica.

    Science.gov (United States)

    López-López, Aline; Rogel-Hernández, Marco A; Barois, Isabelle; Ortiz Ceballos, Angel I; Martínez, Julio; Ormeño-Orrillo, Ernesto; Martínez-Romero, Esperanza

    2012-09-01

    Two novel related Rhizobium species, Rhizobium grahamii sp. nov. and Rhizobium mesoamericanum sp. nov., were identified by a polyphasic approach using DNA-DNA hybridization, whole-genome sequencing and phylogenetic and phenotypic characterization including nodulation of Leucaena leucocephala and Phaseolus vulgaris (bean). As similar bacteria were found in the Los Tuxtlas rainforest in Mexico and in Central America, we suggest the existence of a Mesoamerican microbiological corridor. The type strain of Rhizobium grahamii sp. nov. is CCGE 502(T) (= ATCC BAA-2124(T) = CFN 242(T) = Dal4(T) = HAMBI 3152(T)) and that of Rhizobium mesoamericanum sp. nov. is CCGE 501(T) (= ATCC BAA-2123(T) = HAMBI 3151(T) = CIP 110148(T) = 1847(T)).

  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

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    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. Vascular organization of the hystricomorph placenta: a comparative study in the agouti, capybara, guinea pig, paca and rock cavy.

    Science.gov (United States)

    Miglino, M A; Carter, A M; Ambrosio, C E; Bonatelli, M; De Oliveira, M F; Dos Santos Ferraz, R H; Rodrigues, R F; Santos, T C

    2004-05-01

    The placental vasculature of five hystricomorph rodents was examined by latex injection of the blood vessels, immunohistochemistry and scanning electron microscopy of vessel casts. The pattern of branching of the vessels is described at the level of fine structure. The placenta is divided into lobes separated by interlobular trophoblast. Fetal arteries course through the interlobular areas and give rise to capillaries from which blood drains into veins at the centre of the lobes. Maternal blood reaches the placenta through spiral arteries that pass around the perimeter of the subplacenta. They supply large maternal blood sinuses, lined by trophoblast, which run through the interlobular areas and into the centre of the lobes. Here they supply fine channels that run parallel to the fetal capillaries, so that maternal blood flows from the centre of the lobe to the periphery. This arrangement provides the morphological basis for countercurrent exchange. The maternal channels of the labyrinth drain into spaces formed by the latticework of the interlobular trophoblast and thence through venous lacunae to a basal venous lacunar ring. The subplacenta is supplied by a single fetal artery. The vessels within the subplacenta pursue a tortuous course with dilatations and constrictions as in an endocrine gland.

  19. 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

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    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

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

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    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.

  1. Infecções experimentais na Leishmaniose Tegumentar Americana

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    Aristides Marques da Cunha

    1944-10-01

    Full Text Available Rhésus foram infectados com culturas recentemente isoladas de L. brasiliensis. As inoculações foram feitas por via intradérmica nas arcadas superciliares e, excepcionalmente, na superfícia do nariz. O prazo da incubação foi de 1 a 2 mêses. A marcha da infecção varia conforme as lesões se limitam à pele ou se estendem às mucosas. No primeiro caso, a duração da infecção foi de 3 a 8 meses e terminou sempre pela cura espontânea. Quando as lesões se estendem às mucosas elas persistem e se agravam, enquanto as lesões cutâneas observadas no mesmo animal, regridem, tendendo para cicatrização e cura. Cães também foram injetados com resultados positivos. As inoculações foram praticadas por via intradérmica na superfície do nariz. O prazo de incubação foi de cêrca de 2 mêses e as lesões observadas se limitaram à pele e terminaram pela cura. Uma cotia (Dasyprocta agouti foi inoculada não se mostrando infectada. Um rhésus, curado de uma infecção pela L. brasiliensis, inoculado de novo com outra amostra do mesmo parasito, não se mostrou infectado. A extensão das lesões às mucosas nas infecções experimentais do rhésus pela L. brasiliensis, fato ainda não veificado na L. trópica, constitue mais um argumento em favor da independência daquela espécie.Rhesus specimens were infected with recently isolated cultures of L. brasiliensis. The inoculations were made intradermically into the superciliary arches and, exceptionally, into the skin of the nose. The incubation period from 1 to 2 months. The course of the infection varies according to the extention of the lesios if limited to the skin of invading the mucous membranes. In the first case, the infection lasted form 3 to 8 months and always termninated in spontaneous cure. When the changes extend to the mucous membranes, they persist and evolute, whilst the skin changes observed on the same animal become regressive and tending towards cicatrization and cure. Also

  2. 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

  3. 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.

  4. Effects of Portabella mushrooms on collagen-induced arthritis, inflammatory cytokines, and body composition in dilute brown non-agouti (DBA1 mice

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    Stanley A. Lightfoot

    2011-09-01

    Full Text Available Background:Exotic mushrooms have long been used in Asia for treatment and/or prevention of chronic diseases due to their immunomodulatory properties. However, the health benefits of portabella mushrooms (PM (brown Agaricus bisporous, on collagen-induced arthritis (CIA and associated complications, (i.e. loss of lean mass, increased fat mass and inflammatory cytokines, have not been previously investigated.Methods:We investigated CIA pathogenesis, body composition and plasma levels of IL- 6, TNF-α and sICAM1 in DBA1 female mice fed either the AIN76 diet or the same diet fortified with 5% lyophilized PM (n=19-20/group. Ten mice/group were immunized with 100 μg bovine collagen type II on day 42 of the protocol, followed by 50 μg lipopolysaccharides on day 62, and euthanized on day 73-74. Cytokines were measured by ELISA.Results:Compared to baseline diet, PM had: no protective effect from CIA since all collagen-immunized mice developed severe edema, bone erosion, and mononuclear cell infiltration in paws. In mice with and those without CIA, feeding a PM-fortified diet resulted in higher percent of body fat than feeding the baseline diet (p<0.05. After CIA induction, PM provided the followingFunctional Foods in Health and Disease 2011; 9:279-296beneficial effects: (a a smaller reduction in lean mass and absolute thymus weight; (b a higher fat mass loss; and (c lower plasma TNF-α levels (p <0.05. PM-fortification did not alter plasma IL-6 and sICAM1 regardless of CIA status; but it increased in vitro IL-6 secretion by mitogen-treated spleen cells.Conclusion:Our data suggest that PM may reduce plasma TNF-α, attenuate lean mass loss and thymus atrophy associated with arthritis, and protect spleen cell function assessed by IL-6 secretion. However, PM-fortification did not attenuate overall CIA pathogenesis which may be due to lack of effect on plasma IL-6. Decreased TNF-α without alterations in IL-6 may reduce the risk of other conditions associated with chronic inflammation such as cardiovascular disease.

  5. 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

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    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

  6. Epigenetic’s role in fish pigmentation

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    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.

  7. The importance of pollen chemistry in evolutionary host shifts of bees

    Science.gov (United States)

    Vanderplanck, Maryse; Vereecken, Nicolas J.; Grumiau, Laurent; Esposito, Fabiana; Lognay, Georges; Wattiez, Ruddy; Michez, Denis

    2017-01-01

    Although bee-plant associations are generally maintained through speciation processes, host shifts have occurred during evolution. Understanding shifts between both phylogenetically and morphologically unrelated plants (i.e., host-saltation) is especially important since they could have been key processes in the origin and radiation of bees. Probably far from being a random process, such host-saltation might be driven by hidden constraints associated with plant traits. We selected two clades of oligolectic bees (i.e., Colletes succinctus group and Melitta leporina group) foraging on co-flowering but unrelated host-plants to test this hypothesis. We analyzed floral scent, floral color and chemical composition of pollen from host and non-host plants of these two clades. We did not find evidence for host-plant evolution in the Melitta leporina group driven by one of the assayed floral traits. On the contrary, hosts of the C. succinctus group display similar primary nutritive content of pollen (i.e., amino acids and sterols) but not similar floral scent or color, suggesting that shared pollen chemistry probably mediates saltation in this clade. Our study revealed that constraints shaping floral associations are diverse and clearly depend on species life-history traits, but evidence suggests that pollen chemistry may act as a major floral filter and guide evolutionary host-shifts. PMID:28216663

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

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    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.

  9. The mouse pink-eyed dilution allele of the P-gene greatly inhibits eumelanin but not pheomelanin synthesis.

    Science.gov (United States)

    Hirobe, Tomohisa; Ito, Shosuke; Wakamatsu, Kazumasa

    2011-02-01

    The mouse pink-eyed dilution (p) locus is known to control eumelanin synthesis, melanosome morphology, and tyrosinase activity in melanocytes. However, it has not been fully determined whether the mutant allele, p affects pheomelanin synthesis. Effects of the p allele on eumelanin and phemelanin synthesis were investigated by chemical analysis of dorsal hairs of 5-week-old mice obtained from the F(2) generations (black, pink-eyed black, recessive yellow, pink-eyed recessive yellow, agouti, and pink-eyed agouti) between C57BL/10JHir (B10)-congenic pink-eyed black mice (B10-p/p) and recessive yellow (B10-Mc1r(e)/Mc1r(e)) or agouti (B10-A/A) mice. The eumelanin content was dramatically (>20-fold) decreased in pink-eyed black and pink-eyed agouti mice, whereas the pheomelanin content did not decrease in pink-eyed black, pink-eyed recessive yellow, or pink-eyed agouti mice compared to the corresponding P/- mice. These results suggest that the pink-eyed dilution allele greatly inhibits eumelanin synthesis, but not pheomelanin synthesis.

  10. Genotype-dependent participation of coat color gene loci in the behavioral traits of laboratory mice.

    Science.gov (United States)

    Yamamuro, Yutaka; Shiraishi, Aya

    2011-10-01

    To evaluate if loci responsible for coat color phenotypes contribute to behavioral characteristics, we specified novel gene loci associated with social exploratory behavior and examined the effects of the frequency of each allele at distinct loci on behavioral expression. We used the F2 generation, which arose from the mating of F1 mice obtained by interbreeding DBA/2 and ICR mice. Phenotypic analysis indicated that the agouti and albino loci affect behavioral traits. A genotype-based analysis revealed that novel exploratory activity was suppressed in a manner dependent on the frequency of the dominant wild-type allele at the agouti, but not albino, locus. The allele-dependent suppression was restricted to colored mice and was not seen in albino mice. The present results suggest that the agouti locus contributes to a particular behavioral trait in the presence of a wild-type allele at the albino locus, which encodes a structural gene for tyrosinase.

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

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    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.

  12. Apolipoprotein A-IV inhibits AgRP/NPY neurons and activates POMC neurons in the arcuate nucleus

    Science.gov (United States)

    Apolipoprotein A-IV (apoA-IV) in the brain potently suppresses food intake. However the mechanisms underlying its anorexigenic effects remain to be identified. We first examined the effects of apoA-IV on cellular activities in hypothalamic neurons that co-express agouti-related peptide (AgRP) and ne...

  13. Simultaneous gene editing by injection of mRNAs encoding transcription activator-like effector nucleases into mouse zygotes.

    Science.gov (United States)

    Li, Chunliang; Qi, Rong; Singleterry, Rebecca; Hyle, Judith; Balch, Amanda; Li, Xiuling; Sublett, Jack; Berns, Hartmut; Valentine, Marcus; Valentine, Virginia; Sherr, Charles J

    2014-05-01

    Injection of transcription activator-like effector nucleases (TALEN) mRNAs into mouse zygotes transferred into foster mothers efficiently generated founder mice with heritable mutations in targeted genes. Immunofluorescence visualization of phosphorylated histone 2A (γH2AX) combined with fluorescence in situ hybridization revealed that TALEN pairs targeting the Agouti locus induced site-directed DNA breaks in zygotes within 6 h of injection, an activity that continued at reduced efficiency in two-cell embryos. TALEN-Agouti mRNAs injected into zygotes of brown FvB × C57BL/6 hybrid mice generated completely black pups, confirming that mutations were induced prior to, and/or early after, cell division. Founder mice, many of which were mosaic, transmitted altered Agouti alleles to F1 pups to yield an allelic series of mutant strains. Although mutations were targeted to "spacer" sequences flanked by TALEN binding sites, larger deletions that extended beyond the TALEN-binding sequences were also detected and were similarly inherited through the germ line. Zygotic coinjection of TALEN mRNAs directed to the Agouti, miR-205, and the Arf tumor suppressor loci yielded pups containing frequent and heritable mutations of two or three genes. Simultaneous gene editing in zygotes affords an efficient approach for producing mice with compound mutant phenotypes, bypassing constraints of conventional mouse knockout technology in embryonic stem cells.

  14. Central melanocortins regulate the motivation for sucrose reward

    NARCIS (Netherlands)

    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

  15. Dynamic reprogramming of DNA methylation at an epigenetically sensitive allele in mice.

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    Marnie E Blewitt

    2006-04-01

    Full Text Available There is increasing evidence in both plants and animals that epigenetic marks are not always cleared between generations. Incomplete erasure at genes associated with a measurable phenotype results in unusual patterns of inheritance from one generation to the next, termed transgenerational epigenetic inheritance. The Agouti viable yellow (A(vy allele is the best-studied example of this phenomenon in mice. The A(vy allele is the result of a retrotransposon insertion upstream of the Agouti gene. Expression at this locus is controlled by the long terminal repeat (LTR of the retrotransposon, and expression results in a yellow coat and correlates with hypomethylation of the LTR. Isogenic mice display variable expressivity, resulting in mice with a range of coat colours, from yellow through to agouti. Agouti mice have a methylated LTR. The locus displays epigenetic inheritance following maternal but not paternal transmission; yellow mothers produce more yellow offspring than agouti mothers. We have analysed the DNA methylation in mature gametes, zygotes, and blastocysts and found that the paternally and maternally inherited alleles are treated differently. The paternally inherited allele is demethylated rapidly, and the maternal allele is demethylated more slowly, in a manner similar to that of nonimprinted single-copy genes. Interestingly, following maternal transmission of the allele, there is no DNA methylation in the blastocyst, suggesting that DNA methylation is not the inherited mark. We have independent support for this conclusion from studies that do not involve direct analysis of DNA methylation. Haplo-insufficiency for Mel18, a polycomb group protein, introduces epigenetic inheritance at a paternally derived A(vy allele, and the pedigrees reveal that this occurs after zygotic genome activation and, therefore, despite the rapid demethylation of the locus.

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

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    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.

  17. Arborescent palm seed morphology and seedling distribution.

    Science.gov (United States)

    Salm, Rodolfo

    2005-11-01

    This study examines how the seed morphology of two large arborescent palms, Attalea maripa (Aubl.) Mart. and Astrocaryum aculeatum G. Mey, may affect their seed shadow in a seasonally dry Amazonian forest. In addition to being smaller and produced in larger numbers than those of A. aculeatum, A. maripa seeds also presented a substantially lower amount of nutritional reserves available for the embryo. However, A. maripa seedlings were found in much higher numbers than those of A. aculeatum. The results suggest that, within the spatial scale considered, the seed rain of A. maripa is more restricted to the area surrounding around reproductive conspecifics than that of A. aculeatum. Furthermore, in comparison with those of A. aculeatum, the smaller seeds of A. maripa might be less attractive to scatterhoarding rodents (e.g. Dasyprocta aguti). The pattern observed emphasizes the importance of scatterhoarding rodents as dispersers of large-seeded plant species in Neotropical forests.

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

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    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.

  19. Arborescent palm seed morphology and seedling distribution

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    Rodolfo Salm

    Full Text Available This study examines how the seed morphology of two large arborescent palms, Attalea maripa (Aubl. Mart. and Astrocaryum aculeatum G. Mey, may affect their seed shadow in a seasonally dry Amazonian forest. In addition to being smaller and produced in larger numbers than those of A. aculeatum, A. maripa seeds also presented a substantially lower amount of nutritional reserves available for the embryo. However, A. maripa seedlings were found in much higher numbers than those of A. aculeatum. The results suggest that, within the spatial scale considered, the seed rain of A. maripa is more restricted to the area surrounding around reproductive conspecifics than that of A. aculeatum. Furthermore, in comparison with those of A. aculeatum, the smaller seeds of A. maripa might be less attractive to scatterhoarding rodents (e.g. Dasyprocta aguti. The pattern observed emphasizes the importance of scatterhoarding rodents as dispersers of large-seeded plant species in Neotropical forests.

  20. Fatty acids composition of fruits of selected Central European sedges (Carex L. Cyperaceae

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    Janyszek, Magdalena

    2010-06-01

    Full Text Available Fatty acids in the fruits of 13 sedge species (Carex L., Cyperaceae were analyzed. The oil contents in the fruits of the studied sedges ranged from 3.73 and 46.52%. In the studied fruit oils 14 different fatty acids were identified. The main unsaturated fatty acids were: linoleic, α-linolenic, oleic, oleopalmitic n-7; oleopalmitic n-9, octadecenic, and eicosenoic acids. The following acids were found in the greatest quantities: linoleic, oleic, α-linolenic and palmitic acids. Based on the fatty acid composition, studied taxa can be divided in two groups. The first group (C. flava, C. pseudocyperus, C. riparia, C. leporina is a very good source of linoleic acid. The second group, including the remaining species, is a good source of α-linolenic acid. The highest oleic acid contents were observed in C. vulpina. The studied material has shown a low concentration of saturated fatty acids, among which palmitic acid was the main one.Results of the analyses allow for the inclusion of the studied species among plants whose fruits are characterized by a high content of unsaturated fatty acids.Los ácidos grasos de frutos de 13 especies de juncos (Carex L., Cyperaceae fueron analizados. El contenido de aceite en los frutos de juncos estudiados vario desde un 3.73 a un 46.52%. En los aceites de los frutos estudiados fueron identificados 14 ácidos grasos diferentes. Los principales ácidos grasos insaturados fueron los ácidos linoleico, α-linolenico, oleico, n-7 palmitoleico, n-9 palmitoleico, octadecenoico y eicosanoico. Los siguientes ácidos grasos fueron encontrados en mayor cantidad: ácido linoleico, ácido oleico, ácido α-linolenico, y ácido palmítico. Basado en la composición de ácidos grasos, las especies estudiadas pueden ser divididas en dos grupos. El primer grupo (C. flava, C. pseudocyperus, C. riparia, C. leporina es una muy buena fuente de ácido linoleico. El segundo grupo, que incluye las especies restantes, es una buena fuente

  1. Illustrations and studies in Neotropical Orchidaceae. 6. The Lepanthes guatemalensis group (Pleurothallidinae in Costa Rica

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    Pupulin, Franco

    2014-06-01

    Full Text Available We revise and characterize the group of species close to Lepanthes guatemalensis. The group comprises eight species in Costa Rica. Three new species are described and illustrated. Lepanthes durikäensis is distinguished by the non resupinate flowers, the lateral sepals ovate with the apical tails diverging, the lower lobe of petals lanceolate-subfalcate, up-curved and the pinkish column. Lepanthes leporina is recognized by the resupinate flowers with yellow sepals, faintly suffused with red, the petals violet, the lip orange, the bifid synsepal with the apices of the lateral sepals not forming tails, the lateral sepals subequal to the dorsal sepal, the petals markedly convex with the upper lobe elliptic-lanceolate and the lobes of the lip connivent at apex. Lepanthes sanctiorum is characterized by the small plants less than 1.1 cm tall, the short peduncle less than 10 mm long, the petals as wide as the lip length and the blades of the lip distinctly diverging at apex. All the species are described and illustrated on the basis of Costa Rican material. A key to the species of the group is provided.Revisamos y caracterizamos el grupo de especies cercanas a Lepanthes guatemalensis. El grupo está compuesto por ocho especies en Costa Rica. Se describen e ilustran tres especies nuevas. Lepanthes durikäensis se caracteriza por las flores no resupinadas, los sépalos laterales ovados, con las colas apicales divergentes, el lóbulo inferior de los pétalos lanceolado-subfalcado, con curvatura hacia arriba y la columna rosada. Lepanthes leporina es reconocida por las flores resupinadas, los sépalos amarillos y ligeramente teñidos de rojo, los pétalos violeta, el labelo naranja, el sinsépalo bífido con los ápices de los sépalos laterales que no forman colas, los sépalos laterales subiguales al sépalo dorsal, los pétalos marcadamente convexo con el lóbulo superior elíptico-lanceolado y los lóbulos del labelo conniventes en el ápice. Lepanthes

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

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    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.

  3. Molecular Epidemiology Investigation of Obesity and Lethal Prostate Cancer

    Science.gov (United States)

    2015-09-01

    unmethylated and active, a cryptic promoter located within the 5ʹ end of IAP’s long terminal repeat hijacks the transcriptional control of the agouti gene...methyl donors.88 Alternatively, peri-conceptional feeding of a methyl- deficient diet to female sheep resulted in adult offspring with CpG islands that...and physical activity for cancer prevention: reducing the risk of cancer with healthy food choices and physical activity. CA Cancer J Clin 2012; 62

  4. Simultaneous Gene Editing by Injection of mRNAs Encoding Transcription Activator-Like Effector Nucleases into Mouse Zygotes

    OpenAIRE

    Li, Chunliang; Qi, Rong; Singleterry, Rebecca; Hyle, Judith; Balch, Amanda; Li, Xiuling; Sublett, Jack; Berns, Hartmut; Valentine, Marcus; Valentine, Virginia; Sherr, Charles J.

    2014-01-01

    Injection of transcription activator-like effector nucleases (TALEN) mRNAs into mouse zygotes transferred into foster mothers efficiently generated founder mice with heritable mutations in targeted genes. Immunofluorescence visualization of phosphorylated histone 2A (γH2AX) combined with fluorescence in situ hybridization revealed that TALEN pairs targeting the Agouti locus induced site-directed DNA breaks in zygotes within 6 h of injection, an activity that continued at reduced efficiency in...

  5. The central melanocortin system affects the hypothalamo-pituitary thyroid axis and may mediate the effect of leptin

    OpenAIRE

    2000-01-01

    Prolonged fasting is associated with a downregulation of the hypothalamo-pituitary thyroid (H-P-T) axis, which is reversed by administration of leptin. The hypothalamic melanocortin system regulates energy balance and mediates a number of central effects of leptin. In this study, we show that hypothalamic melanocortins can stimulate the thyroid axis and that their antagonist, agouti-related peptide (Agrp), can inhibit it. Intracerebroventricular (ICV) administration of Agrp (83-132) decreased...

  6. The orally active melanocortin-4 receptor antagonist BL-6020/979: a promising candidate for the treatment of cancer cachexia

    OpenAIRE

    Dallmann, R; Weyermann, P.; Anklin, C; Boroff, M.; Bray-French, K.; Cardel, B; Courdier-Fruh, I; Deppe, H.; Dubach-Powell, J.; Erb, M.; Haefeli, R H; Henneböhle, M; Herzner, H.; Marks, D. L.; Hufschmid, M

    2011-01-01

    BACKGROUND: Under physiological conditions, the melanocortin system is a crucial part of the complex network regulating food intake and energy expenditure. In pathological states, like cachexia, these two parameters are deregulated, i.e., food intake is decreased and energy expenditure is increased-a vicious combination leading to catabolism. Agouti-related protein (AgRP), the endogenous antagonist at the melanocortin-4 receptor (MC-4R), was found to increase food intake and to reduce energy ...

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

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    Heleen Rienstra

    Full Text Available BACKGROUND: 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. METHODS: 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. FINDINGS: 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 (p<0.01 compared to isografts and non-transplanted controls, which was associated with induced perlecan expression underneath the lymphatic endothelium (p<0.05 and p<0.01 compared to isografts and non-transplanted controls, respectively. Both the magnitude of lymphangiogenesis and perlecan expression correlated with severity of interstitial fibrosis and impaired graft function

  8. Fatty acids composition of fruits of selected Central European sedges (Carex L. Cyperaceae)

    Energy Technology Data Exchange (ETDEWEB)

    Bogucka-Kocka, A.; Janyszek, M.

    2010-07-01

    Fatty acids in the fruits of 13 sedge species (Ca rex L., Cyperaceae) were analyzed. The oil contents in the fruits of the studied sedges ranged from 3.73 and 46.52%. In the studied fruit oils 14 different fatty acids were identified. The main unsaturated fatty acids were: linoleic, a-linolenic, oleic, oleo palmitic n-7; oleo palmitic n-9, octadecenic, and eicosenoic acids. The following acids were found in the greatest quantities: linoleic, oleic, a-linolenic and palmitic acids. Based on the fatty acid composition, studied taxa can be divided in two groups. The first group (C. flava, C. pseudocyperus, C. riparia, C. leporina) is a very good source of linoleic acid. The second group, including the remaining species, is a good source of a-linolenic acid. The highest oleic acid contents were observed in C. vulpina. The studied material has shown a low concentration of saturated fatty acids, among which palmitic acid was the main one.Results of the analyses allow for the inclusion of the studied species among plants whose fruits are characterized by a high content of unsaturated fatty acids. (Author)

  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. 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

  11. Comprehensive Assessment of Oxidatively Induced Modifications of DNA in a Rat Model of Human Wilson's Disease.

    Science.gov (United States)

    Yu, Yang; Guerrero, Candace R; Liu, Shuo; Amato, Nicholas J; Sharma, Yogeshwar; Gupta, Sanjeev; Wang, Yinsheng

    2016-03-01

    Defective copper excretion from hepatocytes in Wilson's disease causes accumulation of copper ions with increased generation of reactive oxygen species via the Fenton-type reaction. Here we developed a nanoflow liquid chromatography-nanoelectrospray ionization-tandem mass spectrometry coupled with the isotope-dilution method for the simultaneous quantification of oxidatively induced DNA modifications. This method enabled measurement, in microgram quantities of DNA, of four oxidative stress-induced lesions, including direct ROS-induced purine cyclonucleosides (cPus) and two exocyclic adducts induced by byproducts of lipid peroxidation, i.e. 1,N(6)-etheno-2'-deoxyadenosine (εdA) and 1,N(2)-etheno-2'-deoxyguanosine (εdG). Analysis of liver tissues of Long-Evans Cinnamon rats, which constitute an animal model of human Wilson's disease, and their healthy counterparts [i.e. Long-Evans Agouti rats] showed significantly higher levels of all four DNA lesions in Long-Evans Cinnamon than Long-Evans Agouti rats. Moreover, cPus were present at much higher levels than εdA and εdG lesions. In contrast, the level of 5-hydroxymethyl-2'-deoxycytidine (5-HmdC), an oxidation product of 5-methyl-2'-deoxycytidine (5-mdC), was markedly lower in the liver tissues of Long-Evans Cinnamon than Long-Evans Agouti rats, though no differences were observed for the levels of 5-mdC. In vitro biochemical assay showed that Cu(2+) ions could directly inhibit the activity of Tet enzymes. Together, these results suggest that aberrant copper accumulation may perturb genomic stability by elevating oxidatively induced DNA lesions, and by altering epigenetic pathways of gene regulation.

  12. Anorexia in rats caused by a valine-deficient diet is not ameliorated by systemic ghrelin treatment.

    Science.gov (United States)

    Goto, S; Nagao, K; Bannai, M; Takahashi, M; Nakahara, K; Kangawa, K; Murakami, N

    2010-03-10

    Rodents exhibit aversive behavior toward a diet that lacks at least one of the essential amino acids. We sought to determine whether the particular form of anorexia caused by such diets could be ameliorated by the administration of orexigenic peptides while simultaneously analyzing the neural mechanisms underlying anorexia. Rats were fed a valine-deficient diet, which induced severe anorexia (reducing food consumption by 80%). The severe anorexia was associated with a significant decrease in the cerebrospinal fluid valine concentration and hyper-ghrelinemia. Between 6 and 12 days after initiation of the valine-deficient diet, we injected rats twice daily with valine and/or an orexigenic peptide (ghrelin, neuropeptide Y, or agouti-related protein) either i.p. or i.c.v.. We then measured dietary intake. An i.c.v. valine injection allowed earlier food intake compared with an i.p valine injection and increased the density of c-Fos-positive ependymal cells lining the third ventricle. Whereas an i.c.v. injection of ghrelin or neuropeptide Y increased consumption of the valine-deficient diet, i.p injection of ghrelin or i.c.v. injection of agouti-related protein did not. Following i.c.v. administration of either valine or ghrelin, we did not observe complete recovery of consumption of the valine-deficient diet. This may be due to the ineffectiveness of peripheral ghrelin and central agouti-related protein and/or to conditioned aversion to the valine-deficient diet. Since ghrelin is known to be involved in food anticipatory activities, whether the hyper-ghrelinemia observed in valine-deficient rats play role in foraging behavior other than food intake is the future study to be investigated.

  13. 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.

  14. Revisión sobre la herencia del color de la capa en ganado bovino

    OpenAIRE

    Royo, L. J.; Fernández, Itziar; Álvarez, Isabel; Rodríguez, A.; Goyache, Félix

    2013-01-01

    Coat colour affects differentiation of populations into breeds. Additionally some authors proposed the use of the genes responsible of coat colour variation in diversity studies. In this work we review the knowledge on genes affecting coat colour (loci Extension or Mc r1 and Agouti or ASIP) AND SPOTTING PATTERNS (KIT and MGF) El interés por el color de la capa en ganado bovino reside en su importancia para la formación y diferenciación de las razas y en la posible utilización de los genes ...

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

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    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

  16. Spontaneous hepatic copper accumulation in Long-Evans Cinnamon rats with hereditary hepatitis. A model of Wilson's disease.

    OpenAIRE

    Li, Y; Togashi, Y; S. Sato; Emoto, T; J. H. Kang; TAKEICHI N.; Kobayashi, H; Y. Kojima; Une, Y.; Uchino, J

    1991-01-01

    Long-Evans Cinnamon (LEC) rats, an inbred strain of a mutant rat isolated from Long-Evans rats, develop hereditary hepatitis. To elucidate the role of copper metabolism in the development of the hepatitis in LEC rats, we examined the copper concentration in the tissues and serum levels of copper and ceruloplasmin. Copper concentration in the liver of LEC rats was over 40 times that of normal Long-Evans Agouti (LEA) rats, while the serum ceruloplasmin and copper concentrations in LEC rats decr...

  17. Progress in the Study on MC4R Gene%MC4R基因研究进展

    Institute of Scientific and Technical Information of China (English)

    左北瑶; 钱宏光

    2011-01-01

    MC4R was a class of peptide secreted by the hypothalamic ventromedial nucleus,and one of 5 subtypes of the melanocortin receptor family(MC1 -5R). In mammals,MC4R could mediate the leptin,and it was an important signaling molecule that might regulate the balance of energy and energy-homeostasis,and combined with melanocortin or agouti protein and agouti related protein,it played a key role in controlling the appetite and body weight steady-state.Thus,MC4R was given much attention as an important regulator in human obesity research.Recent studies have shown that back fat thickness of the sheep are associated with G→A mutation in 1 232 point of MC4R, and AG type and AA type have higher back fat thickness than GG type.%黑素皮质素受体-4( melanocortin-4 receptor,MC4R)是下丘脑腹内侧核分泌的一类肽类物质,为黑素皮质素受体家族5个亚型(MC1-5R)之一.在哺乳动物中,MC4R具有介导瘦蛋白(leptin)的功能,是一个调节能量平衡与能量动态平衡的重要信号分子,可与其内源性配体黑素皮质素激素(melanocortin,MC)或刺鼠色蛋白(agouti protein,agouti蛋白)和agouti相关蛋白(agouti related protein,AGRP)相结合,从而在控制食欲和体重稳态中起关键作用.因此,MC4R在人类肥胖研究中作为重要的调节因子倍受关注.最近有研究表明:MC4R的1232位点的G→A的突变与绵羊背膘厚度间存在关联,AG和AA型较GG型具有较高的背膘厚度.

  18. A monograph of Otidea (Pyronemataceae, Pezizomycetes).

    Science.gov (United States)

    Olariaga, I; Van Vooren, N; Carbone, M; Hansen, K

    2015-12-01

    The easily recognised genus Otidea is subjected to numerous problems in species identification. A number of old names have undergone various interpretations, materials from different continents have not been compared and misidentifications occur commonly. In this context, Otidea is monographed, based on our multiple gene phylogenies assessing species boundaries and comparative morphological characters (see Hansen & Olariaga 2015). All names combined in or synonymised with Otidea are dealt with. Thirty-three species are treated, with full descriptions and colour illustrations provided for 25 of these. Five new species are described, viz. O. borealis, O. brunneoparva, O. oregonensis, O. pseudoleporina and O. subformicarum. Otidea cantharella var. minor and O. onotica var. brevispora are elevated to species rank. Otideopsis kaushalii is combined in the genus Otidea. A key to the species of Otidea is given. An LSU dataset containing 167 sequences (with 44 newly generated in this study) is analysed to place collections and determine whether the named Otidea sequences in GenBank were identified correctly. Fourty-nine new ITS sequences were generated in this study. The ITS region is too variable to align across Otidea, but had low intraspecific variation and it aided in species identifications. Thirty type collections were studied, and ITS and LSU sequences are provided for 12 of these. A neotype is designated for O. cantharella and epitypes for O. concinna, O. leporina and O. onotica, along with several lectotypifications. The apothecial colour and shape, and spore characters are important for species identification. We conclude that to distinguish closely related or morphologically similar species, a combination of additional features are needed, i.e. the shape of the paraphyses, ectal excipulum structure, types of ectal excipulum resinous exudates and their reactions in Melzer's reagent and KOH, tomentum and basal mycelium colours and exudates. The KOH reaction of

  19. [Wildlife damage mitigation in agricultural crops in a Bolivian montane forest].

    Science.gov (United States)

    Perez, Eddy; Pacheco, Luis F

    2014-12-01

    Wildlife is often blamed for causing damage to human activities, including agricultural practices and the result may be a conflict between human interests and species conservation. A formal assessment of the magnitude of damage is necessary to adequately conduct management practices and an assessment of the efficiency of different management practices is necessary to enable managers to mitigate the conflict with rural people. This study was carried out to evaluate the effectiveness of agricultural management practices and controlled hunting in reducing damage to subsistence annual crops at the Cotapata National Park and Natural Area of Integrated Management. The design included seven fields with modified agricultural practices, four fields subjected to control hunting, and five fields held as controls. We registered cultivar type, density, frequency of visiting species to the field, crops lost to wildlife, species responsible for damage, and crop biomass. Most frequent species in the fields were Dasyprocta punctata and Dasypus novemcinctus. Hunted plots were visited 1.6 times more frequently than agriculturally managed plots. Crop lost to wildlife averaged 7.28% at agriculturally managed plots, 4.59% in plots subjected to hunting, and 27.61% in control plots. Species mainly responsible for damage were Pecari tajacu, D. punctata, and Sapajus apella. We concluded that both management strategies were effective to reduce damage by >50% as compared to unmanaged crop plots.

  20. Natural regeneration and dispersion of seeds of the imbuzeiro (spondias tuberosa Arruda in the Pernambuco hinterland, Brazil

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    Luiza Teixeira de Lima Brito

    2009-08-01

    Full Text Available This work had as objective to evaluate the dispersion of the seeds of imbuzeiro (Spondias tuberosa Arruda for the animals and the survival of plants in caatinga. The work was carried out in the period from October of 2002 to December of 2005 in degraded and native area of caatinga. They had been selected to perhaps, 16 plants of imbuzeiro, being eight plants in each area. In each plant twelve transectos of 1 m of width for 25 m had been demarcated, where the seeds found in the young ground and plants. The used experimental delineation was block-type to perhaps in factorial project 5 x 2, with four repetitions. 1003.5 seeds.m-2 had been, on average, in the first units you show of caatinga native and in caatinga degraded, it was observed, on average, 31.25 seeds m-2. In the native area of caatinga they had been registered 2.5 plants m-2, on average, in the first units you show during the rainy station. The dispersive ones of the seeds observed in the native area of catinga had been the deer-catingueiro (Mazama gouazoubira, the cotia (Dasyprocta cf. prymnolopha, caititu (Tayassu tajacu, the fox (Dusicyon thous, the teiú (Tupinambis merianae, the tatu-peba (Euphractus sexcinctus of the guará (Procyon cancrivous the area of caatinga e na área de caatinga degraded the sheep (Capra hircus.Key-words: rain, tree, seedlings, emergency, germination.

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

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    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..........

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

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    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.

  3. 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.

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

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    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.From 1982 to 1986, investigations on the natural infection with leishmanias of the sylvatic and commensal mammals were carried out around the city of Jacobina, Bahia, one of the oldest endemic foci of visceral leishmaniasis in Brazil. The species of Marsupialia Didelphis albiventris predominated, with the rate of 44%, over the total of 213 specimens belonging to only 11 different species of mammals collected there. Among the 84 specimens of D. albiventris examined, 2(2.3% were infected with Leishmania donovani sensu lato; 1 with L. mexicana amazonensis, 1 with L. braziliensis sub species, and 3 with Trypanosoma cruzi. Also, amastigote suspected bodies were

  5. 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

  6. 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

  7. 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.

  8. mTORC1 signaling in Agrp neurons mediates circadian expression of Agrp and NPY but is dispensable for regulation of feeding behavior.

    Science.gov (United States)

    Albert, Verena; Cornu, Marion; Hall, Michael N

    2015-08-21

    Orexigenic agouti-related protein/neuropeptide Y (Agrp/NPY) neurons and an orexigenic pro-opiomelanocortin (POMC) neurons of the hypothalamus regulate feeding behavior and energy homeostasis. An understanding of the molecular signaling pathways that regulate Agrp/NPY and POMC function could lead to novel treatments for metabolic disorders. Target of Rapamycin Complex 1 (TORC1) is a nutrient-activated protein kinase and central controller of growth and metabolism. We therefore investigated the role of mammalian TORC1 (mTORC1) in Agrp neurons. We generated and characterized Agrp neuron-specific raptor knockout (Agrp-raptor KO) mice. Agrp-raptor KO mice displayed reduced, non-circadian expression of Agrp and NPY but normal feeding behavior and energy homeostasis on both normal and high fat diet. Thus, mTORC1 in Agrp neurons controls circadian expression of orexigenic neuropeptides but is dispensable for the regulation of feeding behavior and energy metabolism.

  9. Peromyscus as a Mammalian Epigenetic Model

    Directory of Open Access Journals (Sweden)

    Kimberly R. Shorter

    2012-01-01

    Full Text Available Deer mice (Peromyscus offer an opportunity for studying the effects of natural genetic/epigenetic variation with several advantages over other mammalian models. These advantages include the ability to study natural genetic variation and behaviors not present in other models. Moreover, their life histories in diverse habitats are well studied. Peromyscus resources include genome sequencing in progress, a nascent genetic map, and >90,000 ESTs. Here we review epigenetic studies and relevant areas of research involving Peromyscus models. These include differences in epigenetic control between species and substance effects on behavior. We also present new data on the epigenetic effects of diet on coat-color using a Peromyscus model of agouti overexpression. We suggest that in terms of tying natural genetic variants with environmental effects in producing specific epigenetic effects, Peromyscus models have a great potential.

  10. 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

    2014-07-01

    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.

  11. Physical Activity and Obesity Related Hormones

    Directory of Open Access Journals (Sweden)

    Mehdi Hedayati

    2014-08-01

    Full Text Available Probably, obesity can be considered as the most common metabolic disorder. In other words, the control of metabolism is disrupted in this condition. The most important metabolic control is performed by hormones. Today, adipose tissue is considered as an active tissue in secretion of hormones. In obesity, in addition to adipose tissue hormones, effective neuropeptides on appetite are interfered. There are 4 main approaches in the management and treatment of obesity including nutrition and diet therapy, physical activity, medical and surgical approaches. The specialists and obese patients prefer the first and second approaches. Physical activity helps to control and treat this disorder by influencing on obesity-related hormones. The main obesity-related hormones are ghrelin, agouti, obestatin, leptin, adiponectin, nesfatin, visfatin, tumor necrosis factor, interleukin-6, and resistin. In this review, the effect of physical activity on 10 major obesity-related hormones has been discussed.

  12. Synthesis and structure-active relationship of 1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline anticonvulsants.

    Science.gov (United States)

    Gitto, Rosaria; De Luca, Laura; Ferro, Stefania; Agnello, Stefano; Russo, Emilio; De Sarro, Giovanbattista; Chimirri, Alba

    2010-12-01

    We have previously disclosed that some 6,7-dimethoxyisoquinoline derivatives are able to produce anticonvulsant effects in different animal models of epilepsy. Following these studies this paper describes the synthesis of a small series of new 1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines strictly related to previously reported analogues. This novel series of isoquinolines was designed on the basis of well defined structure-active relationship (SAR) information already acquired for this class of anticonvulsant agents. The pharmacological effects of the new synthesized compounds were evaluated against audiogenic seizures in Dilute Brown non-Agouti (DBA/2) mice. The preliminary pharmacological screening led to the identification of a new active molecule the 2-acetyl-1-(4'-methylphenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (6d) that displayed significant anticonvulsant activity. Computational studies helped to rationalize these obtained pharmacological results.

  13. 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.

  14. Lack of genetic association among coat colors, progressive retinal atrophy and polycystic kidney disease in Persian cats.

    Science.gov (United States)

    Rah, HyungChul; Maggs, David J; Lyons, Leslie A

    2006-10-01

    An inherited form of progressive retinal atrophy (PRA) is recognized in Persian cats; however, the prevalence of PRA in the breed has not been determined. Breeders suggest that cats from only brown ('chocolate') or Himalayan ('pointed') lines are at risk for PRA, suggesting the disease is not widespread. This study was designed to evaluate whether PRA in Persian cats is associated with three coat colors, including chocolate, or with a highly prevalent inherited disease in this breed--polycystic kidney disease (PKD). Sixty related cats were evaluated for PRA by ophthalmic examination and genetically typed for PKD and the mutations that cause coat color variants in agouti, brown and color (producing the pointed coloration in Himalayan). No associations were identified among any of the traits, including between PRA and chocolate. These data suggest that PRA is not limited to cats with chocolate coat coloration and breeders and veterinarians should be aware that the prevalence of the disease may be higher than currently claimed.

  15. Mammalian comparative sequence analysis of the Agrp locus.

    Directory of Open Access Journals (Sweden)

    Christopher B Kaelin

    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.

  16. 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.’

  17. 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.

  18. Inheritance of goat coat colors.

    Science.gov (United States)

    Adalsteinsson, S; Sponenberg, D P; Alexieva, S; Russel, A J

    1994-01-01

    Goat color inheritance was evaluated based on color description of 218 kids and their parents (10 sires, 178 dams) from mixed crosses between several goat populations in an experiment on cashmere fiber production. Altogether 10 color patterns were observed. They were postulated to be caused by 10 alleles at the Agouti locus, with the allele for white or tan color being the top dominant allele, and the nine others codominant. The bottom recessive allele, for nonagouti color, was the 11th allele at this locus. The postulated alleles are white or tan (A(wt)), black mask (A(blm)), bezoar (A(bz)), badgerface (A(b)), grey (A(g)), lightbelly (A(lb)), swiss markings (A(sm)), lateral stripes (A(ls)), mahogany (A(mh)), red cheek (A(rc)), and nonagouti (Aa). Two types of eumelanin pigment were observed, black and light brown, the latter being dominant. Recessive brown was not observed.

  19. 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.

  20. 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 

  1. Cannabinoid treatment renders neurons less vulnerable than oligodendrocytes in experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Hasseldam, Henrik; Johansen, Flemming Fryd

    2011-01-01

    ABSTRACT Using the rat model Experimental Autoimmune Encephalomyelitis (EAE), we have investigated the cytokinetical and cellular events of axonal degeneration and demyelination following treatment with 5 mg/kg/24h R(+)WIN55,212-2 or 10 mg/kg/24h R(+)WIN55,212-2, which have immunosuppressive...... effects. EAE was induced using MOG(1-125) in Dark Agouti rats and treatment was initiated at symptom debut and continued until first relapse culminated. The central nervous system (CNS) cell death including caspase and calpain activation, axonal degeneration and demyelination as well as a wide range...... of immunological parameters were quantified. We found a significant reduction in axonal degeneration associated with reduced calpain 1 following treatment with 5 mg/kg/24h R(+)WIN55,212-2. Treatment with 10 mg/kg/24h resulted furthermore in an improved clinical performance and a reduction in inflammatory activity...

  2. 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

  3. Cortical grey matter demyelination can be induced by elevated pro-inflammatory cytokines in the subarachnoid space of MOG-immunized rats.

    Science.gov (United States)

    Gardner, Christopher; Magliozzi, Roberta; Durrenberger, Pascal F; Howell, Owain W; Rundle, Jon; Reynolds, Richard

    2013-12-01

    A substantial proportion of cases with secondary progressive multiple sclerosis have extensive inflammation in the leptomeninges that is associated with increased subpial demyelination, neuronal loss and an exacerbated disease course. However, the mechanisms underlying this extensive subpial pathology are poorly understood. We hypothesize that pro-inflammatory cytokine production within the meninges may be a key to this process. Post-mortem cerebrospinal fluid and dissected cerebral leptomeningeal tissue from patients with multiple sclerosis were used to study the presence of tumour necrosis factor and interferon gamma protein and messenger RNA levels. A novel model of subpial cortical grey matter demyelination was set up in Dark Agouti rats and analysed using quantitative immunohistochemistry. Increased expression of the pro-inflammatory cytokines tumour necrosis factor and interferon gamma was found in the meninges of cases with secondary progressive multiple sclerosis exhibiting tertiary lymphoid-like structures. Injection of tumour necrosis factor and interferon gamma into the subarachnoid space of female Dark Agouti rats pre-immunized with a subclinical dose of myelin oligodendrocyte glycoprotein mimicked the pathology seen in multiple sclerosis, including infiltration of lymphocytes (CD4+ and CD8+ T cells and CD79+ B cells) into the meninges and extensive subpial demyelination. Extensive microglial/macrophage activation was present in a gradient from the pial surface to deeper cortical layers. Demyelination did not occur in control animals immunized with incomplete Freund's adjuvant and injected with cytokines. These results support the hypothesis that pro-inflammatory molecules produced in the meninges play a major role in cortical demyelination in multiple sclerosis, but also emphasize the involvement of an anti-myelin immune response.

  4. 绵羊黑色素合成相关基因的研究进展%Research Progress of Genes Related to Melanin Synthesis in Sheep

    Institute of Scientific and Technical Information of China (English)

    孟浩浩; 许瑞霞; 代蓉; 李辉; 李良远; 万鹏程; 石国庆

    2014-01-01

    毛色是一种可利用的遗传标记。在确定杂交组合、品种纯度和亲缘关系以及评价产品质量等方面均有一定的用途。哺乳动物毛色是由黑色素细胞产生的真黑素和褐黑素二者的分布和比例决定的。控制哺乳动物毛色色素的基因有很多,着重对黑色素合成相关基因酪氨酸酶基因(TYR)、黑素皮质激素受体1基因(MC1R)、鼠灰信号蛋白基因(Agouti)、酪氨酸酶相关蛋白1基因(TYRP1)的生物学功能及其遗传变异机制进行了综述。%As a genetic marker,coat color plays an important roles in determining cross combination,breed purity and phylogenesis. Coat color of mammals is determined by the distribution and proportion of eumelanin and pheomelanin,which produced by melanocytes. This article summarized the biological functions and the genetic variation of Tyrosinase gene(Tyr),Melanocortin 1 receptor gene(MC1R),Agouti signaling protein gene(Agouti)and Tyrosinase-related protein gene(TYRP1).

  5. Hypothalamic neuropeptide gene expression during recovery from food restriction superimposed on short-day photoperiod-induced weight loss in the Siberian hamster.

    Science.gov (United States)

    Archer, Zoë A; Moar, Kim M; Logie, Tracy J; Reilly, Laura; Stevens, Valerie; Morgan, Peter J; Mercer, Julian G

    2007-09-01

    Previously, 40% food restriction of male Siberian hamsters over 21 days in short-day (SD) photoperiod induced characteristic changes in expression of hypothalamic arcuate nucleus energy balance genes; mRNAs for neuropeptide Y, agouti-related peptide, and leptin receptor were upregulated, and those of proopiomelanocortin and cocaine- and amphetamine-regulated transcript were depressed. The present study examined the effect of refeeding hamsters for 6 days (approximately 50% recovery of weight differential) or 19 days (resumption of appropriate weight trajectory). Hyperphagia continued throughout refeeding, but differences in fat pad weights and leptin levels had disappeared after 19 days. Cocaine- and amphetamine-regulated transcript gene expression was depressed by prior restriction in both refed groups. The depressive effect of prior restriction on proopiomelanocortin gene expression had disappeared after 19 days of refeeding. There was no effect of prior food restriction on neuropeptide Y or agouti-related peptide gene expression. Expression of the anorexigenic brain-derived neurotrophic factor was downregulated in the ventromedial nucleus after SD exposure for 12 wk. In the SD food restriction study, there were effects of photoperiod on brain-derived neurotrophic factor gene expression but not of prior food restriction. Hypothalamic energy balance genes in the hamster respond asynchronously to return to a seasonally appropriate body weight. The achievement of this weight rather than the weight at which caloric restriction was imposed is the critical factor. The differential responses of hypothalamic energy balance genes to food restriction and refeeding are poorly characterized in any species, a critical issue given their potential relevance to human weight loss strategies that involve caloric restriction.

  6. Complex regulation of mammalian target of rapamycin complex 1 in the basomedial hypothalamus by leptin and nutritional status.

    Science.gov (United States)

    Villanueva, Eneida C; Münzberg, Heike; Cota, Daniela; Leshan, Rebecca L; Kopp, Keely; Ishida-Takahashi, Ryoko; Jones, Justin C; Fingar, Diane C; Seeley, Randy J; Myers, Martin G

    2009-10-01

    The medial basal hypothalamus, including the arcuate nucleus (ARC) and the ventromedial hypothalamic nucleus (VMH), integrates signals of energy status to modulate metabolism and energy balance. Leptin and feeding regulate the mammalian target of rapamycin complex 1 (mTORC1) in the hypothalamus, and hypothalamic mTORC1 contributes to the control of feeding and energy balance. To determine the mechanisms by which leptin modulates mTORC1 in specific hypothalamic neurons, we immunohistochemically assessed the mTORC1-dependent phosphorylation of ribosomal protein S6 (pS6). In addition to confirming the modulation of ARC mTORC1 activity by acute leptin treatment, this analysis revealed the robust activation of mTORC1-dependent ARC pS6 in response to fasting and leptin deficiency in leptin receptor-expressing Agouti-related protein neurons. In contrast, fasting and leptin deficiency suppress VMH mTORC1 signaling. The appropriate regulation of ARC mTORC1 by mutant leptin receptor isoforms correlated with their ability to suppress the activity of Agouti-related protein neurons, suggesting the potential stimulation of mTORC1 by the neuronal activity. Indeed, fasting- and leptin deficiency-induced pS6-immunoreactivity (IR) extensively colocalized with c-Fos-IR in ARC and VMH neurons. Furthermore, ghrelin, which activates orexigenic ARC neurons, increased ARC mTORC1 activity and induced colocalized pS6- and c-Fos-IR. Thus, neuronal activity promotes mTORC1/pS6 in response to signals of energy deficit. In contrast, insulin, which activates mTORC1 via the phosphatidylinositol 3-kinase pathway, increased ARC and VMH pS6-IR in the absence of neuronal activation. The regulation of mTORC1 in the basomedial hypothalamus thus varies by cell and stimulus type, as opposed to responding in a uniform manner to nutritional and hormonal perturbations.

  7. Taxonomic revision and cladistic analysis of Avicularia Lamarck, 1818 (Araneae, Theraphosidae, Aviculariinae) with description of three new aviculariine genera

    Science.gov (United States)

    Fukushima, Caroline Sayuri; Bertani, Rogério

    2017-01-01

    to accommodate former Avicularia species: Caribena gen. n., composed of Caribena laeta (C. L. Koch, 1842), comb. n. and Caribena versicolor (Walckenaer, 1837), comb. n.; Antillena gen. n., with a single species, Antillena rickwesti (Bertani & Huff, 2013), comb. n., both from the Caribbean; and Ybyrapora gen. n., composed of Ybyrapora sooretama (Bertani & Fukushima, 2009), comb. n., Ybyrapora gamba (Bertani & Fukushima, 2009), comb. n. and Ybyrapora diversipes (C. L. Koch, 1842), comb. n. from Brazilian rainforest. The subspecies Avicularia avicularia variegata F. O. Pickard-Cambridge, 1896 is elevated to species status, resulting in the combination Avicularia variegata (F. O. Pickard-Cambridge, 1896) stat. n.. The following new synonymies are established: Avicularia velutina Simon 1889, Avicularia exilis Strand, 1907, Avicularia ancylochyra Mello-Leitão, 1923, Avicularia cuminami Mello-Leitão, 1930, and Avicularia nigrotaeniata Mello-Leitão, 1940 are junior synonyms of Avicularia avicularia; Avicularia bicegoi Mello-Leitão, 1923 is a junior synonym of Avicularia variegata stat. n., and Avicularia urticans Schmidt, 1994 is a junior synonym of Avicularia juruensis Mello-Leitão, 1923. Species transferred to other genera: Avicularia affinis (Nicolet, 1849) is transferred to Euathlus Ausserer, 1875, making the new combination Euathlus affinis (Nicolet, 1849), comb. n.; Avicularia subvulpina Strand, 1906 is transferred to Grammostola Simon, 1892, making the new combination Grammostola subvulpina (Strand, 1906), comb. n.; Avicularia aymara (Chamberlin, 1916) is transferred to Thrixopelma Schmidt, 1994, making the new combination Thrixopelma aymara (Chamberlin, 1916), comb. n.; Avicularia leporina (C. L. Koch, 1841) and Avicularia plantaris (C. L. Koch, 1842) are transferred to Iridopelma Pocock, 1901, making the new combinations Iridopelma leporina (C. L. Koch, 1841), comb. n. and Iridopelma plantaris (C. L. Koch, 1842), comb. n.; the two last species are considered

  8. Taxonomic revision and cladistic analysis of Avicularia Lamarck, 1818 (Araneae, Theraphosidae, Aviculariinae) with description of three new aviculariine genera.

    Science.gov (United States)

    Fukushima, Caroline Sayuri; Bertani, Rogério

    2017-01-01

    former Avicularia species: Caribenagen. n., composed of Caribena laeta (C. L. Koch, 1842), comb. n. and Caribena versicolor (Walckenaer, 1837), comb. n.; Antillenagen. n., with a single species, Antillena rickwesti (Bertani & Huff, 2013), comb. n., both from the Caribbean; and Ybyraporagen. n., composed of Ybyrapora sooretama (Bertani & Fukushima, 2009), comb. n., Ybyrapora gamba (Bertani & Fukushima, 2009), comb. n. and Ybyrapora diversipes (C. L. Koch, 1842), comb. n. from Brazilian rainforest. The subspecies Avicularia avicularia variegata F. O. Pickard-Cambridge, 1896 is elevated to species status, resulting in the combination Avicularia variegata (F. O. Pickard-Cambridge, 1896) stat. n.. The following new synonymies are established: Avicularia velutina Simon 1889, Avicularia exilis Strand, 1907, Avicularia ancylochyra Mello-Leitão, 1923, Avicularia cuminami Mello-Leitão, 1930, and Avicularia nigrotaeniata Mello-Leitão, 1940 are junior synonyms of Avicularia avicularia; Avicularia bicegoi Mello-Leitão, 1923 is a junior synonym of Avicularia variegatastat. n., and Avicularia urticans Schmidt, 1994 is a junior synonym of Avicularia juruensis Mello-Leitão, 1923. Species transferred to other genera: Avicularia affinis (Nicolet, 1849) is transferred to Euathlus Ausserer, 1875, making the new combination Euathlus affinis (Nicolet, 1849), comb. n.; Avicularia subvulpina Strand, 1906 is transferred to Grammostola Simon, 1892, making the new combination Grammostola subvulpina (Strand, 1906), comb. n.; Avicularia aymara (Chamberlin, 1916) is transferred to Thrixopelma Schmidt, 1994, making the new combination Thrixopelma aymara (Chamberlin, 1916), comb. n.; Avicularia leporina (C. L. Koch, 1841) and Avicularia plantaris (C. L. Koch, 1842) are transferred to Iridopelma Pocock, 1901, making the new combinations Iridopelma leporina (C. L. Koch, 1841), comb. n. and Iridopelma plantaris (C. L. Koch, 1842), comb. n.; the two last species are considered nomina dubia. The

  9. Taxonomic revision and cladistic analysis of Avicularia Lamarck, 1818 (Araneae, Theraphosidae, Aviculariinae with description of three new aviculariine genera01

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    Caroline Sayuri Fukushima

    2017-03-01

    Avicularia species: Caribena gen. n., composed of Caribena laeta (C. L. Koch, 1842, comb. n. and Caribena versicolor (Walckenaer, 1837, comb. n.; Antillena gen. n., with a single species, Antillena rickwesti (Bertani & Huff, 2013, comb. n., both from the Caribbean; and Ybyrapora gen. n., composed of Ybyrapora sooretama (Bertani & Fukushima, 2009, comb. n., Ybyrapora gamba (Bertani & Fukushima, 2009, comb. n. and Ybyrapora diversipes (C. L. Koch, 1842, comb. n. from Brazilian rainforest. The subspecies Avicularia avicularia variegata F. O. Pickard-Cambridge, 1896 is elevated to species status, resulting in the combination Avicularia variegata (F. O. Pickard-Cambridge, 1896 stat. n.. The following new synonymies are established: Avicularia velutina Simon 1889, Avicularia exilis Strand, 1907, Avicularia ancylochyra Mello-Leitão, 1923, Avicularia cuminami Mello-Leitão, 1930, and Avicularia nigrotaeniata Mello-Leitão, 1940 are junior synonyms of A. avicularia; Avicularia bicegoi Mello-Leitão, 1923 is a junior synonym of A. variegata stat. n., and Avicularia urticans Schmidt, 1994 is a junior synonym of Avicularia juruensis Mello-Leitão, 1923. Species transferred to other genera: Avicularia affinis (Nicolet, 1849 is transferred to Euathlus Ausserer, 1875, making the new combination Euathlus affinis (Nicolet, 1849, comb. n.; Avicularia subvulpina Strand, 1906 is transferred to Grammostola Simon, 1892, making the new combination Grammostola subvulpina (Strand, 1906, comb. n.; Avicularia aymara (Chamberlin, 1916 is transferred to Thrixopelma Schmidt, 1994, making the new combination Thrixopelma aymara (Chamberlin, 1916, comb. n.; Avicularia leporina (C. L. Koch, 1841 and Avicularia plantaris (C. L. Koch, 1842 are transferred to Iridopelma Pocock, 1901, making the new combinations Iridopelma leporina (C. L. Koch, 1841, comb. n. and Iridopelma plantaris (C. L. Koch, 1842, comb. n.; the two last species are considered nomina dubia. The following species are considered nomina dubia

  10. [Frugivory and seed dispersal Oenocarpus bataua palm (Arecaceae) in a forest from the Colombian Andes].

    Science.gov (United States)

    Rojas-Robles, Rosario; Stiles, F Gary; Muñoz-Saba, Yaneth

    2012-12-01

    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 Oenocapus bataua palm in fragments of Andean forest, determine the effective dispersers and relate the spatial distribution of palm populations with the dispersion of seeds. To this end, between August 2005-June 2006, observations of the removal of fruits from eight clusters were done, and counting of consumption of fruits beneath 78 palms with mature fruits was undertaken; focal observations of 13 individuals during 90 hours; registration of frugivory with photographic traps during 165 days/nights for a total of 195 photographs and 144 consumption events; experiments with dispersion using 751 perforated fruits/seeds attached to strings and finally, plots to determine spatial distribution all were carried out. In the study area at least five species of mammals ate, dispersed, buried (Sciurus granatensis, Microsciurus mimulus, Dasyprocta punctata y Proechimys sp.), cover (Marmosa robinsoni) and carried the fruits of O. bataua off to caves (Marmosa robinsoni y Proechimys sp.) without damaging the seed. A 21.7% of the fruits were dispersed, 13.2 gnawed or peeled, 5.6% covered, buried and carried to caves. The average distance of removal of seeds and fruits was 3.1m although in a lesser proportion, dispersion events of >50m were recorded. The abundant production of fruits, their size and weight, their intense removal by frugivores, the short dispersion distances, the absence of large size frugivores (reduced by hunting and fragmentation), that might perform long-distance dispersion, and the increase of rodents, especially squirrels, that strongly pressure the fruit resource, generate a spatially restricted seed rain of seeds responsible

  11. @@%Agouti与MITF在不同颜色被毛藏羊皮肤组织中mRNA表达量研究

    Institute of Scientific and Technical Information of China (English)

    韩吉龙; 杨博辉; 岳耀敬; 郭健; 刘建斌; 牛春娥; 郭婷婷; 冯瑞林; 孙晓萍; 吴瑜瑜

    2012-01-01

    @@%为了研究决定藏羊不同颜色被毛形成的分子机制,采用实时荧光定量PCR检测皮肤组织中决定色素形成信号通路中上游调控刺鼠信号蛋白基因(agouti signaling protein (ASIP) gene,Agouti)和下游调控小眼畸形相关转录因子基因(microphthalmia-associated transcription factor,MITF)mRNA的相对表达量,分析同一基因在黑色眼圈、棕黑色颈部和白色体侧被毛皮肤组织的相对表达量差异,对两基因在同一个体同一颜色被毛皮肤组织表达量进行相关性分析.结果表明:Agouti基因在同一个体mRNA表达水平为棕黑色皮肤组织显著性高于黑色和白色(P<0.05),MITF基因mRNA表达量黑色皮肤组织显著性高于棕黑色和白色(P<0.05).通过相关性分析得知,两基因在同一个体同一毛色皮肤组织mRNA相对表达量无显著相关性.推论得知,MITF基因mRNA高表达与藏羊眼圈周围黑色被毛显著相关,Agouti基因mRNA高表达、MITF基因mRNA低表达与其颈部棕黑色被毛可能为其原因,体侧部的白色毛与Agouti和MITF基因mRNA表达无明显相关.

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

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    Patricia Pazos

    2014-01-01

    Full Text Available 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.

  13. Direct modulation of GFAP-expressing glia in the arcuate nucleus bi-directionally regulates feeding

    Science.gov (United States)

    Chen, Naiyan; Barak, Boaz; Sur, Mriganka

    2016-01-01

    Multiple hypothalamic neuronal populations that regulate energy balance have been identified. Although hypothalamic glia exist in abundance and form intimate structural connections with neurons, their roles in energy homeostasis are less known. Here we show that selective Ca2+ activation of glia in the mouse arcuate nucleus (ARC) reversibly induces increased food intake while disruption of Ca2+ signaling pathway in ARC glia reduces food intake. The specific activation of ARC glia enhances the activity of agouti-related protein/neuropeptide Y (AgRP/NPY)-expressing neurons but induces no net response in pro-opiomelanocortin (POMC)-expressing neurons. ARC glial activation non-specifically depolarizes both AgRP/NPY and POMC neurons but a strong inhibitory input to POMC neurons balances the excitation. When AgRP/NPY neurons are inactivated, ARC glial activation fails to evoke any significant changes in food intake. Collectively, these results reveal an important role of ARC glia in the regulation of energy homeostasis through its interaction with distinct neuronal subtype-specific pathways. DOI: http://dx.doi.org/10.7554/eLife.18716.001 PMID:27751234

  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. 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

    2014-04-01

    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.

  16. Pro-inflammatory cytokines play a key role in the development of radiotherapy-induced gastrointestinal mucositis

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    Logan Richard M

    2010-03-01

    Full Text Available Abstract Background Mucositis is a toxic side effect of anti-cancer treatments and is a major focus in cancer research. Pro-inflammatory cytokines have previously been implicated in the pathophysiology of chemotherapy-induced gastrointestinal mucositis. However, whether they play a key role in the development of radiotherapy-induced gastrointestinal mucositis is still unknown. Therefore, the aim of the present study was to characterise the expression of pro-inflammatory cytokines in the gastrointestinal tract using a rat model of fractionated radiotherapy-induced toxicity. Methods Thirty six female Dark Agouti rats were randomly assigned into groups and received 2.5 Gys abdominal radiotherapy three times a week over six weeks. Real time PCR was conducted to determine the relative change in mRNA expression of pro-inflammatory cytokines IL-1β, IL-6 and TNF in the jejunum and colon. Protein expression of IL-1β, IL-6 and TNF in the intestinal epithelium was investigated using qualitative immunohistochemistry. Results Radiotherapy-induced sub-acute damage was associated with significantly upregulated IL-1β, IL-6 and TNF mRNA levels in the jejunum and colon. The majority of pro-inflammatory cytokine protein expression in the jejunum and colon exhibited minimal change following fractionated radiotherapy. Conclusions Pro-inflammatory cytokines play a key role in radiotherapy-induced gastrointestinal mucositis in the sub-acute onset setting.

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

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    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.

  18. Glutamate and GABA as rapid effectors of hypothalamic peptidergic neurons

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    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.

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

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    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.

  20. [The genetic control of mouse coat color and its applications in genetics teaching].

    Science.gov (United States)

    Xing, Wanjin; Morigen, Morigen

    2014-10-01

    Mice are the most commonly used mammalian model. The coat colors of mice are typical Mendelian traits, which have various colors such as white, black, yellow and agouti. The inheritance of mouse coat color is usually stated as an example only in teaching the knowledge of recessive lethal alleles. After searched the related literatures and summarized the molecular mechanisms of mouse coat color inheritance, we further expanded the application of this example into the introduction of the basic concepts of alleles and Mendelian laws, demonstration of the gene structure and function, regulation of gene expression, gene interaction, epigenetic modification, quantitative genetics, as well as evolutionary genetics. By running this example through the whole genetics-teaching lectures, we help the student to form a systemic and developmental view of genetic analysis. At the same time, this teaching approach not only highlights the advancement and integrity of genetics, but also results in a good teaching effect on inspiring the students' interest and attracting students' attention.

  1. Hypothalamic mTOR signaling mediates the orexigenic action of ghrelin.

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    Luís Martins

    Full Text Available Current evidence suggests that ghrelin, a stomach derived peptide, exerts its orexigenic action through specific modulation of Sirtuin1 (SIRT1/p53 and AMP-activated protein kinase (AMPK pathways, which ultimately increase the expression of agouti-related protein (AgRP and neuropeptide Y (NPY in the arcuate nucleus of the hypothalamus (ARC. However, there is a paucity of data about the possible action of ghrelin on alternative metabolic pathways at this level. Here, we demonstrate that ghrelin elicits a marked upregulation of the hypothalamic mammalian target of rapamycin (mTOR signaling pathway. Of note, central inhibition of mTOR signaling with rapamycin decreased ghrelin's orexigenic action and normalized the mRNA expression of AgRP and NPY, as well as their key downstream transcription factors, namely cAMP response-element binding protein (pCREB and forkhead box O1 (FoxO1, total and phosphorylated. Taken together, these data indicate that, in addition to previous reported mechanisms, ghrelin also promotes feeding through modulation of hypothalamic mTOR pathway.

  2. Effects of acute heat stress on gene expression of brain-gut neuropeptides in broiler chickens.

    Science.gov (United States)

    Lei, L; Hepeng, L; Xianlei, L; Hongchao, J; Hai, L; Sheikhahmadi, A; Yufeng, W; Zhigang, S

    2013-11-01

    Heat stress-induced reduction in feed intake is an annoyance of the poultry industry. Feed intake is regulated by complex mechanisms in which brain-gut neuropeptides are involved, but the changes in such neuropeptides in broiler chickens during heat exposure remain unclear. In this study, we investigated the effects of acute heat stress (35°C, 6 h, and 65% relative humidity) on the gene expression of appetite-regulating peptides in the hypothalamus and gastrointestinal tract of broiler chickens at 42 d of age. The hypothalamic mRNA levels of neuropeptide Y, agouti-related peptide, pro-opiomelanocortin, cocaine- and amphetamine-regulated transcript, corticotropin-releasing hormone, melanocortin 4 receptor, melanin-concentrating hormone, prepro-orexin, cholecystokinin (CCK), and ghrelin did not significantly change (P>0.05) in the heat-exposed broiler chickens. However, the mRNA levels of ghrelin in the glandular stomach, duodenum, and jejunum significantly increased and the mRNA level of CCK in the duodenum significantly decreased. The results indicate that acute heat stress had no effect on the gene expression of central appetite-regulating peptides under current experimental conditions; however, some gastrointestinal tract peptides (e.g., ghrelin and CCK) might play a role in the regulation of appetite in acute heat-exposed broiler chickens. Furthermore, ghrelin in the glandular stomach, duodenum, and jejunum might be the main regulative target of acute heat stress induced anorexia.

  3. Genetic regulation of microglia activation, complement expression, and neurodegeneration in a rat model of traumatic brain injury.

    Science.gov (United States)

    Bellander, Bo-Michael; Lidman, Olle; Ohlsson, Marcus; Meijer, Britt; Piehl, Fredrik; Svensson, Mikael

    2010-08-01

    Secondary brain damage following traumatic brain injury in part depends on neuroinflammation, a process where genetic factors may play an important role. We examined the response to a standardized cortical contusion in two different inbred rat strains, Dark Agouti (DA) and Piebald Virol Glaxo (PVG). Both are well characterized in models of autoimmune neuroinflammation, where DA is susceptible and PVG resistant. We found that infiltration of polymorphonuclear granulocytes (PMN) at 3-day postinjury was more pronounced in PVG. DA was more infiltrated by T cells at 3-day postinjury, showed an enhanced glial activation at 7-day postinjury and higher expression of C3 complement at 7-day postinjury. Neurodegeneration, assessed by Fluoro-Jade, was also more pronounced in the DA strain at 30-day postinjury. These results demonstrate differences in the response to cortical contusion injury attributable to genetic influences and suggest a link between injury-induced inflammation and neurodegeneration. Genetic factors that regulate inflammation elicited by brain trauma may be important for the development of secondary brain damage.

  4. Partial lesion of the serotonergic system by a single dose of MDMA results in behavioural disinhibition and enhances acute MDMA-induced social behaviour on the social interaction test.

    Science.gov (United States)

    Ando, Romeo D; Benko, Anita; Ferrington, Linda; Kirilly, Eszter; Kelly, Paul A T; Bagdy, Gyorgy

    2006-06-01

    The acute effects of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) on anxiety-related behaviours were studied using indices of social interaction in Dark Agouti (DA) both drug naive rats and those pretreated with MDMA (15 mg/kg i.p.) 3 weeks earlier. The functional neuroanatomy of these MDMA effects was visualised using 2-deoxyglucose imaging of local cerebral glucose use (LCMRglu), whilst MDMA-induced serotonergic neurotoxicity was measured by radioligand binding with [3H]paroxetine. Acute MDMA alone markedly decreased most typical elements of social interaction but increased adjacent lying, a behaviour that also contains social elements. In animals pre-exposed to MDMA, decreased [3H]paroxetine binding indicated serotonergic terminal depletion, and in these animals significant increases in locomotor activity, exploratory behaviour and aggressive behaviour were found. Both behavioural effects and also the metabolic activation induced by acute MDMA were potentiated in rats previously exposed to the drug. In conclusion, a single dose of MDMA caused marked changes in social behaviour acutely that might be interpreted either as a decrease or increase in anxiety. Three weeks after MDMA a behavioural disinhibition similar to psychomotor agitation, a symptom connected to depression or mania, and a sensitization to the acute effects of MDMA are apparent in both the behavioural and brain metabolic effects of the drug.

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

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    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.

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

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    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.

  7. The melanocortin-1 receptor: red hair and beyond.

    Science.gov (United States)

    Schaffer, J V; Bolognia, J L

    2001-11-01

    Although human pigmentation is genetically complex, to date polymorphism at only 1 locus, the melanocortin-1 receptor (MC1-R), has been associated with physiologic variation in hair and skin color. The MC1-R, a G protein-coupled receptor with 7 transmembrane-spanning domains, plays a key role in determining the type of melanin (eumelanin vs pheomelanin) that is produced within melanocytes. This article begins with an overview of melanocortin receptors, proopiomelanocortin-derived ligands, and the agouti antagonist, with particular focus on their functions in regulating eumelanin and pheomelanin synthesis, including UV-induced melanogenesis. A brief description of mouse-coat-color genetics is then followed by a discussion of human MC1-R variants, which are present in approximately 50% of white populations. We review the increasing evidence that loss-of-function MC1-R mutations largely account for the red hair phenotype in humans (which approximates an autosomal recessive trait) and also have a strong association with fair skin and a decreased ability to tan, with a significant heterozygote effect in individuals without red hair. Finally, we examine recent work showing that loss-of-function MC1-R variants may increase the risk of developing melanoma and nonmelanoma skin cancer beyond their effects on pigmentation phenotype.

  8. 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.

  9. Role of copper accumulation in spontaneous renal carcinogenesis in Long-Evans Cinnamon rats.

    Science.gov (United States)

    Kitaura, K; Chone, Y; Satake, N; Akagi, A; Ohnishi, T; Suzuki, Y; Izumi, K

    1999-04-01

    Spontaneous renal cell tumors in totals of 223 male and female Long-Evans Cinnamon (LEC) rats of 51-120 weeks old, 157 male F344 rats of 51-120 weeks old, and 14 male Long-Evans Agouti (LEA) rats of 51-70 weeks old were examined histologically. The incidences of renal cell tumors increased with age in male and female LEC rats, but no tumors developed in F344 or LEA rats. Dilated atypical tubules of the kidneys were observed at high incidence in aged LEC rats. Copper staining of LEC rat kidneys showed a positive reaction in proximal tubules of the cortex and the outer stripe of the medulla. The renal copper concentration of LEC rats reached a peak in the period of necrotizing hepatitis with renal tubular necrosis, and was higher than that in F344 rats for up to 106 weeks. In contrast, the renal iron concentration of LEC rats was lower than that in F344 rats except in the period of necrotizing hepatitis. Long-term treatment of LEC rats with D-penicillamine, a copper-chelating agent, inhibited accumulation of copper, but not iron, in the kidneys, and inhibited the development of karyomegaly of proximal tubules and dilated atypical tubules. These results suggest that persistent copper accumulation after toxic necrosis of tubules is the major cause of spontaneous renal carcinogenesis in LEC rats.

  10. Immune response to gut Escherichia coli and susceptibility to adjuvant arthritis in the rats.

    Science.gov (United States)

    Kovačević-Jovanović, Vesna; Miletić, Tatjana; Stanojević, Stanislava; Mitić, Katarina; Dimitrijević, Mirjana

    2015-03-01

    We have investigated the humoral immune response to antigens of predominant gut aerobic bacterial strains (i.e. Escherichia coli) over the course of adjuvant arthritis and oil-induced arthritis in two inbred rat strains: Dark Agouti (DA) and Albino Oxford (AO). We report the presence of antibodies specific to proteins of E. coli in molecular weight range between 20-30 kDa in sera of diseased DA rats, and the absence of these antibodies in the sera of AO rats. In DA rats, CFA and IFA provoked a stronger antibody response to E. coli, especially of the IgG2b antibody class. Intramuscular administration of E. coli preceding the adjuvant arthritis induction had no effect on the development and course of disease, as well as on the activation of T cells in the draining inguinal lymph nodes. Higher serum levels of natural and induced IgA antibodies, combined with a higher CD3+CD26+ cell percentage were found in AO rats. The observed correlation between the serologic response to commensal flora and rats' genetic background as a defining factor for arthritis susceptibility may contribute to the process of creating a favorable (or less favorable) milieu for arthritis development.

  11. Anorexia and Impaired Glucose Metabolism in Mice With Hypothalamic Ablation of Glut4 Neurons

    Science.gov (United States)

    Ren, Hongxia; Lu, Taylor Y.; McGraw, Timothy E.

    2015-01-01

    The central nervous system (CNS) uses glucose independent of insulin. Nonetheless, insulin receptors and insulin-responsive glucose transporters (Glut4) often colocalize in neurons (Glut4 neurons) in anatomically and functionally distinct areas of the CNS. The apparent heterogeneity of Glut4 neurons has thus far thwarted attempts to understand their function. To answer this question, we used Cre-dependent, diphtheria toxin–mediated cell ablation to selectively remove basal hypothalamic Glut4 neurons and investigate the resulting phenotypes. After Glut4 neuron ablation, mice demonstrate altered hormone and nutrient signaling in the CNS. Accordingly, they exhibit negative energy balance phenotype characterized by reduced food intake and increased energy expenditure, without locomotor deficits or gross neuronal abnormalities. Glut4 neuron ablation affects orexigenic melanin-concentrating hormone neurons but has limited effect on neuropeptide Y/agouti-related protein and proopiomelanocortin neurons. The food intake phenotype can be partially normalized by GABA administration, suggesting that it arises from defective GABAergic transmission. Glut4 neuron–ablated mice show peripheral metabolic defects, including fasting hyperglycemia and glucose intolerance, decreased insulin levels, and elevated hepatic gluconeogenic genes. We conclude that Glut4 neurons integrate hormonal and nutritional cues and mediate CNS actions of insulin on energy balance and peripheral metabolism. PMID:25187366

  12. Effects of food deprivation on the hypothalamic feeding-regulating peptides gene expressions in serotonin depleted rats.

    Science.gov (United States)

    Yoshimura, Mitsuhiro; Hagimoto, Marina; Matsuura, Takanori; Ohkubo, Junichi; Ohno, Motoko; Maruyama, Takashi; Ishikura, Toru; Hashimoto, Hirofumi; Kakuma, Tetsuya; Yoshimatsu, Hironobu; Terawaki, Kiyoshi; Uezono, Yasuhito; Toyohira, Yumiko; Yanagihara, Nobuyuki; Ueta, Yoichi

    2014-03-01

    We examined the effects of serotonin (5-HT) depletion induced by peripheral injection of 5-HT synthesis inhibitor p-chlorophenylalanine (PCPA) on the expression of feeding-regulating peptides expressions by using in situ hybridization histochemistry in adult male Wistar rats. PCPA pretreatment had no significant effect on basal levels of oxytocin, corticotropin-releasing hormone (CRH), thyrotropin-releasing hormone (TRH), pro-opiomelanocortin (POMC), cocaine and amphetamine-regulated transcript (CART), neuropeptide-Y (NPY), agouti-related protein (AgRP), melanin-concentrating hormone (MCH) or orexin in the hypothalamus. Food deprivation for 48 h caused a significant decrease in CRH, TRH, POMC, and CART, and a significant increase in NPY, AgRP and MCH. After PCPA treatment, POMC and CART did not decrease despite food deprivation. NPY was significantly increased by food deprivation with PCPA, but was attenuated compared to food deprivation without PCPA. These results suggest that the serotonergic system in the hypothalamus may be involved in the gene expression of POMC, CART, and NPY related to feeding behavior.

  13. Effect of Zinc on Appetite Regulatory Peptides in the Hypothalamus of Salmonella-Challenged Broiler Chickens.

    Science.gov (United States)

    Hu, Xiyi; Sheikhahmadi, Ardashir; Li, Xianlei; Wang, Yufeng; Jiao, Hongchao; Lin, Hai; Zhang, Bingkun; Song, Zhigang

    2016-07-01

    The effects of dietary Zinc (Zn) supplementation on the gene expression of appetite regulatory peptides were investigated in Salmonella-infected broiler chickens. Broiler chickens (Arbor Acres, 1 day old) were allocated randomly into 24 pens of 10 birds. The chickens from 12 pens were fed with basal diet and the other with basal diet supplemented with Zn (ZnSO4·H2O, 120 mg/kg). At 5 days of age, the chickens were divided into 4 treatments with 6 pens: basal diet; basal diet and Salmonella challenge; Zn-supplemented diet; Zn-supplemented diet and Salmonella challenge. At 42 days of age, the hypothalamus from 6 chickens per treatment (1 chicken per pen) was individually collected for gene expression determination. Results showed that dietary supplementation of Zn reduced the gene expression of hypothalamic ghrelin and tumor necrosis factor alpha (TNF-α) (P Salmonella infection upregulated the messenger RNA (mRNA) levels of hypothalamic neuropeptide Y (NPY) and TNF-α. Zn supplementation and Salmonella inoculation were significantly correlated with the mRNA levels of toll-like receptor 2-1 (P Salmonella inoculation had significant effect on hypothalamic agouti-related protein, cocaine- and amphetamine-regulated transcript, and pro-opiomelanocortin. This study shows that dietary Zn supplementation promoted orexigenic appetite regulatory peptides and reduced the expression of the inflammatory cytokine TNF-α in the hypothalamus of Salmonella-challenged broilers.

  14. [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.

  15. Changes in Ghrelin-Related Factors in Gastroesophageal Reflux Disease in Rats

    Directory of Open Access Journals (Sweden)

    Miwa Nahata

    2013-01-01

    Full Text Available To examine gastrointestinal hormone profiles and functional changes in gastroesophageal reflux disease (GERD, blood levels of the orexigenic hormone ghrelin were measured in rats with experimentally induced GERD. During the experiment, plasma acyl ghrelin levels in GERD rats were higher than those in sham-operated rats, although food intake was reduced in GERD rats. Although plasma levels of the appetite-suppressing hormone leptin were significantly decreased in GERD rats, no changes were observed in cholecystokinin levels. Repeated administration of rat ghrelin to GERD rats had no effect on the reduction in body weight or food intake. Therefore, these results suggest that aberrantly increased secretion of peripheral ghrelin and decreased ghrelin responsiveness may occur in GERD rats. Neuropeptide Y and agouti-related peptide mRNA expression in the hypothalamus of GERD rats was significantly increased, whereas proopiomelanocortin mRNA expression was significantly decreased compared to that in sham-operated rats. However, melanin-concentrating hormone (MCH and prepro-orexin mRNA expression in the hypothalamus of GERD rats was similar to that in sham-operated rats. These results suggest that although GERD rats have higher plasma ghrelin levels, ghrelin signaling in GERD rats may be suppressed due to reduced MCH and/or orexin synthesis in the hypothalamus.

  16. Anabolic androgenic steroid nandrolone decanoate reduces hypothalamic proopiomelanocortin mRNA levels.

    Science.gov (United States)

    Lindblom, Jonas; Kindlundh, Anna M S; Nyberg, Fred; Bergström, Lena; Wikberg, Jarl E S

    2003-10-03

    Supratherapeutical doses of anabolic androgenic steroids (AASs) have dramatic effects on metabolism in humans, and also inhibit feeding and reduce the rate of body weight gain in rats. In order to test the hypothesis that the AAS metabolic syndrome is accompanied by alterations in the central melanocortin system, we evaluated body weight, food intake and hypothalamic agouti-related protein (AgRP) and proopiomelanocortin (POMC) mRNA levels following administration of different doses of the anabolic androgenic steroid nandrolone decanoate. In order to distinguish changes induced by the steroid treatment per se from those resulting from the reduced food intake and growth rate, we also compared the effect of nandrolone decanoate on AgRP and POMC mRNA expression with both normally fed, and food restricted control groups. We here report that administration of nandrolone specifically reduces arcuate nucleus POMC mRNA levels while not affecting the expression level of AgRP. The effect on POMC expression was not observed in the food restricted controls, excluding the possibility that the observed effect was a mere response to the reduced food intake and body weight. These results raise the possibility that some of the metabolic and behavioural consequences of AAS abuse may be the result of alterations in the melanocortin system.

  17. Development of injury in a rat model of chronic renal allograft rejection: effect of dietary protein restriction.

    Science.gov (United States)

    Bombas, A; Stein-Oakley, A N; Baxter, K; Thomson, N M; Jablonski, P

    1999-01-01

    Non-allogeneic factors such as increased nephron "workload" may contribute to chronic renal allograft rejection. Reducing dietary protein from 20% to 8% was tested in a model of chronic rejection: Dark Agouti kidney to Albino Surgery recipient, "tolerised" by previous donor blood transfusions. Survival, weight gain, serum creatinine concentration and creatinine clearance were similar for both groups at all times. Urinary protein was significantly (P < 0.05) lower in the low-protein (LP) group 1 month after transplantation. After 3 and 6 months, both groups demonstrated mild chronic rejection. After 6 months, tubular atrophy was significantly (P < 0.05) less in the LP group and interstitial fibrosis was marginally reduced. Glomerular hypertrophy, glomerular sclerosis, tubular dilatation, leucocyte infiltration, adhesion molecule expression and TGF-beta1 mRNA expression were similarly increased in both groups. Thus, reducing dietary protein to 8% lowered urinary protein, but did not significantly affect the development of chronic rejection in renal allografts beyond affording a degree of protection from tubulointerstitial damage.

  18. Proliferation of CD8-positive T cells in blood vessels of rat renal allografts.

    Science.gov (United States)

    Grau, V; Fuchs-Moll, G; Wilker, S; Weimer, R; Padberg, W

    2011-09-01

    It is still disputed in which anatomical compartments of allograft recipients T-cells proliferate. After experimental renal transplantation, host monocytes and lymphocytes accumulate in the lumina of graft blood vessels. In this study, we test the hypothesis that T lymphocytes proliferate in the vascular bed of the graft. Kidneys were transplanted in the Dark Agouti to Lewis rat strain combination, an established experimental model for acute rejection. Isogeneic transplantation was performed as a control. Cells in the S-phase of mitosis were detected in situ three days posttransplantation by pulse-labeling with BrdU and by immunohistochemical detection of the proliferating cell nuclear antigen (PCNA). More than 20% of all T-cells in the lumina of allograft blood vessels incorporated BrdU and approximately 30% of them expressed PCNA. In the blood vessels of isografts as well as in other organs of allograft recipients, only few BrdU(+) cells were detected. A majority of the BrdU(+) cells in graft blood vessels expressed CD8. In conclusion, we demonstrate that CD8(+) T lymphocytes proliferate in the lumina of the blood vessels of renal allografts during the onset of acute rejection.

  19. 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.

  20. The arcuate nucleus mediates GLP-1 receptor agonist liraglutide-dependent weight loss.

    Science.gov (United States)

    Secher, Anna; Jelsing, Jacob; Baquero, Arian F; Hecksher-Sørensen, Jacob; Cowley, Michael A; Dalbøge, Louise S; Hansen, Gitte; Grove, Kevin L; Pyke, Charles; Raun, Kirsten; Schäffer, Lauge; Tang-Christensen, Mads; Verma, Saurabh; Witgen, Brent M; Vrang, Niels; Bjerre Knudsen, Lotte

    2014-10-01

    Liraglutide is a glucagon-like peptide-1 (GLP-1) analog marketed for the treatment of type 2 diabetes. Besides lowering blood glucose, liraglutide also reduces body weight. It is not fully understood how liraglutide induces weight loss or to what degree liraglutide acts directly in the brain. Here, we determined that liraglutide does not activate GLP-1-producing neurons in the hindbrain, and liraglutide-dependent body weight reduction in rats was independent of GLP-1 receptors (GLP-1Rs) in the vagus nerve, area postrema, and paraventricular nucleus. Peripheral injection of fluorescently labeled liraglutide in mice revealed the presence of the drug in the circumventricular organs. Moreover, labeled liraglutide bound neurons within the arcuate nucleus (ARC) and other discrete sites in the hypothalamus. GLP-1R was necessary for liraglutide uptake in the brain, as liraglutide binding was not seen in Glp1r(-/-) mice. In the ARC, liraglutide was internalized in neurons expressing proopiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART). Electrophysiological measurements of murine brain slices revealed that GLP-1 directly stimulates POMC/CART neurons and indirectly inhibits neurotransmission in neurons expressing neuropeptide Y (NPY) and agouti-related peptide (AgRP) via GABA-dependent signaling. Collectively, our findings indicate that the GLP-1R on POMC/CART-expressing ARC neurons likely mediates liraglutide-induced weight loss.

  1. Disruption of neural signal transducer and activator of transcription 3 causes obesity, diabetes, infertility, and thermal dysregulation.

    Science.gov (United States)

    Gao, Qian; Wolfgang, Michael J; Neschen, Susanne; Morino, Katsutaro; Horvath, Tamas L; Shulman, Gerald I; Fu, Xin-Yuan

    2004-03-30

    Signal transducer and activator of transcription (STAT)3 is widely expressed in the CNS during development and adulthood. STAT3 has been implicated in the control of neuron/glial differentiation and leptin-mediated energy homeostasis, but the physiological role and degree of involvement of STAT3 in these processes is not defined and controversial because of the lack of a direct genetic model. To address this, we created mice with a neural-specific disruption of STAT3 (STAT3(N-/-)). Surprisingly, homozygous mutants were born at the expected Mendelian ratio without apparent developmental abnormalities but susceptible to neonatal lethality. Mutants that survived the neonatal period were hyperphagic, obese, diabetic, and infertile. Administering a melanocortin-3/4 receptor agonist abrogated the hyperphagia and hypothalamic immunohistochemistry showed a marked reduction in proopiomelanocortin with an increase in neuropeptide Y and agouti-related protein. Mutants had reduced energy expenditure and became hypothermic after fasting or cold stress. STAT3(N-/-) mice are hyperleptinemic, suggesting a leptin-resistant condition. Concomitant with neuroendocrine defects such as decreased linear growth and infertility with accompanying increased corticosterone levels, this CNS knockout recapitulates the unique phenotype of db/db and ob/ob obese models and distinguishes them from other genetic models of obesity. Thus, STAT3 in the CNS plays essential roles in the regulation of energy homeostasis and reproduction.

  2. Food restriction normalizes chylomicron remnant metabolism in murine models of obesity as assessed by a novel stable isotope breath test.

    Science.gov (United States)

    Martins, Ian J; Tran, J M L; Redgrave, Trevor G

    2002-02-01

    Evidence is increasing that defective metabolism of postprandial remnants of triglyceride-rich lipoproteins contributes to atherogenesis. In obesity, postprandial lipemia is increased by mechanisms that are not currently established. In the present study, a recently developed (13)CO(2) breath test was used to assess the metabolism of chylomicron remnants (CR) in obese mice. Six murine obese models ob/ob, fat/fat, New Zealand Obese (NZO), db/db, gold thioglucose (GTG)-treated and agouti (A(y)) were studied. All obese mice were hyperphagic and their breath test metabolism was markedly impaired (P obese models such as db/db were diabetic, our data suggest that the defective breath test was independent of diabetes because all obese and diabetic models responded similarly to food restriction. Impaired hepatic catabolism of CR was excluded as a cause of the abnormal breath tests. In summary, the impairment (P < 0.05) in remnant metabolism as assessed by the breath test in obese mice was corrected by food restriction, associated with improvements in plasma glucose, triglyceride and cholesterol levels.

  3. Obesity modulates the expression of haptoglobin in the white adipose tissue via TNFalpha.

    Science.gov (United States)

    Chiellini, Chiara; Bertacca, Anna; Novelli, Silvia E; Görgün, Cem Z; Ciccarone, Annamaria; Giordano, Antonio; Xu, Haiyan; Soukas, Alexander; Costa, Mario; Gandini, Daniele; Dimitri, Roberto; Bottone, Pietro; Cecchetti, Paolo; Pardini, Ennia; Perego, Lucia; Navalesi, Renzo; Folli, Franco; Benzi, Luca; Cinti, Saverio; Friedman, Jeffrey M; Hotamisligil, Gökhan S; Maffei, Margherita

    2002-02-01

    Increase in adipose mass results in obesity and modulation of several factors in white adipose tissue (WAT). Two important examples are tumor necrosis factor alpha (TNFalpha) and leptin, both of which are upregulated in adipose tissue in obesity. In order to isolate genes differentially expressed in the WAT of genetically obese db/db mice compared to their lean littermates, we performed RNA fingerprinting and identified haptoglobin (Hp), which is significantly upregulated in the obese animals. Hp is a glycoprotein induced by a number of cytokines, LPS (Lipopolysaccharide), and more generally by inflammation. A significant upregulation of WAT Hp expression was also evident in several experimental obese models including the yellow agouti (/) A(y), ob/ob and goldthioglucose-treated mice (10-, 8-, and 7-fold, respectively). To identify the potential signals for an increase in Hp expression in obesity, we examined leptin and TNFalpha in vivo. Wild type animals treated with recombinant leptin did not show any alteration in WAT Hp expression compared to controls that were food restricted to the level of intake of the treated animals. On the other hand, Hp expression was induced in mice transgenically expressing TNFalpha in adipose tissue. Finally, a significant downregulation of WAT Hp mRNA was observed in ob/ob mice deficient in TNFalpha function, when compared to the ob/ob controls. These results demonstrate that haptoglobin expression in WAT is increased in obesity in rodents and TNFalpha is an important signal for this regulation.

  4. The mahogany protein is a receptor involved in suppression of obesity.

    Science.gov (United States)

    Nagle, D L; McGrail, S H; Vitale, J; Woolf, E A; Dussault, B J; DiRocco, L; Holmgren, L; Montagno, J; Bork, P; Huszar, D; Fairchild-Huntress, V; Ge, P; Keilty, J; Ebeling, C; Baldini, L; Gilchrist, J; Burn, P; Carlson, G A; Moore, K J

    1999-03-11

    Genetic studies have shown that mutations within the mahogany locus suppress the pleiotropic phenotypes, including obesity, of the agouti-lethal-yellow mutant. Here we identify the mahogany gene and its product; this study, to our knowledge, represents the first positional cloning of a suppressor gene in the mouse. Expression of the mahogany gene is broad; however, in situ hybridization analysis emphasizes the importance of its expression in the ventromedial hypothalamic nucleus, a region that is intimately involved in the regulation of body weight and feeding. We present new genetic studies that indicate that the mahogany locus does not suppress the obese phenotype of the melanocortin-4-receptor null allele or those of the monogenic obese models (Lep(db), tub and Cpe(fat)). However, mahogany can suppress diet-induced obesity, the mechanism of which is likely to have implications for therapeutic intervention in common human obesity. The amino-acid sequence of the mahogany protein suggests that it is a large, single-transmembrane-domain receptor-like molecule, with a short cytoplasmic tail containing a site that is conserved between Caenorhabditis elegans and mammals. We propose two potential, alternative modes of action for mahogany: one draws parallels with the mechanism of action of low-affinity proteoglycan receptors such as fibroblast growth factor and transforming growth factor-beta, and the other suggests that mahogany itself is a signalling receptor.

  5. Pulmonary Immune Responses to Aspergillus Fumigatus in Rats

    Institute of Scientific and Technical Information of China (English)

    MIRKOV Ivana; EL-MUZGHI Amal Atia Mhfuod; DJOKIC Jelena; NINKOV Marina; POPOV ALEKSANDROV Aleksandra; GLAMOCLIJA Jasmina; KATARANOVSKI Milena

    2014-01-01

    Objective To evaluate immunologic mechanisms underlying Aspergillus fumigatus pulmonary infections in immunocompetent Dark Agouti (DA) and Albino Oxford (AO) rats recognized as being susceptible to some inflammatory diseases in different manners. Methods Lung fungal burden (quantitative colony forming units, CFU, assay), leukocyte infiltration (histology, cell composition) and their function (phagocytosis, oxidative activity, CD11b adhesion molecule expression) and cytokine interferon-γ(IFN-γ) and interleukin-17 and-4 (IL-17 and IL-4) lung content were evaluated following infection (intratracheally, 1x107 conidia). Results Slower reduction of fungal burden was observed in AO rats in comparison with that in DA rats, which was coincided with less intense histologically evident lung cell infiltration and leukocyte recovery as well as lower level of most of the their activities including intracellular myeloperoxidase activity, the capacity of nitroblue tetrazolium salt reduction and CD11b adhesion molecule expression (except for phagocytosis of conidia) in these rats. Differential patterns of changes in proinflammatory cytokine levels (unchanged levels of IFN-γand transient increase of IL-17 in AO rats vs continuous increase of both cytokines in DA rats) and unchanged levels of IL-4 were observed. Conclusion Genetically-based differences in the pattern of antifungal lung leukocyte activities and cytokine milieu, associated with differential efficiency of fungal elimination might be useful in the future use of rat models in studies of pulmonary aspergillosis.

  6. 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.

  7. 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.

  8. Ex vivo intracoronary gene transfer of adeno-associated virus 2 leads to superior transduction over serotypes 8 and 9 in rat heart transplants.

    Science.gov (United States)

    Raissadati, Alireza; Jokinen, Janne J; Syrjälä, Simo O; Keränen, Mikko A I; Krebs, Rainer; Tuuminen, Raimo; Arnaudova, Ralica; Rouvinen, Eeva; Anisimov, Andrey; Soronen, Jarkko; Pajusola, Katri; Alitalo, Kari; Nykänen, Antti I; Lemström, Karl

    2013-11-01

    Heart transplant gene therapy requires vectors with long-lasting gene expression, high cardiotropism, and minimal pathological effects. Here, we examined transduction properties of ex vivo intracoronary delivery of adeno-associated virus (AAV) serotype 2, 8, and 9 in rat syngenic and allogenic heart transplants. Adult Dark Agouti (DA) rat hearts were intracoronarily perfused ex vivo with AAV2, AAV8, or AAV9 encoding firefly luciferase and transplanted heterotopically into the abdomen of syngenic DA or allogenic Wistar-Furth (WF) recipients. Serial in vivo bioluminescent imaging of syngraft and allograft recipients was performed for 6 months and 4 weeks, respectively. Grafts were removed for PCR-, RT-PCR, and luminometer analysis. In vivo bioluminescent imaging of recipients showed that AAV9 induced a prominent and stable luciferase activity in the abdomen, when compared with AAV2 and AAV8. However, ex vivo analyses revealed that intracoronary perfusion with AAV2 resulted in the highest heart transplant transduction levels in syngrafts and allografts. Ex vivo intracoronary delivery of AAV2 resulted in efficient transgene expression in heart transplants, whereas intracoronary AAV9 escapes into adjacent tissues. In terms of cardiac transduction, these results suggest AAV2 as a potential vector for gene therapy in preclinical heart transplants studies, and highlight the importance of delivery route in gene transfer studies.

  9. 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.

  10. Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs) in the Brain-Adipocyte Axis.

    Science.gov (United States)

    Geloneze, Bruno; de Lima-Júnior, José Carlos; Velloso, Lício A

    2017-02-23

    The complexity of neural circuits that control food intake and energy balance in the hypothalamic nuclei explains some of the constraints involved in the prevention and treatment of obesity. Two major neuronal populations present in the arcuate nucleus control caloric intake and energy expenditure: one population co-expresses orexigenic agouti-related peptide (AgRP) and neuropeptide Y and the other expresses the anorexigenic anorectic neuropeptides proopiomelanocortin and cocaine- and amphetamine-regulated transcript (POMC/CART). In addition to integrating signals from neurotransmitters and hormones, the hypothalamic systems that regulate energy homeostasis are affected by nutrients. Fat-rich diets, for instance, elicit hypothalamic inflammation (reactive activation and proliferation of microglia, a condition named gliosis). This process generates resistance to the anorexigenic hormones leptin and insulin, contributing to the genesis of obesity. Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) have increasingly been used to treat type 2 diabetes mellitus. One compound (liraglutide) was recently approved for the treatment of obesity. Although most studies suggest that GLP-1RAs promote weight loss mainly due to their inhibitory effect on food intake, other central effects that have been described for native GLP-1 and some GLP-1RAs in rodents and humans encourage future clinical trials to explore additional mechanisms that potentially underlie the beneficial effects observed with this drug class. In this article we review the most relevant data exploring the mechanisms involved in the effects of GLP-1RAs in the brain-adipocyte axis.

  11. Effects of fluoxetine administration on hypothalamic melanocortin system in obese Zucker rats.

    Science.gov (United States)

    Churruca, I; Portillo, M P; Casis, L; Gutiérrez, A; Macarulla, M T; Echevarría, E

    2008-06-01

    The aim of the present work was to study the potential involvement of melanocortin system in the anorectic mechanism of fluoxetine, a selective serotonin reuptake inhibitors, in obese Zucker rats. Male obese Zucker (fa/fa) rats were administered fluoxetine (10 mg/kg; i.p.) daily for two weeks. The control group was given 0.9% NaCl solution. RT-PCR for pro-opiomelanocortin (POMC), Agouti gene related peptide (AgRP) and melanocortin receptor 4 (MC4-R) in the hypothalamus, as well as regional immunostaining for alpha-melanocyte stimulating hormone (alpha-MSH) and MC4-R were carried out. Fluoxetine administration increased POMC expression and reduced MC4-R expression in the hypothalamus, without changes in AgRP mRNA levels. Moreover, an increase in the numbers of alpha-MSH positively immunostained neural cells in the hypothalamic arcuate nucleus (ARC), as well as a significant decrease in the numbers of neural cells positively immunostained for MC4-R in the paraventricular nucleus (PVN), without changes in lateral hypothalamic area (LHA), were observed. These results suggest the involvement of alpha-MSH in central fluoxetine anorectic action.

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

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    Dominique Muschter

    Full Text Available 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(-6 M 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.

  13. Recurrent evolution of melanism in South American felids.

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    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.

  14. 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.

  15. An intrinsic gut leptin-melanocortin pathway modulates intestinal microsomal triglyceride transfer protein and lipid absorption.

    Science.gov (United States)

    Iqbal, Jahangir; Li, Xiaosong; Chang, Benny Hung-Junn; Chan, Lawrence; Schwartz, Gary J; Chua, Streamson C; Hussain, M Mahmood

    2010-07-01

    Fat is delivered to tissues by apoB-containing lipoproteins synthesized in the liver and intestine with the help of an intracellular chaperone, microsomal triglyceride transfer protein (MTP). Leptin, a hormone secreted by adipose tissue, acts in the brain and on peripheral tissues to regulate fat storage and metabolism. Our aim was to identify the role of leptin signaling in MTP regulation and lipid absorption using several mouse models deficient in leptin receptor (LEPR) signaling and downstream effectors. Mice with spontaneous LEPR B mutations or targeted ablation of LEPR B in proopiomelanocortin (POMC) or agouti gene related peptide (AGRP) expressing cells had increased triglyceride in plasma, liver, and intestine. Furthermore, melanocortin 4 receptor (MC4R) knockout mice expressed a similar triglyceride phenotype, suggesting that leptin might regulate intestinal MTP expression through the melanocortin pathway. Mechanistic studies revealed that the accumulation of triglyceride in the intestine might be secondary to decreased expression of MTP and lipid absorption in these mice. Surgical and chemical blockade of vagal efferent outflow to the intestine in wild-type mice failed to alter the triglyceride phenotype, demonstrating that central neural control mechanisms were likely not involved in the observed regulation of intestinal MTP. Instead, we found that enterocytes express LEPR, POMC, AGRP, and MC4R. We propose that a peripheral, local gut signaling mechanism involving LEPR B and MC4R regulates intestinal MTP and controls intestinal lipid absorption.

  16. 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.

  17. 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.

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

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    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.

  19. Grape seed extract protects IEC-6 cells from chemotherapy-induced cytotoxicity and improves parameters of small intestinal mucositis in rats with experimentally-induced mucositis.

    Science.gov (United States)

    Cheah, Ker Y; Howarth, Gordon S; Yazbeck, Roger; Wright, Tessa H; Whitford, Eleanor J; Payne, Caroline; Butler, Ross N; Bastian, Susan E P

    2009-02-01

    Mucositis is a common side-effect of high-dose chemotherapy regimens. Grape seed extract (GSE) represents a rich source of proanthocyanidins with the potential to decrease oxidative damage and inflammation within the gastrointestinal tract. We evaluated GSE for its capacity to decrease the severity of chemotherapy-induced mucositis in vitro and in vivo. In vitro: GSE was administered to IEC-6 intestinal epithelial cells prior to damage induced by 5-Fluorouracil (5-FU). Cell viability was determined by neutral red assay. In vivo: Female Dark Agouti rats (130-180 g) were gavaged with 1 ml GSE (400 mg/kg) daily (day 3-11) and received 5-FU (150 mg/kg) by intraperitoneal (i.p.) injection on day nine to induce mucositis. Rats were sacrificed at day 12 and intestinal tissues collected for myeloperoxidase and sucrase activity assays and histological analyses. Statistical analysis was performed by one-way ANOVA. GSE prevented the decrease in IEC-6 cell viability induced by 5-FU (p IEC-6 cells from 5-FU-induced cytotoxicity and ameliorated intestinal damage induced by 5-FU in rats. GSE may represent a promising prophylactic adjunct to conventional chemotherapy for preventing intestinal mucositis.

  20. Interactions of Circadian Rhythmicity, Stress and Orexigenic Neuropeptide Systems: Implications for Food Intake Control

    Science.gov (United States)

    Blasiak, Anna; Gundlach, Andrew L.; Hess, Grzegorz; Lewandowski, Marian H.

    2017-01-01

    Many physiological processes fluctuate throughout the day/night and daily fluctuations are observed in brain and peripheral levels of several hormones, neuropeptides and transmitters. In turn, mediators under the “control” of the “master biological clock” reciprocally influence its function. Dysregulation in the rhythmicity of hormone release as well as hormone receptor sensitivity and availability in different tissues, is a common risk-factor for multiple clinical conditions, including psychiatric and metabolic disorders. At the same time circadian rhythms remain in a strong, reciprocal interaction with the hypothalamic-pituitary-adrenal (HPA) axis. Recent findings point to a role of circadian disturbances and excessive stress in the development of obesity and related food consumption and metabolism abnormalities, which constitute a major health problem worldwide. Appetite, food intake and energy balance are under the influence of several brain neuropeptides, including the orexigenic agouti-related peptide, neuropeptide Y, orexin, melanin-concentrating hormone and relaxin-3. Importantly, orexigenic neuropeptide neurons remain under the control of the circadian timing system and are highly sensitive to various stressors, therefore the potential neuronal mechanisms through which disturbances in the daily rhythmicity and stress-related mediator levels contribute to food intake abnormalities rely on reciprocal interactions between these elements. PMID:28373831

  1. Effects of hypothalamic neurodegeneration on energy balance.

    Directory of Open Access Journals (Sweden)

    Allison Wanting Xu

    2005-12-01

    Full Text Available Normal aging in humans and rodents is accompanied by a progressive increase in adiposity. To investigate the role of hypothalamic neuronal circuits in this process, we used a Cre-lox strategy to create mice with specific and progressive degeneration of hypothalamic neurons that express agouti-related protein (Agrp or proopiomelanocortin (Pomc, neuropeptides that promote positive or negative energy balance, respectively, through their opposing effects on melanocortin receptor signaling. In previous studies, Pomc mutant mice became obese, but Agrp mutant mice were surprisingly normal, suggesting potential compensation by neuronal circuits or genetic redundancy. Here we find that Pomc-ablation mice develop obesity similar to that described for Pomc knockout mice, but also exhibit defects in compensatory hyperphagia similar to what occurs during normal aging. Agrp-ablation female mice exhibit reduced adiposity with normal compensatory hyperphagia, while animals ablated for both Pomc and Agrp neurons exhibit an additive interaction phenotype. These findings provide new insight into the roles of hypothalamic neurons in energy balance regulation, and provide a model for understanding defects in human energy balance associated with neurodegeneration and aging.

  2. Novel hypophysiotropic AgRP2 neurons and pineal cells revealed by BAC transgenesis in zebrafish

    Science.gov (United States)

    Shainer, Inbal; Buchshtab, Adi; Hawkins, Thomas A.; Wilson, Stephen W.; Cone, Roger D.; Gothilf, Yoav

    2017-01-01

    The neuropeptide agouti-related protein (AgRP) is expressed in the arcuate nucleus of the mammalian hypothalamus and plays a key role in regulating food consumption and energy homeostasis. Fish express two agrp genes in the brain: agrp1, considered functionally homologous with the mammalian AgRP, and agrp2. The role of agrp2 and its relationship to agrp1 are not fully understood. Utilizing BAC transgenesis, we generated transgenic zebrafish in which agrp1- and agrp2-expressing cells can be visualized and manipulated. By characterizing these transgenic lines, we showed that agrp1-expressing neurons are located in the ventral periventricular hypothalamus (the equivalent of the mammalian arcuate nucleus), projecting throughout the hypothalamus and towards the preoptic area. The agrp2 gene was expressed in the pineal gland in a previously uncharacterized subgroup of cells. Additionally, agrp2 was expressed in a small group of neurons in the preoptic area that project directly towards the pituitary and form an interface with the pituitary vasculature, suggesting that preoptic AgRP2 neurons are hypophysiotropic. We showed that direct synaptic connection can exist between AgRP1 and AgRP2 neurons in the hypothalamus, suggesting communication and coordination between AgRP1 and AgRP2 neurons and, therefore, probably also between the processes they regulate. PMID:28317906

  3. Use of FK506 and bone marrow mesenchymal stem cells for rat hind limb allografts

    Institute of Scientific and Technical Information of China (English)

    Youxin Song; Zhujun Wang; Zhixue Wang; Hong Zhang; Xiaohui Li; Bin Chen

    2012-01-01

    Dark Agouti rat donor hind limbs were orthotopically transplanted into Lewis rat recipients to verify the effects of bone marrow mesenchymal stem cells on neural regeneration and functional recovery of allotransplanted limbs in the microenvironment of immunotolerance. bone marrow mesenchymal stem cells were intramuscularly (gluteus maximus) injected with FK506 (tacrolimus) daily, and were transplanted to the injured nerves. Results indicated that the allograft group not receiving therapy showed severe rejection, with transplanted limbs detaching at 10 days after transplantation with complete necrosis. The number of myelinated axons and Schwann cells in the FK506 and FK506 + bone marrow mesenchymal stem cells groups were significantly increased. We observed a lesser degree of gastrocnemius muscle degeneration, and increased polymorphic fibers along with other pathological changes in the FK506 + bone marrow mesenchymal stem cells group. The FK506 + bone marrow mesenchymal stem cells group showed significantly better recovery than the autograft and FK506 groups. The results demonstrated that FK506 improved the immune microenvironment. FK506 combined with bone marrow mesenchymal stem cells significantly promoted sciatic nerve regeneration, and improved sensory recovery and motor function in hind limb allotransplant.

  4. Phenotypic Characterization of LEA Rat: A New Rat Model of Nonobese Type 2 Diabetes

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    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.

  5. 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.

  6. 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

    2017-01-01

    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 prior to 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 pre-consummatory modulation of ARCAgRP neurons. In a manner reciprocal to ARCAgRP neurons, ARC-projecting leptin receptor (LepR)-expressing GABAergic DMH neurons exhibit rapid activation upon availability of food that additionally reflects the relative value of the food. Thus, DMHLepR 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. PMID:27643429

  7. 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.

  8. Neuroendorine and epigentic mechanisms subserving autonomic imbalance and HPA dysfunction in the metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Erwin eLemche

    2016-04-01

    Full Text Available 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 signalling 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.

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. High-fat diet-induced met-hemoglobin formation in rats prone (WOKW) or resistant (DA) to the metabolic syndrome: effect of CoQ10 supplementation.

    Science.gov (United States)

    Orlando, Patrick; Silvestri, Sonia; Brugè, Francesca; Tiano, Luca; Kloting, Ingrid; Falcioni, Giancarlo; Polidori, Carlo

    2014-01-01

    The aim of this study was to evaluate the effects of a high-fat diet (HFD) on oxidative indexes in WistarOttawaKarlsburg W (WOKW) rats used as a model of metabolic syndrome in comparison with Dark Agouti (DA) rats used as a control strain. This syndrome is defined by the occurrence of two or more risk factors including obesity, hypertension, dyslipidemia, and insulin resistance. Forty rats were used in the study and the effect of HFD was evaluated in terms of body weight and both hemoglobin and CoQ oxidative status. Moreover, 16 rats (8 of each strain) were supplemented with 3 mg/100 g b.w. of CoQ10 for 1 month in view of its beneficial properties in cardiovascular disease due to its antioxidant activity in the lipid environment. HFD promoted an increase in body weight, in particular in WOKW males, and in the methemoglobin (met-Hb) index in both strains. Moreover, HFD promoted endogenous CoQ10 oxidation. CoQ10 supplementation was able to efficiently counteract the HFD pro-oxidant effects, preventing met-Hb formation and CoQ oxidation.

  14. Production of Brown/Yellow Patches in the SLC7A11 Transgenic Sheep via Testicular Injection of Transgene

    Institute of Scientific and Technical Information of China (English)

    Xin He; Hongtao Li; Zhiyong Zhou; Zongsheng Zhao; Wei Li

    2012-01-01

    The gene,SLC7A11,which encodes the solute carrier family 7 member 11 (anionic amino acid transporter light chain,xCT),has been reported to be implicated in multiple processes such as in pheomelanin production,cell proliferation and migration,Kaposi's sarcoma herpesvirus (KSHV) entry into the host cells,learning and memory.Its involvement in cancer cell proliferation and metastasis has been widely studied.Its role in pheomelanogenesis is likely conserved in sheep.The full-length cDNA of sheep SLC7A11 was cloned from sheep skin fibroblasts for evaluating its role in regulating sheep coat color.The complete open reading frame of sheep xCT (sxCT) is 1512 bp in length,encoding a 503 amino acid polypeptide.We explored its function on pheomelanogenesis in vitro and in vivo.In the melan-a non-agouti mouse melanocytes that mainly produce eumelanin,overexpressed sxCT reduced the content of eumelanin.Using a testicular injection transgenic method,sxCT-transgenic sheep were generated and exhibited patches of brown/yellow coat,suggesting that sxCT can be selectively expressed to increase the pheomelanin production in wool.Our studies suggest that testicular injection of transgene can be used to genetically modify sheep coat color.

  15. Feeding behavior and gene expression of appetite-related neuropeptides in mice lacking for neuropeptide Y Y5 receptor subclass

    Institute of Scientific and Technical Information of China (English)

    Hiroshi Higuchi; Takeshi Nild; Tomohiro Shiiya

    2008-01-01

    Neuropeptide Y (NPY) is a potent neurotransmitter for feeding. Besides NPY, orexigenic neuropeptides such as agouti-related protein (AgRP), and anorexi-genic neuropeptides such as a-melatonin stimulating hormone (MSH) and cocaine-amphetamine-regulated transcript (CART) are also involved in central feeding regulation. During fasting, NPY and AgRP gene expres-sions are up-regulated and POMC and CART gene ex-pressions are down-regulated in hypothalamus. Based on the network of peptidergic neurons, the former are involved in positive feeding regulation, and the latter are involved in negative feeding, which exert these feeding-regulated peptides especially in paraventricular nucleus (PVN). To clarify the compensatory mecha-nism of knock-out of NPY system on feeding, change in gene expressions of appetite-related neuropeptides and the feeding behavior was studied in NPY Y5-KO mice. Food intake was increased in Y5-KO mice. Fast-ing increased the amounts of food and water intake in the KO mice more profoundly. These data indicated the compensatory phenomenon of feeding behavior in YS-KO mice. RT-PCR and [SH suggested that the compensation of feeding is due to change in gene ex-pressions of AgRP, CART and POMC in hypothalamus. Thus, these findings indicated that the compensatory mechanism involves change in POMC/CART gene ex-pression in arcuate nucleus (ARC). The POMC/CART gene expression is important for central compensatory regulation in feeding behavior.

  16. Acute heat stress up-regulates neuropeptide Y precursor mRNA expression and alters brain and plasma concentrations of free amino acids in chicks.

    Science.gov (United States)

    Ito, Kentaro; Bahry, Mohammad A; Hui, Yang; Furuse, Mitsuhiro; Chowdhury, Vishwajit S

    2015-09-01

    Heat stress causes an increase in body temperature and reduced food intake in chickens. Several neuropeptides and amino acids play a vital role in the regulation of food intake. However, the responses of neuropeptides and amino acids to heat-stress-induced food-intake regulation are poorly understood. In the current study, the hypothalamic mRNA expression of some neuropeptides related to food intake and the content of free amino acids in the brain and plasma was examined in 14-day-old chicks exposed to a high ambient temperature (HT; 40±1 °C for 2 or 5 h) or to a control thermoneutral temperature (CT; 30±1 °C). HT significantly increased rectal temperature and plasma corticosterone level and suppressed food intake. HT also increased the expression of neuropeptide Y (NPY) and agouti-signaling protein (ASIP) precursor mRNA, while no change was observed in pro-opiomelanocortin, cholecystokinin, ghrelin, or corticotropin-releasing hormone precursor mRNA. It was further found that the diencephalic content of free amino acids - namely, tryptophan, leucine, isoleucine, valine and serine - was significantly higher in HT chicks with some alterations in their plasma amino acids in comparison with CT chicks. The induction of NPY and ASIP expression and the alteration of some free amino acids during HT suggest that these changes can be the results or causes the suppression of food intake.

  17. 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.

  18. Transgenic n-3 PUFAs enrichment leads to weight loss via modulating neuropeptides in hypothalamus.

    Science.gov (United States)

    Ma, Shuangshuang; Ge, Yinlin; Gai, Xiaoying; Xue, Meilan; Li, Ning; Kang, Jingxuan; Wan, Jianbo; Zhang, Jinyu

    2016-01-12

    Body weight is related to fat mass, which is associated with obesity. Our study explored the effect of fat-1 gene on body weight in fat-1 transgenic mice. In present study, we observed that the weight/length ratio of fat-1 transgenic mice was lower than that of wild-type mice. The serum levels of triglycerides (TG), cholesterol (CT), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c) and blood glucose (BG) in fat-1 transgenic mice were all decreased. The weights of peri-bowels fat, perirenal fat and peri-testicular fat in fat-1 transgenic mice were reduced. We hypothesized that increase of n-3 PUFAs might alter the expression of hypothalamic neuropeptide genes and lead to loss of body weight in fat-1 transgenic mice. Therefore, we measured mRNA levels of appetite neuropeptides, Neuropeptide Y (NPY), Agouti-related peptides (AgRP), Proopiomelanocortin (POMC), Cocaine and amphetamine regulated transcript (CART), ghrelin and nesfatin-1 in hypothalamus by real-time PCR. Compared with wild-type mice, the mRNA levels of CART, POMC and ghrelin were higher, while the mRNA levels of NPY, AgRP and nesfatin-1 were lower in fat-1 transgenic mice. The results indicate that fat-1 gene or n-3 PUFAs participates in regulation of body weight, and the mechanism of this phenomenon involves the expression of appetite neuropeptides and lipoproteins in fat-1 transgenic mice.

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

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    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.

  20. Expression profile of hypothalamic neuropeptides in chicken lines selected for high or low residual feed intake.

    Science.gov (United States)

    Sintubin, P; Greene, E; Collin, A; Bordas, A; Zerjal, T; Tesseraud, S; Buyse, J; Dridi, S

    2014-08-01

    The R(+) and R(-) chicken lines have been divergently selected for high (R(+)) or low (R(-)) residual feed intake. For the same body weight and egg production, the R(+) chickens consume 40% more food than their counterparts R(-) lines. In the present study we sought to determine the hypothalamic expression profile of feeding-related neuropeptides in these lines maintained under fed or food-deprived conditions. In the fed condition, the suppressor of cytokine signaling 3 (SOCS3) was 17-fold lower (Pneuropeptide Y and agouti-related peptide were more responsive, with higher significant levels in the R(+) compared to R(-) chickens, while no significant differences were seen for the anorexigenic neuropeptides pro-opiomelanocortin and corticotropin releasing hormone. Interestingly, C-reactive protein, adiponectin receptor 1 and ghrelin receptor gene expression were significantly higher (12-, 2- and 3-folds, respectively), however ghrelin and melanocortin 5 receptor mRNA levels were lower (4- and 2-folds, P=0.05 and P=0.03, respectively) in R(+) compared to R(-) animals. We identified several key feeding-related genes that are differently expressed in the hypothalamus of R(+) and R(-) chickens and that might explain the difference in feed intake observed between the two lines.

  1. Hypothalamic neuropeptides and the regulation of appetite.

    Science.gov (United States)

    Parker, Jennifer A; Bloom, Stephen R

    2012-07-01

    Neuropeptides released by hypothalamic neurons play a major role in the regulation of feeding, acting both within the hypothalamus, and at other appetite regulating centres throughout the brain. Where classical neurotransmitters signal only within synapses, neuropeptides diffuse over greater distances affecting both nearby and distant neurons expressing the relevant receptors, which are often extrasynaptic. As well as triggering a behavioural output, neuropeptides also act as neuromodulators: altering the response of neurons to both neurotransmitters and circulating signals of nutrient status. The mechanisms of action of hypothalamic neuropeptides with established roles in feeding, including melanin-concentrating hormone (MCH), the orexins, α-melanocyte stimulating hormone (α-MSH), agouti-gene related protein (AgRP), neuropeptide Y, and oxytocin, are reviewed in this article, with emphasis laid on both their effects on appetite regulating centres throughout the brain, and on examining the evidence for their physiological roles. In addition, evidence for the involvement of several putative appetite regulating hypothalamic neuropeptides is assessed including, ghrelin, cocaine and amphetamine-regulated transcript (CART), neuropeptide W and the galanin-like peptides. This article is part of a Special Issue entitled 'Central control of Food Intake'.

  2. 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.

  3. 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.

  4. Interactions between SNP Alleles at Multiple Loci Contribute to Skin Color Differences between Caucasoid and Mongoloid Subjects

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    Sumiko Anno, Takashi Abe, Takushi Yamamoto

    2008-01-01

    Full Text Available This study aimed to identify single nucleotide polymorphism (SNP alleles at multiple loci associated with racial differences in skin color using SNP genotyping. A total of 122 Caucasians in Toledo, Ohio and 100 Mongoloids in Japan were genotyped for 20 SNPs in 7 candidate genes, encoding the Agouti signaling protein (ASIP, tyrosinase-related protein 1 (TYRP1, tyrosinase (TYR, melanocortin 1 receptor (MC1R, oculocutaneous albinism II (OCA2, microphthalmia-associated transcription factor (MITF, and myosin VA (MYO5A. Data were used to analyze associations between the 20 SNP alleles using linkage disequilibrium (LD. Combinations of SNP alleles were jointly tested under LD for associations with racial groups by performing a χ2 test for independence. Results showed that SNP alleles at multiple loci can be considered the haplotype that contributes to significant differences between the two population groups and suggest a high probability of LD. Confirmation of these findings requires further study with other ethnic groups to analyze the associations between SNP alleles at multiple loci and skin color variation among races.

  5. Defective copper binding to apo-ceruloplasmin in a rat model and patients with Wilson's disease.

    Science.gov (United States)

    Kojimahara, N; Nakabayashi, H; Shikata, T; Esumi, M

    1995-06-01

    To examine the mechanism of decrease in serum ceruloplasmin (Cp) in Long-Evans Cinnamon (LEC) rats, a proposed model of Wilson's disease, we analyzed Cp products at the stages of transcription and translation. Northern blot analysis and immunoblot analysis showed that the level and the molecular size of Cp mRNA and protein in LEC rats were similar to those in control Long-Evans-Agouti (LEA) rats. However, the ferroxidase activity of Cp was significantly decreased in LEC rats. We separated serum Cp into two forms by native polyacrylamide gel electrophoresis with pH modification: one was a holo-Cp with copper and ferroxidase activity, and the other was an inactive apo-Cp without copper. Holo-Cp was the predominant form in LEA rats and normal humans, whereas apo-Cp was the major form in LEC rats and patients with Wilson's disease. The cosegregation of apo-Cp predominance with the disease in LEC rats was analyzed using backcross rats. Apo-Cp was dominant in 8 of 11 offspring with disease but in none of 19 normal offspring. These results indicate that a genetic disturbance of copper binding to apo-Cp may be closely associated with the pathogenesis in LEC rats, and probably in Wilson's disease.

  6. Spontaneous hepatic copper accumulation in Long-Evans Cinnamon rats with hereditary hepatitis. A model of Wilson's disease.

    Science.gov (United States)

    Li, Y; Togashi, Y; Sato, S; Emoto, T; Kang, J H; Takeichi, N; Kobayashi, H; Kojima, Y; Une, Y; Uchino, J

    1991-05-01

    Long-Evans Cinnamon (LEC) rats, an inbred strain of a mutant rat isolated from Long-Evans rats, develop hereditary hepatitis. To elucidate the role of copper metabolism in the development of the hepatitis in LEC rats, we examined the copper concentration in the tissues and serum levels of copper and ceruloplasmin. Copper concentration in the liver of LEC rats was over 40 times that of normal Long-Evans Agouti (LEA) rats, while the serum ceruloplasmin and copper concentrations in LEC rats decreased significantly. The hepatocytes of LEC rats show steatosis in cytoplasm and pleomorphism of mitochondria, resembling the histologic features of the liver in Wilson's disease. These findings suggest that the hereditary hepatitis in LEC rats is closely associated with copper toxicity, and may be dealing with a rat form of Wilson's disease. Thus the LEC rats will provide a unique and useful animal model for clarifying the mechanism and for developing treatment strategies for Wilson's disease and other abnormal copper metabolism in humans.

  7. 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.

  8. Triennial Growth Symposium: neural regulation of feed intake: modification by hormones, fasting, and disease.

    Science.gov (United States)

    Sartin, J L; Whitlock, B K; Daniel, J A

    2011-07-01

    Appetite is a complex process that results from the integration of multiple signals at the hypothalamus. The hypothalamus receives neural signals; hormonal signals such as leptin, cholecystokinin, and ghrelin; and nutrient signals such as glucose, FFA, AA, and VFA. This effect is processed by a specific sequence of neurotransmitters beginning with the arcuate nucleus and orexigenic cells containing neuropeptide Y or agouti-related protein and anorexigenic cells containing proopiomelanocortin (yielding the neurotransmitter α-melanocyte-stimulating hormone) or cells expressing cocaine amphetamine-related transcript. These so-called first-order neurons act on second-order orexigenic neurons (containing either melanin-concentrating hormone or orexin) or act on anorexigenic neurons (e.g., expressing corticotropin-releasing hormone) to alter feed intake. In addition, satiety signals from the liver and gastrointestinal tract signal through the vagus nerve to the nucleus tractus solitarius to cause meal termination, and in combination with the hypothalamus, integrate the various signals to determine the feeding response. The activities of these neuronal pathways are also influenced by numerous factors such as nutrients, fasting, and disease to modify appetite and hence affect growth and reproduction. This review will begin with the central nervous system pathways and then discuss the ways in which hormones and metabolites may alter the process to affect feed intake with emphasis on farm animals.

  9. Selected hormonal and neurotransmitter mechanisms regulating feed intake in sheep.

    Science.gov (United States)

    Sartin, J L; Daniel, J A; Whitlock, B K; Wilborn, R R

    2010-11-01

    Appetite control is a major issue in normal growth and in suboptimal growth performance settings. A number of hormones, in particular leptin, activate or inhibit orexigenic or anorexigenic neurotransmitters within the arcuate nucleus of the hypothalamus, where feed intake regulation is integrated. Examples of appetite regulatory neurotransmitters are the stimulatory neurotransmitters neuropeptide Y (NPY), agouti-related protein (AgRP), orexin and melanin-concentrating hormone and the inhibitory neurotransmitter, melanocyte-stimulating hormone (MSH). Examination of messenger RNA (using in situ hybridization and real-time PCR) and proteins (using immunohistochemistry) for these neurotransmitters in ruminants has indicated that physiological regulation occurs in response to fasting for several of these critical genes and proteins, especially AgRP and NPY. Moreover, intracerebroventricular injection of each of the four stimulatory neurotransmitters can increase feed intake in sheep and may also regulate either growth hormone, luteinizing hormone, cortisol or other hormones. In contrast, both leptin and MSH are inhibitory to feed intake in ruminants. Interestingly, the natural melanocortin-4 receptor (MC4R) antagonist, AgRP, as well as NPY can prevent the inhibition of feed intake after injection of endotoxin (to model disease suppression of appetite). Thus, knowledge of the mechanisms regulating feed intake in the hypothalamus may lead to mechanisms to increase feed intake in normal growing animals and prevent the wasting effects of severe disease in animals.

  10. 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.

  11. Anorexia and impaired glucose metabolism in mice with hypothalamic ablation of Glut4 neurons.

    Science.gov (United States)

    Ren, Hongxia; Lu, Taylor Y; McGraw, Timothy E; Accili, Domenico

    2015-02-01

    The central nervous system (CNS) uses glucose independent of insulin. Nonetheless, insulin receptors and insulin-responsive glucose transporters (Glut4) often colocalize in neurons (Glut4 neurons) in anatomically and functionally distinct areas of the CNS. The apparent heterogeneity of Glut4 neurons has thus far thwarted attempts to understand their function. To answer this question, we used Cre-dependent, diphtheria toxin-mediated cell ablation to selectively remove basal hypothalamic Glut4 neurons and investigate the resulting phenotypes. After Glut4 neuron ablation, mice demonstrate altered hormone and nutrient signaling in the CNS. Accordingly, they exhibit negative energy balance phenotype characterized by reduced food intake and increased energy expenditure, without locomotor deficits or gross neuronal abnormalities. Glut4 neuron ablation affects orexigenic melanin-concentrating hormone neurons but has limited effect on neuropeptide Y/agouti-related protein and proopiomelanocortin neurons. The food intake phenotype can be partially normalized by GABA administration, suggesting that it arises from defective GABAergic transmission. Glut4 neuron-ablated mice show peripheral metabolic defects, including fasting hyperglycemia and glucose intolerance, decreased insulin levels, and elevated hepatic gluconeogenic genes. We conclude that Glut4 neurons integrate hormonal and nutritional cues and mediate CNS actions of insulin on energy balance and peripheral metabolism.

  12. 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.

  13. Análise morfológica e funcional do processo espermatogênico em cobaios (Cavia porcellus da pré-puberdade até a pós-puberdade

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    Amanda K.R. Nunes

    2013-12-01

    Full Text Available Este estudo descreveu as análises morfológica e funcional do processo espermatogênico em cobaios (Cavia porcellus de cinco (S5; seis (S6; nove (S9 e onze (S11 semanas de idade (N=5/grupo. Os aspectos analisados incluíram a contagem das populações celulares presentes no estádio 1 do ciclo do epitélio seminífero (CES, eficiência das mitoses espermatogoniais (RMi, produção meiótica (RMe, rendimento geral da espermatogênese (RGE, índice de células de Sertoli (ICS e capacidade de suporte das células de Sertoli (CSCS. Os resultados mostraram que número médio de espermatogônias A, espermatócitos primários em pré-leptóteno/leptóteno, espermatócitos primários em paquíteno, células espermatogênicas totais e células de Sertoli mostraram variações numéricas em função da idade, entretanto, não detectadas estatisticamente, enquanto espermátides arredondadas aumentaram significativamente na puberdade e depois se estabilizaram. A produção espermatogênica de cobaios de 5 a 11 semanas não atingiu o ponto de estabilização e o RMi, RMe, RGE, ICS e CSCS mostraram variação numérica significativa em função da idade. Os resultados demonstraram que Cavia porcellus na pós-puberdade 2 são um modelo experimental vantajoso para estudos de processos de reconhecimento homólogos, alinhamento, e sinapses durante a prófase meiótica; o rendimento intrínseco da espermatogênese em cobaios é semelhante ao relatado para ratos Wistar, pacas e cutias (Dasyprocta sp. e menor do que em preás, enquanto que a eficiência funcional das células de Sertoli é superior a de cutias e ratos Wistar e inferior à de pacas, rato espinhoso e catetos. Concluiu-se que em cobaios a espermatogênese está completamente estabelecida na semana 6 de idade, indicando a fase púbere do desenvolvimento sexual, e até a semana 11 eles não atingiram a produção espermática diária máxima e, portanto, a maturidade sexual.

  14. Third ventricular coinjection of subthreshold doses of NPY and AgRP stimulate food hoarding and intake and neural activation.

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    Teubner, Brett J W; Keen-Rhinehart, Erin; Bartness, Timothy J

    2012-01-01

    We previously demonstrated that 3rd ventricular (3V) neuropeptide Y (NPY) or agouti-related protein (AgRP) injection potently stimulates food foraging/hoarding/intake in Siberian hamsters. Because NPY and AgRP are highly colocalized in arcuate nucleus neurons in this and other species, we tested whether subthreshold doses of NPY and AgRP coinjected into the 3V stimulates food foraging, hoarding, and intake, and/or neural activation [c-Fos immunoreactivity (c-Fos-ir)] in hamsters housed in a foraging/hoarding apparatus. In the behavioral experiment, each hamster received four 3V treatments by using subthreshold doses of NPY and AgRP for all behaviors: 1) NPY, 2) AgRP, 3) NPY+AgRP, and 4) saline with a 7-day washout period between treatments. Food foraging, intake, and hoarding were measured 1, 2, 4, and 24 h and 2 and 3 days postinjection. Only when NPY and AgRP were coinjected was food intake and hoarding increased. After identical treatment in separate animals, c-Fos-ir was assessed at 90 min and 14 h postinjection, times when food intake (0-1 h) and hoarding (4-24 h) were uniquely stimulated. c-Fos-ir was increased in several hypothalamic nuclei previously shown to be involved in ingestive behaviors and the central nucleus of the amygdala (CeA), but only in NPY+AgRP-treated animals (90 min and 14 h: magno- and parvocellular regions of the hypothalamic paraventricular nucleus and perifornical area; 14 h only: CeA and sub-zona incerta). These results suggest that NPY and AgRP interact to stimulate food hoarding and intake at distinct times, perhaps released as a cocktail naturally with food deprivation to stimulate these behaviors.

  15. Leptin modulates the intrinsic excitability of AgRP/NPY neurons in the arcuate nucleus of the hypothalamus.

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    Baver, Scott B; Hope, Kevin; Guyot, Shannon; Bjørbaek, Christian; Kaczorowski, Catherine; O'Connell, Kristen M S

    2014-04-16

    The hypothalamic arcuate nucleus (ARH) is a brain region critical for regulation of food intake and a primary area for the action of leptin in the CNS. In lean mice, the adipokine leptin inhibits neuropeptide Y (NPY) and agouti-related peptide (AgRP) neuronal activity, resulting in decreased food intake. Here we show that diet-induced obesity in mice is associated with persistent activation of NPY neurons and a failure of leptin to reduce the firing rate or hyperpolarize the resting membrane potential. However, the molecular mechanism whereby diet uncouples leptin's effect on neuronal excitability remains to be fully elucidated. In NPY neurons from lean mice, the Kv channel blocker 4-aminopyridine inhibited leptin-induced changes in input resistance and spike rate. Consistent with this, we found that ARH NPY neurons have a large, leptin-sensitive delayed rectifier K(+) current and that leptin sensitivity of this current is blunted in neurons from diet-induced obese mice. This current is primarily carried by Kv2-containing channels, as the Kv2 channel inhibitor stromatoxin-1 significantly increased the spontaneous firing rate in NPY neurons from lean mice. In HEK cells, leptin induced a significant hyperpolarizing shift in the voltage dependence of Kv2.1 but had no effect on the function of the closely related channel Kv2.2 when these channels were coexpressed with the long isoform of the leptin receptor LepRb. Our results suggest that dynamic modulation of somatic Kv2.1 channels regulates the intrinsic excitability of NPY neurons to modulate the spontaneous activity and the integration of synaptic input onto these neurons in the ARH.

  16. Direct regulation of GnRH neuron excitability by arcuate nucleus POMC and NPY neuron neuropeptides in female mice.

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    Roa, Juan; Herbison, Allan E

    2012-11-01

    Hypothalamic neuropeptide Y (NPY) and proopiomelanocortin (POMC) neurons act to sense and coordinate the brain's responses to metabolic cues. One neuronal network that is very sensitive to metabolic status is that controlling fertility. In this study, we investigated the impact of neuropeptides released by NPY and POMC neurons on the cellular excitability of GnRH neurons, the final output cells of the brain controlling fertility. The majority (∼70%) of GnRH neurons were activated by α-melanocyte-stimulating hormone, and this resulted from the direct postsynaptic activation of melanocortin receptor 3 and melanocortin receptor 4. A small population of GnRH neurons (∼15%) was excited by cocaine and amphetamine-regulated transcript or inhibited by β-endorphin. Agouti-related peptide, released by NPY neurons, was found to have variable inhibitory (∼10%) and stimulatory (∼25%) effects upon subpopulations of GnRH neurons. A variety of NPY and pancreatic polypeptide analogs was used to examine potential NPY interactions with GnRH neurons. Although porcine NPY (Y1/Y2/Y5 agonist) directly inhibited the firing of approximately 45% of GnRH neurons, [Leu(31),Pro(34)]-NPY (Y1/Y4/Y5 agonist) could excite (56%) or inhibit (19%). Experiments with further agonists indicated that Y1 receptors were responsible for suppressing GnRH neuron activity, whereas postsynaptic Y4 receptors were stimulatory. These results show that the activity of GnRH neurons is regulated in a complex manner by neuropeptides released by POMC and NPY neurons. This provides a direct route through which different metabolic cues can regulate fertility.

  17. Seasonal Differences in Relative Gene Expression of Putative Central Appetite Regulators in Arctic Charr (Salvelinus alpinus Do Not Reflect Its Annual Feeding Cycle.

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    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.

  18. 胰高血糖素样肽-1与下丘脑食欲调节%Glucagon-like peptide-1 and appetite regulation in the hypothalamus

    Institute of Scientific and Technical Information of China (English)

    陈瑶; 郗光霞

    2012-01-01

    Hypothalamus is the center of neuroendocrine and appetite-regulation.Glucagons-like peptide-1 (GLP-1) is an incretin which is expressed in the hypothalamus,and regulates the appetite center.GLP-1 is considered as an anorexia-peptide and reduces food intake via negative feedback signal within the hypothalamus.The important pathways of controlling appetite are corticotrophin-releasing hormone ( CRH ),histamine,neuropeptide Y/agouti-related protein ( NPY/AgRP),pro-opiomelanocortin/cocaine and amphetamine regulated transcript (POMC/CART) and AMP-activated protein kinase (AMPK).Research on the mechanism of GLP-1 appetite-regulation may provide evidences on the treatment and prevention of obesity,insulin resistance and type 2 diabetes mellitus.%下丘脑是神经内分泌中枢,也是食欲调节中枢.胰高血糖素样肽-1(GLP-1)是一种胃肠道激素,能够在下丘脑表达并对食欲中枢有调节作用.GLP-1作为一种厌食信号肽,通过促肾上腺皮质激素释放激素(CRH)通路、组胺神经元通路、神经肽和刺鼠相关蛋白(NPY/AgRP)以及前阿片黑皮质素原和可卡因-苯丙胺调节转录肽(POMC/CART)通路及AMP活化蛋白激酶(AMPK)介导的摄食负反馈信号通路参与调节摄食活动.针对GLP-1调节摄食作用机制的研究对肥胖、胰岛素抵抗和2型糖尿病的防治有重要的理论意义.

  19. Glutamate and GABA in appetite regulation

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    Teresa Cardoso Delgado

    2013-08-01

    Full Text Available Appetite is regulated by a coordinated interplay between gut, adipose tissue and brain. A primary site for the regulation of appetite is the hypothalamus where interaction between orexigenic neurons, expressing Neuropeptide Y/Agouti-related protein, and anorexigenic neurons, expressing Pro-opiomelanocortin cocaine/Amphetamine-related transcript, controls energy homeostasis. Within the hypothalamus, several peripheral signals have been shown to modulate the activity of these neurons, including the orexigenic peptide ghrelin and the anorexigenic hormones insulin and leptin. In addition to the accumulated knowledge on neuropeptide signaling, presence and function of amino acid neurotransmitters in key hypothalamic neurons brought a new light into appetite regulation. Therefore, the principal aim of this review will be to describe the current knowledge of the role of amino acid neurotransmitters in the mechanism of neuronal activation during appetite regulation and the associated neuronal-astrocytic metabolic coupling mechanisms.Glutamate and GABA dominate synaptic transmission in the hypothalamus and administration of their receptors agonists into hypothalamic nuclei stimulates feeding. By using 13C High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance spectroscopy based analysis, the Cerdán group has shown that increased neuronal firing in mice hypothalamus, as triggered by appetite during the feeding-fasting paradigm, may stimulate the use of lactate as neuronal fuel leading to increased astrocytic glucose consumption and glycolysis. Moreover, fasted mice showed increased hypothalamic [2-13C]GABA content, which may be explained by the existence of GABAergic neurons in key appetite regulation hypothalamic nuclei. Interestingly, increased [2-13C]GABA concentration in the hypothalamus of fasted animals appears to result mainly from reduction in GABA metabolizing pathways, rather than increased GABA synthesis by augmented activity of the

  20. Maternal and postweaning folic acid supplementation interact to influence body weight, insulin resistance, and food intake regulatory gene expression in rat offspring in a sex-specific manner.

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    Huot, Pedro S P; Ly, Anna; Szeto, Ignatius M Y; Reza-López, Sandra A; Cho, Daniel; Kim, Young-In; Anderson, G Harvey

    2016-04-01

    Maternal intake of multivitamins or folic acid above the basal dietary requirement alters the growth and metabolic trajectory of rat offspring. We hypothesized that a modest increase in the folic acid content of maternal diets would alter the offspring's metabolic phenotype, and that these effects could be corrected by matching the folic acid content of the offspring's diet with that of the maternal diet. Female Sprague-Dawley rats were placed on a control or a 2.5× folic acid-supplemented diet prior to mating and during pregnancy and lactation. At weaning, pups from each maternal diet group were randomized to the control or to the 2.5× folic acid-supplemented diet for 25 weeks. Male pups from dams fed the folic acid-supplemented diet were 3.7% heavier than those from control-fed dams and had lower mRNA expression for leptin receptor Obrb isoform (Lepr) (11%) and Agouti-related protein (Agrp) (14%). In contrast, female pups from folic acid-supplemented dams were 5% lighter than those from control-fed dams and had lower proopiomelanocortin (Pomc) (42%), Lepr (32%), and Agrp (13%), but higher neuropeptide Y (Npy) (18%) mRNA expression. Folic acid supplementation ameliorated the alterations induced by maternal folic acid supplementation in male pups and led to the lowest insulin resistance, but the effects were smaller in female pups and led to the highest insulin resistance. In conclusion, maternal folic acid supplementation at 2.5× the control level was associated with alterations in body weight and hypothalamic gene expression in rat offspring in a sex-specific manner, and some of these effects were attenuated by postweaning folic acid supplementation.

  1. Bitter taste receptors and α-gustducin regulate the secretion of ghrelin with functional effects on food intake and gastric emptying.

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    Janssen, Sara; Laermans, Jorien; Verhulst, Pieter-Jan; Thijs, Theo; Tack, Jan; Depoortere, Inge

    2011-02-01

    Ghrelin is a hunger hormone with gastroprokinetic properties but the factors controlling ghrelin secretion from the stomach are unknown. Bitter taste receptors (T2R) and the gustatory G proteins, α-gustducin (gust) and α-transducin, are expressed in the gut and are involved in the chemosensation of nutrients. This study aimed to investigate whether T2R-agonists affect (i) ghrelin release via α-gustducin and (ii) food intake and gastric emptying via the release of ghrelin. The mouse stomach contains two ghrelin cell populations: cells containing octanoyl and desoctanoyl ghrelin, which were colocalized with α-gustducin and α-transducin, and cells staining for desoctanoyl ghrelin. Gavage of T2R-agonists increased plasma octanoyl ghrelin levels in WT mice but the effect was partially blunted in gust(-/-) mice. Intragastric administration of T2R-agonists increased food intake during the first 30 min in WT but not in gust(-/-) and ghrelin receptor knockout mice. This increase was accompanied by an increase in the mRNA expression of agouti-related peptide in the hypothalamus of WT but not of gust(-/-) mice. The temporary increase in food intake was followed by a prolonged decrease (next 4 h), which correlated with an inhibition of gastric emptying. The delay in emptying, which was partially counteracted by ghrelin, was not mediated by cholecystokinin and GLP-1 but involved a direct inhibitory effect of T2R-agonists on gastric contractility. This study is unique in providing functional evidence that activation of bitter taste receptors stimulates ghrelin secretion. Modulation of endogenous ghrelin levels by tastants may provide novel therapeutic applications for the treatment of weight -and gastrointestinal motility disorders.

  2. Methylprednisolone inhibits IFN-γ and IL-17 expression and production by cells infiltrating central nervous system in experimental autoimmune encephalomyelitis

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    Mostarica-Stojković Marija

    2009-12-01

    Full Text Available Abstract Background Glucocorticoids have been shown to be effective in the treatment of autoimmune diseases of the CNS such as multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE. However, the mechanisms and the site of glucocorticoids' actions are still not completely defined. The aim of this study was to investigate the in vivo effect of the synthetic glucocorticoid methylprednisolone (MP on the expression and production of proinflammatory cytokines interferon (IFN-γ and interleukin (IL-17 by cells infiltrating CNS tissue. Methods Experimental autoimmune encephalomyelitis was induced in Dark Agouti (DA rats by immunization with rat spinal cord homogenate mixed with adjuvants. Commencing on the day when the first EAE signs appeared, DA rats were injected daily for 3 days with MP and/or RU486, an antagonist of glucocorticoid receptor. Cytokine production and gene expression in CNS-infiltrating cells and lymph node cells were measured using ELISA and real time PCR, respectively. Results Treatment of rats with MP ameliorated EAE, and the animals recovered without relapses. Further, MP inhibited IFN-γ and IL-17 expression and production in cells isolated from the CNS of DA rats with EAE after the last injection of MP. The observed effect of MP in vivo treatment was not mediated through depletion of CD4+ T cells among CNS infiltrating cells, or through induction of their apoptosis within the CNS. Finally, the glucocorticoid receptor-antagonist RU486 prevented the inhibitory effect of MP on IFN-γ and IL-17 production both in vitro and in vivo, thus indicating that the observed effects of MP were mediated through glucocorticoid receptor-dependent mechanisms. Conclusion Taken together, these results demonstrate that amelioration of EAE by exogenous glucocorticoids might be, at least partly, ascribed to the limitation of effector cell functions in the target tissue.

  3. Essential role of UCP1 modulating the central effects of thyroid hormones on energy balance

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    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

  4. Investigation of effect of nutritional drink on chemotherapy-induced mucosal injury and tumor growth in an established animal model.

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    Bateman, Emma; Bowen, Joanne; Stringer, Andrea; Mayo, Bronwen; Plews, Erin; Wignall, Anthony; Greenberg, Norman; Schiffrin, Eduardo; Keefe, Dorothy

    2013-09-30

    Chemotherapy-induced mucositis represents a significant burden to quality of life and healthcare costs, and may be improved through enhanced nutritional status. We first determined the safety of two nutritional drinks (plus placebo), and then potential gut protection in tumor-bearing rats in a model of methotrexate-induced mucositis. In study 1, animals were fed one of two test diets (or placebo or control chow pellets) for a total of 60 days and were monitored daily. All diets were found to be safe to administer. In study 2, after seven days of receiving diets, a Dark Agouti Mammary Adenocarcinoma (DAMA) was transplanted subcutaneously. Ten days after starting diets, animals had 2 mg/kg intramuscular methotrexate administered on two consecutive days; after this time, all animals were given soaked chow. Animals were monitored daily for changes in bodyweight, tumor burden and general health. Animals were killed 10, 12 and 16 days after initially starting diets, and tissues were collected at necropsy. In study 1, animals receiving diets had gained 0.8% and 10.8% of their starting bodyweight after 60 days, placebo animals 4.4%, and animals fed on standard chow had gained 15.1%. In study 2, there was no significant influence of test diet on bodyweight, organ weight, tumor burden or biochemical parameters. Only animals treated with MTX exhibited diarrhea, although animals receiving Diet A and Diet C showed a non-significant increase in incidence of diarrhea. Administration of these nutritional drinks did not improve symptoms of mucositis.

  5. Litter size variation in hypothalamic gene expression determines adult metabolic phenotype in Brandt's voles (Lasiopodomys brandtii.

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    Xue-Ying Zhang

    Full Text Available BACKGROUND: Early postnatal environments may have long-term and potentially irreversible consequences on hypothalamic neurons involved in energy homeostasis. Litter size is an important life history trait and negatively correlated with milk intake in small mammals, and thus has been regarded as a naturally varying feature of the early developmental environment. Here we investigated the long-term effects of litter size on metabolic phenotype and hypothalamic neuropeptide mRNA expression involved in the regulation of energy homeostasis, using the offspring reared from large (10-12 and small (3-4 litter sizes, of Brandt's voles (Lasiopodomys brandtii, a rodent species from Inner Mongolia grassland in China. METHODOLOGY/PRINCIPAL FINDINGS: Hypothalamic leptin signaling and neuropeptides were measured by Real-Time PCR. We showed that offspring reared from small litters were heavier at weaning and also in adulthood than offspring from large litters, accompanied by increased food intake during development. There were no significant differences in serum leptin levels or leptin receptor (OB-Rb mRNA in the hypothalamus at weaning or in adulthood, however, hypothalamic suppressor of cytokine signaling 3 (SOCS3 mRNA in adulthood increased in small litters compared to that in large litters. As a result, the agouti-related peptide (AgRP mRNA increased in the offspring from small litters. CONCLUSIONS/SIGNIFICANCE: These findings support our hypothesis that natural litter size has a permanent effect on offspring metabolic phenotype and hypothalamic neuropeptide expression, and suggest central leptin resistance and the resultant increase in AgRP expression may be a fundamental mechanism underlying hyperphagia and the increased risk of overweight in pups of small litters. Thus, we conclude that litter size may be an important and central determinant of metabolic fitness in adulthood.

  6. A sensitive period for environmental regulation of eating behavior and leptin sensitivity.

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    Mainardi, Marco; Scabia, Gaia; Vottari, Teresa; Santini, Ferruccio; Pinchera, Aldo; Maffei, Lamberto; Pizzorusso, Tommaso; Maffei, Margherita

    2010-09-21

    Western lifestyle contributes to body weight dysregulation. Leptin down-regulates food intake by modulating the activity of neural circuits in the hypothalamic arcuate nucleus (ARC), and resistance to this hormone constitutes a permissive condition for obesity. Physical exercise modulates leptin sensitivity in diet-induced obese rats. The role of other lifestyle components in modulating leptin sensitivity remains elusive. Environmentally enriched mice were used to explore the effects of lifestyle change on leptin production/action and other metabolic parameters. We analyzed adult mice exposed to environmental enrichment (EE), which showed decreased leptin, reduced adipose mass, and increased food intake. We also analyzed 50-d-old mice exposed to either EE (YEE) or physical exercise (YW) since birth, both of which showed decreased leptin. YEE mice showed no change in food intake, increased response to leptin administration, increased activation of STAT3 in the ARC. The YW leptin-induced food intake response was intermediate between young mice kept in standard conditions and YEE. YEE exhibited increased and decreased ratios of excitatory/inhibitory synapses onto α-melanocyte-stimulating hormone and agouti-related peptide neurons of the ARC, respectively. We also analyzed animals as described for YEE and then placed in standard cages for 1 mo. They showed no altered leptin production/action but demonstrated changes in excitatory/inhibitory synaptic contacts in the ARC similar to YEE. EE and physical activity resulted in improved insulin sensitivity. In conclusion, EE and physical activity had an impact on feeding behavior, leptin production/action, and insulin sensitivity, and EE affected ARC circuitry. The leptin-hypothalamic axis is maximally enhanced if environmental stimulation is applied during development.

  7. Modulation of orexigenic and anorexigenic peptides gene expression in the rat DVC and hypothalamus by acute immobilization stress

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    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.

  8. Pioglitazone administration alters ovarian gene expression in aging obese lethal yellow mice

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    Weber Mitch

    2008-03-01

    Full Text Available Abstract Background Women with polycystic ovary syndrome (PCOS are often treated with insulin-sensitizing agents, e.g. thiazolidinediones (TZD, which have been shown to reduce androgen levels and improved ovulatory function. Acting via peroxisome proliferator-activated receptor (PPAR gamma, TZD alter the expression of a large variety of genes. Lethal yellow (LY; C57BL/6J Ay/a mice, possessing a mutation (Ay in the agouti gene locus, exhibit progressive obesity, reproductive dysfunction, and altered metabolic regulation similar to women with PCOS. The current study was designed to test the hypothesis that prolonged treatment of aging LY mice with the TZD, pioglitazone, alters the ovarian expression of genes that may impact reproduction. Methods Female LY mice received daily oral doses of either 0.01 mg pioglitazone (n = 4 or an equal volume of vehicle (DMSO; n = 4 for 8 weeks. At the end of treatment, ovaries were removed and DNA microarrays were used to analyze differential gene expression. Results Twenty-seven genes showed at least a two-fold difference in ovarian expression with pioglitazone treatment. These included leptin, angiopoietin, angiopoietin-like 4, Foxa3, PGE1 receptor, resistin-like molecule-alpha (RELM, and actin-related protein 6 homolog (ARP6. For most altered genes, pioglitazone changed levels of expression to those seen in untreated C57BL/6J(a/a non-mutant lean mice. Conclusion TZD administration may influence ovarian function via numerous diverse mechanisms that may or may not be directly related to insulin/IGF signaling.

  9. CARACTERIZACIÓN BROMATOLÓGICA Y MICROBIOLÓGICA DE CARNES PROCEDENTES DE ESPECIES DE ANIMALES REGIONALES DE LA AMAZONIA PERUANA PARA CONSUMO HUMANO

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    Ronald Lozano

    2012-12-01

    Full Text Available La investigación consistió en la caracterización bromatológica y determinación microbiológica de muestras de carnes procedentes de ocho especies de animales silvestres: huangana (Tayassu pecari, majaz o picuro (Agouti paca, sajino (Tayassu tajacu, venado colorado (Mazama americana, tapir (Tapirus terrestris, añuje (Dasyprota fuliginosa, ronsoco (Hydrochaeris hydrochaeris y armadillo (Dasypus novemcinctus; en las localidades de Puerto Belén-Roya-Utucuro, Santa Rosa de Aguaytía, Santa Luz de Abujao, Tacshitea–Sector Parinari en dos ocasiones, ubicadas en las márgenes del río Ucayali y sus afluentes, que fueron analizarlas por la empresa Servicios de Asesoramiento Técnico S.A.C. en Lima.  La caracterización bromatológica indicó que el añuje (Dasyprota fuliginosa mostró el mayor contenido en Proteína cruda seguido de la huangana (Tayassu pecari; en el contenido de grasa destacaron las especies  armadillo (Dasypus novemcinctus y la sachavaca (Tapirus terrestris así también en su contenido calórico.  La especie venado colorado (Mazama americana mostró un mayor valor en cenizas y en carbohidratos la especie huangana (Tayassu pecari.  La determinación microbiológica indicó que todas las muestras presentaron niveles de contaminación dentro de los límites permitidos para aerobios mesófilos viables y niveles de contaminación por coliformes totales, coliformes fecales, algunos muy elevados y también de mohos y levaduras.  Todos presentaron ausencia de Salmonella.

  10. Targeting central melanocortin receptors: a promising novel approach for treating alcohol abuse disorders

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    Jeffrey eOlney

    2014-06-01

    Full Text Available The melanocortin (MC peptides are produced centrally by propiomelanocortin (POMC neurons within the arcuate nucleus of the hypothalamus and act through five seven-transmembrane G-protein coupled melanocortin receptor (MCR subtypes. The MC3R and MC4R subtypes, the most abundant central MCRs, are widely expressed in brain regions known to modulate neurobiological responses to ethanol, including regions of the hypothalamus and extended amygdala. Agouti-related protein (AgRP, also produced in the arcuate nucleus, is secreted in terminals expressing MCRs and functions as an endogenous MCR antagonist. This review highlights recent genetic and pharmacological findings that have implicated roles for the MC and AgRP systems in modulating ethanol consumption. Ethanol consumption is associated with significant alterations in the expression levels of various MC peptides/protein, which suggests that ethanol-induced perturbations of MC/AgRP signaling may modulate excessive ethanol intake. Consistently, MCR agonists decrease, and AgRP increases, ethanol consumption in mice. MCR agonists fail to blunt ethanol intake in mutant mice lacking the MC4R, suggesting that the protective effects of MCR agonists are modulated by the MC4R. Interestingly, recent evidence reveals that MCR agonists are more effective at blunting binge-like ethanol intake in mutant mice lacking the MC3R, suggesting that the MC3R has opposing effects on the MC4R. Finally, mutant mice lacking AgRP exhibit blunted voluntary and binge-like ethanol drinking, consistent with pharmacological studies. Collectively, these preclinical observations provide compelling evidence that compounds that target the MC system may provide therapeutic value for treating alcohol abuse disorders and that the utilization of currently available MC-targeting compounds- such as those being used to treat eating disorders- may be used as effective treatments to this end.

  11. A Novel Analytical Strategy to Identify Fusion Transcripts between Repetitive Elements and Protein Coding-Exons Using RNA-Seq.

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    Tianyuan Wang

    Full Text Available 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.

  12. Preserved energy balance in mice lacking FoxO1 in neurons of Nkx2.1 lineage reveals functional heterogeneity of FoxO1 signaling within the hypothalamus.

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    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.

  13. Micro RNA-155 participates in re-activation of encephalitogenic T cells.

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    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.

  14. Inhibition of myeloid differentiation factor 88 signaling mediated by histidine-grafted poly(β-amino ester ester nanovector induces donor-specific liver allograft tolerance

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    Hu F

    2015-07-01

    Full Text Available Fanguo Hu,1,* Hanjie Wang,2,* Shuangnan Zhang,2 Yao Peng,2 Lin Su,2 Jin Chang,2 Gang Liu11Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 2School of Life Sciences, Tianjin University, Collaborative Innovation Center of Chemical Science and Engineering, Tianjin Engineering Center of Micro-Nano Biomaterials and Detection-Treatment Technology, Tianjin, People’s Republic of China*These authors contributed equally to this workAbstract: Toll-like receptors (TLRs activate biochemical pathways that evoke activation of innate immunity, which leads to dendritic cell maturation and initiation of adaptive immune responses that provoke allograft rejection. We aimed to prolong allograft survival by selectively inhibiting expression of myeloid differentiation factor 88 (MyD88, which is an essential adaptor in TLR signaling. We designed and synthesized a novel histidine-grafted poly(β-amino ester(HGPAE nanovector, which was shown to be safe and efficient both in vitro and in vivo for the delivery of a plasmid containing shRNA targeting MyD88 (pMyD88. We also demonstrated that the pMyD88/HGPAE complex mediated remarkable inhibition of MyD88 expression in rat liver in vivo. We transplanted Dark Agouti rat livers lacking MyD88 as result of transfection with the pMyD88/HGPAE complex into Lewis rats. The recipients survived longer and graft rejection of the donor liver as well as serum levels of IL-2 and IFN-γ in the recipient were significantly reduced.Keywords: immune recognition, allograft rejection, MyD88, short hairpin RNA (shRNA, gene delivery, PAE

  15. Neural and hormonal control of food hoarding.

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    Bartness, Timothy J; Keen-Rhinehart, E; Dailey, M J; Teubner, B J

    2011-09-01

    Many animals hoard food, including humans, but despite its pervasiveness, little is known about the physiological mechanisms underlying this appetitive behavior. We summarize studies of food hoarding in humans and rodents with an emphasis on mechanistic laboratory studies of species where this behavior importantly impacts their energy balance (hamsters), but include laboratory rat studies although their wild counterparts do not hoard food. The photoperiod and cold can affect food hoarding, but food availability is the most significant environmental factor affecting food hoarding. Food-deprived/restricted hamsters and humans exhibit large increases in food hoarding compared with their fed counterparts, both doing so without overeating. Some of the peripheral and central peptides involved in food intake also affect food hoarding, although many have not been tested. Ad libitum-fed hamsters given systemic injections of ghrelin, the peripheral orexigenic hormone that increases with fasting, mimics food deprivation-induced increases in food hoarding. Neuropeptide Y or agouti-related protein, brain peptides stimulated by ghrelin, given centrally to ad libitum-fed hamsters, duplicates the early and prolonged postfood deprivation increases in food hoarding, whereas central melanocortin receptor agonism tends to inhibit food deprivation and ghrelin stimulation of hoarding. Central or peripheral leptin injection or peripheral cholecystokinin-33, known satiety peptides, inhibit food hoarding. Food hoarding markedly increases with pregnancy and lactation. Because fasted and/or obese humans hoard more food in general, and more high-density/high-fat foods specifically, than nonfasted and/or nonobese humans, understanding the mechanisms underlying food hoarding could provide another target for behavioral/pharmacological approaches to curb obesity.

  16. Food intake inhibition in rainbow trout induced by activation of serotonin 5-HT2C receptors is associated with increases in POMC, CART and CRF mRNA abundance in hypothalamus.

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    Pérez-Maceira, Jorge J; Otero-Rodiño, Cristina; Mancebo, María J; Soengas, José L; Aldegunde, Manuel

    2016-04-01

    In rainbow trout, the food intake inhibition induced by serotonin occurs through 5-HT2C and 5-HT1A receptors, though the mechanisms involved are still unknown. Therefore, we assessed if a direct stimulation of 5-HT2C and 5-HT1A serotonin receptors (resulting in decreased food intake in rainbow trout), affects gene expression of neuropeptides involved in the control of food intake, such as pro-opiomelanocortin (POMC), cocaine- and amphetamine-regulated transcript (CART), corticotrophin releasing factor (CRF), and agouti-related peptide (AgRP). In a first set of experiments, the injection of the 5-HT2C receptor agonists MK212 (60 μg kg(-1) icv) and WAY 161503 (1 mg kg(-1) ip), and of the 5-HT1A receptor agonist 8-OH-DPAT (1 mg kg(-1) ip and 30 μg kg(-1) icv) induced food intake inhibition. In a second set of experiments, we observed that the injection of MK212 or WAY 161503 (1 and 3 mg kg(-1)) significantly increased hypothalamic POMC mRNA abundance. CART mRNA abundance in hypothalamus was enhanced by treatment with MK212 and unaffected by WAY 161503. The administration of the 5-HT1A receptor agonist 8-OH-DPAT did not induce any significant variation in the hypothalamic POMC or CART mRNA levels. CRF mRNA abundance was only affected by MK212 that increased hypothalamic values. Finally, hypothalamic AgRP mRNA abundance was only evaluated with the agonist 5-HT2C MK212 resulting in no significant effects. The results show that the reduction in food intake mediated by 5-HT2C receptors is associated with increases in hypothalamic POMC, CART and CRF mRNA abundance.

  17. Methotrexate ameliorates pristane-induced arthritis by decreasing IFN-γ and IL-17A expressions

    Institute of Scientific and Technical Information of China (English)

    Wei-kun HOU; Lie-su MENG; Fang ZHENG; Yu-rong WEN; Wen-hua ZHU; Cong-shan JIANG; Xiao-jing HE; Yan ZHOU; She-min LU

    2011-01-01

    Objective:This study was carried out to test the effects of methotrexate(MTX)and black seed oil(BSO)on pristane-induced arthritis(PIA)in rats.Methods:Inbred dark agouti(DA)rats were induced by a single subcutaneous injection of pristane,and then treated with MTX or BSO.Arthritis severity was evaluated macroscopic,ally and microscopically.Plasma nitric oxide(NO)concentration was determined by the Griess method and cytokine mRNA expression in the spleen was detected by the real-time reverse transcription-polymerase chain reaction(RT-PCR).Results:The clinical arthritis severity was decreased after MTX treatment,while the BSO groups did not show significant changes compared with the disease group.The plasma NO level of the MTX group was significantly decreased compared with the disease group,but the BSO groups showed no difference from the disease group in plasma NO levels.The interferon-γ(IFN-γ)and interleukin-17A(IL-17A)mRNA expressions in the spleens were significantly decreased in the MTX group,but only showed a declining trend in the BSO groups compared with the disease group.Neither MTX nor BSO had an effect on the mRNA expressions of IL-4,transforming growth factor β(TGF-β),and tumor necrosis factor-α(TNF-α)in the spleen.Conclusions:MTX,but not BSO,can reduce the arthritis severity and decrease the mRNA expressions of IFN-γ and IL-17A in pristane-induced arthritis of rats.

  18. Melanocortin receptor 4 deficiency affects body weight regulation, grooming behavior, and substrate preference in the rat.

    Science.gov (United States)

    Mul, Joram D; van Boxtel, Ruben; Bergen, Dylan J M; Brans, Maike A D; Brakkee, Jan H; Toonen, Pim W; Garner, Keith M; Adan, Roger A H; Cuppen, Edwin

    2012-03-01

    Obesity is caused by an imbalance between energy intake and expenditure and has become a major health-care problem in western society. The central melanocortin system plays a crucial role in the regulation of feeding and energy expenditure, and functional loss of melanocortin receptor 4 (MC4R) is the most common genetic cause of human obesity. In this study, we present the first functional Mc4r knockout model in the rat, resulting from an N-ethyl-N-nitrosourea mutagenesis-induced point mutation. In vitro observations revealed impaired membrane-binding and subsequent nonfunctionality of the receptor, whereas in vivo observations showed that functional loss of MC4R increased body weight, food intake, white adipose mass, and changed substrate preference. In addition, intracerebroventricular (ICV) administration of Agouti-Related Protein(79-129) (AgRP(79-129)), an MC4R inverse agonist, or Melanotan-II (MTII), an MC4R agonist, did affect feeding behavior in wild-type rats but not in homozygous mutant rats, confirming complete loss of MC4R function in vivo. Finally, ICV administration of MTII induced excessive grooming behavior in wild-type rats, whereas this effect was absent in homozygous mutant rats, indicating that MTII-induced grooming behavior is exclusively regulated via MC4R pathways. Taken together, we expect that the MC4R rat model described here will be a valuable tool for studying monogenic obesity in humans. More specifically, the relative big size and increased cognitive capacity of rats as compared to mice will facilitate complex behavioral studies and detailed mechanistic studies regarding central function of MC4R, both of which ultimately may help to further understand the specific mechanisms that induce obesity during loss of MC4R function.

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

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    Ishikawa, Akira; Sugiyama, Makoto; Hondo, Eiichi; Kinoshita, Keiji; Yamagishi, Yuki

    2015-01-01

    Oca2(p-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 Oca2(p-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 darkening of the eyes and coat hair with aging. In this study, we developed a novel mouse model showing this unique phenotype. Gross observations revealed that the pink eyes and gray coat hair of the novel mutant young mice became progressively darker in color by approximately 3 months after birth. Light and transmission-electron microscopic observations revealed a marked increase in melanin pigmentation of coat hair shafts and choroid of the eye in the novel mice compared to that in the ordinary mice. Sequence analysis of Oca2(p-cas) revealed a 4.1-kb deletion involving exons 15 and 16 of its wild-type gene. However, there was no sequence difference between the two types of mutant mice. Mating experiments suggested that the novel mutant phenotype was not inherited in a simple fashion, due to incomplete penetrance. The novel spontaneous mutant mouse is the first example of progressive hair darkening animals and is an essential animal model for understanding of the regulation mechanisms of melanin biosynthesis with aging.

  20. Leptin regulates energy intake but fails to facilitate hibernation in fattening Daurian ground squirrels (Spermophilus dauricus).

    Science.gov (United States)

    Xing, Xin; Tang, Gang-Bin; Sun, Ming-Yue; Yu, Chao; Song, Shi-Yi; Liu, Xin-Yu; Yang, Ming; Wang, De-Hua

    2016-04-01

    Body fat storage before hibernation affects the timing of immergence in Daurian ground squirrels (Spermophilus dauricus). Leptin is an adipose signal and plays vital role in energy homeostasis mainly by action in brain. To test the hypothesis that leptin plays a role in facilitating the process of hibernation, squirrels were administrated with recombinant murine leptin (1μg/day) through intracerebroventricular (ICV) injection for 12 days during fattening. From day 7 to 12, animals were moved into a cold room (5±1°C) with constant darkness which functioned as hibernaculum. Energy intake, body mass and core body temperature (Tb) were continuously monitored throughout the course of experiment. Resting metabolic rate (RMR) was measured under both warm and cold conditions. At the end of leptin administration, we measured the serum concentration of hormones related to energy regulation, mRNA expression of hypothalamic neuropeptides and uncoupling protein 1 (UCP1) levels in brown adipose tissue (BAT). Our results showed that during leptin administration, the cumulative food intake and increase of body mass were suppressed while Tb and RMR were unaltered. The proportion of torpid squirrels was not different between two groups. At the end of leptin administration, the expressions of hypothalamic neuropeptide Y and agouti gene-related protein were suppressed. There were no differences in UCP1 mRNA expression or protein content in BAT between groups. Our data suggest that leptin can affect energy intake via hypothalamic neuropeptides, but is not involved in the initiation of hibernation in fattening Daurian ground squirrels.

  1. Leptin Induces Hypertension and Endothelial Dysfunction via Aldosterone-Dependent Mechanisms in Obese Female Mice.

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    Huby, Anne-Cécile; Otvos, Laszlo; Belin de Chantemèle, Eric J

    2016-05-01

    Obesity is a major risk factor for cardiovascular disease in males and females. Whether obesity triggers cardiovascular disease via similar mechanisms in both the sexes is, however, unknown. In males, the adipokine leptin highly contributes to obesity-related cardiovascular disease by increasing sympathetic activity. Females secrete 3× to 4× more leptin than males, but do not exhibit high sympathetic tone with obesity. Nevertheless, females show inappropriately high aldosterone levels that positively correlate with adiposity and blood pressure (BP). We hypothesized that leptin induces hypertension and endothelial dysfunction via aldosterone-dependent mechanisms in females. Leptin control of the cardiovascular function was analyzed in female mice sensitized to leptin via the deletion of protein tyrosine phosphatase 1b (knockout) and in agouti yellow obese hyperleptinemic mice (Ay). Hypersensitivity to leptin (wild-type, 115 ± 2; protein tyrosine phosphatase 1b knockout, 124 ± 2 mm Hg; Pleptin receptor antagonism restored BP and endothelial function in protein tyrosine phosphatase 1b knockout and Ay mice. Hypersensitivity to leptin and obesity reduced BP response to ganglionic blockade in both strains and plasma catecholamine levels in protein tyrosine phosphatase 1b knockout mice. Hypersensitivity to leptin and obesity significantly increased plasma aldosterone levels and adrenal CYP11B2 expression. Chronic leptin receptor antagonism reduced aldosterone levels. Furthermore, chronic leptin and mineralocorticoid receptor blockade reduced BP and improved endothelial function in both leptin-sensitized and obese hyperleptinemic female mice. Together, these data demonstrate that leptin induces hypertension and endothelial dysfunction via aldosterone-dependent mechanisms in female mice and suggest that obesity leads to cardiovascular disease via sex-specific mechanisms.

  2. Increased interleukin-1β levels following low dose MDMA induces tolerance against the 5-HT neurotoxicity produced by challenge MDMA

    Directory of Open Access Journals (Sweden)

    Mayado Andrea

    2011-11-01

    Full Text Available Abstract Background Preconditioning is a phenomenon by which tolerance develops to injury by previous exposure to a stressor of mild severity. Previous studies have shown that single or repeated low dose MDMA can attenuate 5-HT transporter loss produced by a subsequent neurotoxic dose of the drug. We have explored the mechanism of delayed preconditioning by low dose MDMA. Methods Male Dark Agouti rats were given low dose MDMA (3 mg/kg, i.p. 96 h before receiving neurotoxic MDMA (12.5 mg/kg, i.p.. IL-1β and IL1ra levels and 5-HT transporter density in frontal cortex were quantified at 1 h, 3 h or 7 days. IL-1β, IL-1ra and IL-1RI were determined between 3 h and 96 h after low dose MDMA. sIL-1RI combined with low dose MDMA or IL-1β were given 96 h before neurotoxic MDMA and toxicity assessed 7 days later. Results Pretreatment with low dose MDMA attenuated both the 5-HT transporter loss and elevated IL-1β levels induced by neurotoxic MDMA while producing an increase in IL-1ra levels. Low dose MDMA produced an increase in IL-1β at 3 h and in IL-1ra at 96 h. sIL-1RI expression was also increased after low dose MDMA. Coadministration of sIL-1RI (3 μg, i.c.v. prevented the protection against neurotoxic MDMA provided by low dose MDMA. Furthermore, IL-1β (2.5 pg, intracortical given 96 h before neurotoxic MDMA protected against the 5-HT neurotoxicity produced by the drug, thus mimicking preconditioning. Conclusions These results suggest that IL-1β plays an important role in the development of delayed preconditioning by low dose MDMA.

  3. Short-term regulation of the hypothalamic melanocortinergic system under fasting and defined glucose-refeeding conditions in rats: a laser capture microdissection (LMD)-based study.

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    Landmann, Emelie M; Schellong, Karen; Melchior, Kerstin; Rodekamp, Elke; Ziska, Thomas; Harder, Thomas; Plagemann, Andreas

    2012-04-25

    It is well established that under fasting conditions the expression of the orexigenic neuropeptide agouti-related peptide (AGRP) is up-regulated in the hypothalamic arcuate nucleus (ARC), while inconsistent data exist regarding fasting regulation of the anorexigenic neurohormone proopiomelanocortin (POMC). Inconsistencies might have methodological reasons, especially concerning neuromorphological and/or experimental (nutritional) specificity. We analyzed the expression of both neuropeptides in ARC neurons, using lasercapture microdissection (LMD) and real-time PCR in 12h fasted vs. fed Wistar rats as well as after a standardized glucose load, i.e., under clinically relevant conditions in terms of diagnosing glucose intolerance in the human. Under fasting conditions, clear up-regulation of AGRP was observed, with increasing magnitude in ARC single neurons (SNP) as compared to ARC cell layers (+125% vs. +23%, resp.), closely correlated to hypoinsulinemia and hypoleptinemia. Surprisingly, in the fasting state POMC was not found to be down-regulated, neither in ARC cell layers nor in ARC single neurons (+9% vs. +6%). However, glucose-refeeding under diagnostically relevant conditions led to strong neuronal up-regulation of POMC expression in ARC SNP (+128%), and AGRP down-regulation (-50%). In conclusion, experimentally, topographically, and analytically specific and standardized conditions confirmed AGRP in ARC neurons as being neuronally up- and down-regulated, resp., depending on the general nutritional state, while POMC was found to be (up-) regulated only after peripheral glucose load. Findings suggest that POMC in ARC neurons acts glucose-mediated as an "anti-orexigenic" neurohormone, specifically responding to hyperglycemia.

  4. 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, e(r) ) is unknown.

  5. 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.

  6. Oral ingestion of Streptococcus thermophilus does not affect mucositis severity or tumor progression in the tumor-bearing rat.

    Science.gov (United States)

    Tooley, Katie L; Howarth, Gordon S; Lymn, Kerry A; Lawrence, Andrew; Butler, Ross N

    2011-07-15

    Preventative or adjunctive agents for the amelioration of small intestinal chemotherapy-induced mucositis are not currently available for clinical use. We have previously demonstrated that oral ingestion of Streptococcus thermophilus (TH-4) partially attenuated chemotherapy-induced mucositis in the rat. Here we assess the effects of TH-4 on small intestinal damage and tumor progression in tumor-bearing rats with experimentally-induced mucositis. Female Dark Agouti tumor-bearing (mammary adenocarcinoma) rats (n = 36; 139 ± 1 g) had small intestinal damage induced via the administration of methotrexate (MTX). Rats were administered MTX; (1.5 mg/kg intramuscular) or saline at 0 and 24 h; with daily gavage administration of TH-4 (109 cfu/mL) or skim milk from -48 to +96 h post-MTX. Rats were allocated to groups (n=9): saline control, TH-4 control, MTX control or TH-4+MTX. The non-invasive ( 13) C-sucrose breath test (SBT) was conducted prior to tumor inoculation, pre-MTX (-24 h) and prior to sacrifice (96 h) to monitor gut function. At sacrifice small intestinal segments were excised and assessed for sucrase and myeloperoxidase activity as well as histological damage. Irrespective of TH-4 treatment, MTX-treated rats had a significant decrease in bodyweight, SBT levels, sucrase and myeloperoxidase activity, and histological damage score (p 0.05) but failed to alleviate mucositis indices. Although TH-4, at a dose of 109 cfu/mL, yielded neither protection nor amelioration of chemotherapy-induced mucositis, progression of mammary adenocarcinoma was unaffected.

  7. 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.

  8. A study on the mechanisms by which minocycline protects against MDMA ('ecstasy')-induced neurotoxicity of 5-HT cortical neurons.

    Science.gov (United States)

    Orio, Laura; Llopis, Noemi; Torres, Elisa; Izco, Maria; O'Shea, Esther; Colado, M Isabel

    2010-08-01

    3,4-Methylenedioxymethamphetamine (MDMA, 'ecstasy') is a selective 5-HT neurotoxin in rat brain which has been shown to produce acute neuroinflammation characterized by activation of microglia and release of interleukin-1beta (IL-1beta). We aimed to determine whether or not minocycline, a semi-synthetic tetracycline antibiotic capable of inhibiting microglial activation, could prevent the inflammatory response and reduce the toxicity induced by MDMA. Adult male Dark Agouti rats were given minocycline twice a day for 2 days (45 mg/kg on the first day and 90 mg/kg on the second day; 12-h apart, i.p.). MDMA (12.5 mg/kg; i.p.) was given after the third minocycline injection and animals were killed either 1 h later for the determination of NFkappaB binding activity, 3 h later for the determination of IL-1beta, 24 h later for the determination of microglial activation or 7 days later for the determination of [(3)H]-paroxetine binding as a measure of 5-HT neurotoxicity. MDMA increased NFkappaB activation, IL-1beta release and microglial activation both in the frontal cortex and in the hypothalamus and 7 days later produced a reduction in the density of 5-HT uptake sites in both these brain areas. Minocycline prevented the MDMA-induced increase in NFkappaB activation, IL-1beta release and microglial activation in the frontal cortex and prevented the 5-HT neurotoxicity 7 days later. However, in the hypothalamus, in spite of preventing MDMA-induced microglial activation, minocycline failed to prevent MDMA-induced NFkappaB activation, IL-1beta release and neurotoxicity. This suggests that the protective mechanism of minocycline against MDMA-induced neurotoxicity in frontal cortex involves inhibition of MDMA-induced NFkappaB activation possibly through a reduction in IL-1beta signalling.

  9. 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) disrupts blood-brain barrier integrity through a mechanism involving P2X7 receptors.

    Science.gov (United States)

    Rubio-Araiz, Ana; Perez-Hernandez, Mercedes; Urrutia, Andrés; Porcu, Francesca; Borcel, Erika; Gutierrez-Lopez, Maria Dolores; O'Shea, Esther; Colado, Maria Isabel

    2014-08-01

    The recreational drug 3,4-methylenedioxymethamphetamine (MDMA; 'ecstasy') produces a neuro-inflammatory response in rats characterized by an increase in microglial activation and IL-1β levels. The integrity of the blood-brain barrier (BBB) is important in preserving the homeostasis of the brain and has been shown to be affected by neuro-inflammatory processes. We aimed to study the effect of a single dose of MDMA on the activity of metalloproteinases (MMPs), expression of extracellular matrix proteins, BBB leakage and the role of the ionotropic purinergic receptor P2X7 (P2X7R) in the changes induced by the drug. Adult male Dark Agouti rats were treated with MDMA (10 mg/kg, i.p.) and killed at several time-points in order to evaluate MMP-9 and MMP-3 activity in the hippocampus and laminin and collagen-IV expression and IgG extravasation in the dentate gyrus. Microglial activation, P2X7R expression and localization were also determined in the dentate gyrus. Separate groups were treated with MDMA and the P2X7R antagonists Brilliant Blue G (BBG; 50 mg/kg, i.p.) or A-438079 (30 mg/kg, i.p.). MDMA increased MMP-3 and MMP-9 activity, reduced laminin and collagen-IV expression and increased IgG immunoreactivity. In addition, MDMA increased microglial activation and P2X7R immunoreactivity in these cells. BBG suppressed the increase in MMP-9 and MMP-3 activity, prevented basal lamina degradation and IgG extravasation into the brain parenchyma. A-438079 also prevented the MDMA-induced reduction in laminin and collagen-IV immunoreactivity. These results indicate that MDMA alters BBB permeability through an early P2X7R-mediated event, which in turn leads to enhancement of MMP-9 and MMP-3 activity and degradation of extracellular matrix.

  10. Sympathetic Nerve Activity Maintains an Anti-Inflammatory State in Adipose Tissue in Male Mice by Inhibiting TNF-α Gene Expression in Macrophages.

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    Tang, Lijun; Okamoto, Shiki; Shiuchi, Tetsuya; Toda, Chitoku; Takagi, Kazuyo; Sato, Tatsuya; Saito, Kumiko; Yokota, Shigefumi; Minokoshi, Yasuhiko

    2015-10-01

    Adipose tissue macrophages (ATMs) play an important role in the inflammatory response in obese animals. How ATMs are regulated in lean animals has remained elusive, however. We now show that the sympathetic nervous system (SNS) is necessary to maintain the abundance of the mRNA for the proinflammatory cytokine TNF-α at a low level in ATMs of lean mice. Intracerebroventricular injection of agouti-related neuropeptide increased the amount of TNF-α mRNA in epididymal (epi) white adipose tissue (WAT), but not in interscapular brown adipose tissue (BAT), through inhibition of sympathetic nerve activity in epiWAT. The surgical denervation and β-adrenergic antagonist propranolol up-regulated TNF-α mRNA in both epiWAT and BAT in vivo. Signaling by the β2-adrenergic receptor (AR) and protein kinase A down-regulated TNF-α mRNA in epiWAT explants and suppressed lipopolysaccharide-induced up-regulation of TNF-α mRNA in the stromal vascular fraction of this tissue. β-AR-deficient (β-less) mice manifested an increased plasma TNF-α concentration and increased TNF-α mRNA abundance in epiWAT and BAT. TNF-α mRNA abundance was greater in ATMs (CD11b(+) cells of the stromal vascular fraction) from epiWAT or BAT of wild-type mice than in corresponding CD11b(-) cells, and β2-AR mRNA abundance was greater in ATMs than in CD11b(-) cells of epiWAT. Our results show that the SNS and β2-AR-protein kinase A pathway maintain an anti-inflammatory state in ATMs of lean mice in vivo, and that the brain melanocortin pathway plays a role in maintaining this state in WAT of lean mice via the SNS.

  11. Diurnal profiles of hypothalamic energy balance gene expression with photoperiod manipulation in the Siberian hamster, Phodopus sungorus.

    Science.gov (United States)

    Ellis, Claire; Moar, Kim M; Logie, Tracy J; Ross, Alexander W; Morgan, Peter J; Mercer, Julian G

    2008-04-01

    Hypothalamic energy balance genes have been examined in the context of seasonal body weight regulation in the Siberian hamster. Most of these long photoperiod (LD)/short photoperiod (SD) comparisons have been of tissues collected at a single point in the light-dark cycle. We examined the diurnal expression profile of hypothalamic genes in hamsters killed at 3-h intervals throughout the light-dark cycle after housing in LD or SD for 12 wk. Gene expression of neuropeptide Y, agouti-related peptide, proopiomelanocortin, cocaine- and amphetamine-regulated transcript, long-form leptin receptor, suppressor of cytokine signaling-3, melanocortin-3 receptor, melanocortin-4 receptor, and the clock gene Per1 as control were measured by in situ hybridization in hypothalamic nuclei. Effects of photoperiod on gene expression and leptin levels were generally consistent with previous reports. A clear diurnal variation was observed for Per1 in the suprachiasmatic nucleus in both photoperiods. Temporal effects on expression of energy balance genes were restricted to long-form leptin receptor in the arcuate nucleus and ventromedial nucleus, where similar diurnal expression profiles were observed, and melanocortin-4 receptor in the paraventricular nucleus; these effects were only observed in LD hamsters. There was no variation in serum leptin concentration. The 24-h profiles of hypothalamic energy balance gene expression broadly confirm photoperiodic differences that were observed previously, based on single time point comparisons, support the growing consensus that these genes have a limited role in seasonal body weight regulation, and further suggest limited involvement in daily rhythms of food intake.

  12. Blockage of the Neonatal Leptin Surge Affects the Gene Expression of Growth Factors, Glial Proteins, and Neuropeptides Involved in the Control of Metabolism and Reproduction in Peripubertal Male and Female Rats.

    Science.gov (United States)

    Mela, Virginia; Díaz, Francisca; Lopez-Rodriguez, Ana Belen; Vázquez, María Jesús; Gertler, Arieh; Argente, Jesús; Tena-Sempere, Manuel; Viveros, María-Paz; Chowen, Julie A

    2015-07-01

    Leptin (Lep) is important in the development of neuroendocrine circuits involved in metabolic control. Because both Lep and metabolism influence pubertal development, we hypothesized that early changes in Lep signaling could also modulate hypothalamic (HT) systems involved in reproduction. We previously demonstrated that a single injection of a Lep antagonist (Antag) on postnatal day (PND)9, coincident with the neonatal Lep peak, induced sexually dimorphic modifications in trophic factors and markers of cell turnover and neuronal maturation in the HT on PND13. Here, our aim was to investigate whether the alterations induced by Lep antagonism persist into puberty. Accordingly, male and female rats were treated with a pegylated super Lep Antag from PND5 to PND9 and killed just before the normal appearance of external signs of puberty (PND33 in females and PND43 in males). There was no effect on body weight, but in males food intake increased, subcutaneous adipose tissue decreased and HT neuropeptide Y and Agouti-related peptide mRNA levels were reduced, with no effect in females. In both sexes, the Antag increased HT mRNA levels of the kisspeptin receptor, G protein-coupled recepter 54 (Gpr54). Expression of the Lep receptor, trophic factors, and glial markers were differently affected in the HT of peripubertal males and females. Lep production in adipose tissue was decreased in Antag-treated rats of both sexes, with production of other cytokines being differentially regulated between sexes. In conclusion, in addition to the long-term effects on metabolism, changes in neonatal Lep levels modifies factors involved in reproduction that could possibly affect sexual maturation.

  13. Proliferative hypothalamic neurospheres express NPY, AGRP, POMC, CART and Orexin-A and differentiate to functional neurons.

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    Lígia Sousa-Ferreira

    Full Text Available 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 glutamate transporter EAAT3. The orexigenic and anorexigenic phenotype of these neurons was identified by functional response to ghrelin and leptin hormones, respectively. This work demonstrates the presence of appetite-related neuropeptides in hypothalamic progenitor cells and neurons obtained from the differentiation of hypothalamic neurospheres, including the neuronal phenotypes that have been described by others as being affected by hypothalamic neurodegeneration. These in vitro models can be used to study hypothalamic progenitor cells aiming a therapeutic intervention to

  14. [STUDY RELATIVE EXPRESSION OF GENES THAT CONTROL GLUCOSE METABOLISM IN THE LIVER IN MICE WITH DEVELOPMENT OF MELANOCORTIN OBESITY].

    Science.gov (United States)

    Baklanov, A V; Bazhan, N M

    2015-06-01

    The relative gene expressions of glucose-6-phosphatase (G6P), phosphoenolpyruvate carbo- xykinase (PEPCK)--markers of gluconeogenesis, glucokinase (GK)--a marker of glycolysis, glucose transporter type 2 (GLUT2)--a marker of input and output of glucose in the liver were measured during the development of melanocortin (MC) obesity in male mice of C57BL/6J strain with mutation yellow in the Agouti locus (Ay/a mice). The mutation decreases MC receptor activity and induces hyperphagia and MC obesity. The males of the same line with mutation nonagouti were used as control. Tissue samples were taken at age 10 (before obesity), 15 (moderate obesity) and 30 (developed obesity) weeks. It has been shown that Ay/a mice had decreased glucose tolerance since 10-week age. There were age-related changes in mRNA levels in the liver of Ay/a mice, unlike a/a mice. In Ay/a mice the mRNA GLUT2 levels at the age of 10 weeks, mRNA GK levels at the age of 15 weeks, and mRNA G6P levels at the age of 3O weeks were higher than those in Ada mice of other ages. InAYfa mice the mRNA GK levels at the age of 15 weeks and mRNA G6F levels at the age of 30 weeks were increased relatively to those in a/a mice. Thus, Ay/a mice before the development of MK obesity had changes in the mRNA levels genes of proteins that regulate hepatic glucose metabolism, which may contribute to the compensation of glucose metabolism disorders caused by a hereditary decrease of MK system activity

  15. Peptides and Food Intake

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    Carmen Sobrino Crespo

    2014-04-01

    Full Text Available Nutrients created by the digestion of food are proposed to active G protein coupled receptors on the luminal side of enteroendocrine cells e.g. the L-cell. This stimulates the release of gut hormones. Hormones released from the gut and adipose tissue play an important rol in the regulation of food intake and energy expenditure (1.Many circulating signals, including gut hormones, can influence the activity of the arcuate nucleus (ARC neurons directly, after passing across the median eminence. The ARC is adjacent to the median eminence, a circumventricular organ with fenestrated capillaries and hence an incomplete blood-brain barrier (2. The ARC of the hypothalamus is believed to play a crucial role in the regulation of food intake and energy homeostasis. The ARC contains two populations of neurons with opposing effect on food intake (3. Medially located orexigenic neurons (i.e those stimulating appetite express neuropeptide Y (NPY and agouti-related protein (AgRP (4-5. Anorexigenic neurons (i.e. those inhibiting appetite in the lateral ARC express alpha-melanocyte stimulating hormone (α-MSH derived from pro-opiomelanocortin (POMC and cocaine and amphetamine-regulated transcript (CART (6. The balance between activities of these neuronal circuits is critical to body weight regulation.In contrast, other peripheral signals influence the hypothalamus indirectly via afferent neuronal pathway and brainstem circuits. In this context gastrointestinal’s vagal afferents are activated by mechanoreceptors and chemoreceptors, and converge in the nucleus of the tractus solitaries (NTS of the brainstem. Neuronal projections from the NTS, in turn, carry signals to the hypotalamus (1, 7. Gut hormones also alter the activity of the ascending vagal pathway from the gut to the brainstem. In the cases of ghrelin and Peptide tyrosine tyrosine (PYY, there are evidences for both to have a direct action on the arcuate nucleus and an action via the vagus nerve a

  16. 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.

  17. Dysfunction of intraflagellar transport-A causes hyperphagia-induced obesity and metabolic syndrome

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    Damon T. Jacobs

    2016-07-01

    Full Text Available Primary cilia extend from the plasma membrane of most vertebrate cells and mediate signaling pathways. Ciliary dysfunction underlies ciliopathies, which are genetic syndromes that manifest multiple clinical features, including renal cystic disease and obesity. THM1 (also termed TTC21B or IFT139 encodes a component of the intraflagellar transport-A complex and mutations in THM1 have been identified in 5% of individuals with ciliopathies. Consistent with this, deletion of murine Thm1 during late embryonic development results in cystic kidney disease. Here, we report that deletion of murine Thm1 during adulthood results in obesity, diabetes, hypertension and fatty liver disease, with gender differences in susceptibility to weight gain and metabolic dysfunction. Pair-feeding of Thm1 conditional knock-out mice relative to control littermates prevented the obesity and related disorders, indicating that hyperphagia caused the obese phenotype. Thm1 ablation resulted in increased localization of adenylyl cyclase III in primary cilia that were shortened, with bulbous distal tips on neurons of the hypothalamic arcuate nucleus, an integrative center for signals that regulate feeding and activity. In pre-obese Thm1 conditional knock-out mice, expression of anorexogenic pro-opiomelanocortin (Pomc was decreased by 50% in the arcuate nucleus, which likely caused the hyperphagia. Fasting of Thm1 conditional knock-out mice did not alter Pomc nor orexogenic agouti-related neuropeptide (Agrp expression, suggesting impaired sensing of changes in peripheral signals. Together, these data indicate that the Thm1-mutant ciliary defect diminishes sensitivity to feeding signals, which alters appetite regulation and leads to hyperphagia, obesity and metabolic disease.

  18. Dysfunction of intraflagellar transport-A causes hyperphagia-induced obesity and metabolic syndrome.

    Science.gov (United States)

    Jacobs, Damon T; Silva, Luciane M; Allard, Bailey A; Schonfeld, Michael P; Chatterjee, Anindita; Talbott, George C; Beier, David R; Tran, Pamela V

    2016-07-01

    Primary cilia extend from the plasma membrane of most vertebrate cells and mediate signaling pathways. Ciliary dysfunction underlies ciliopathies, which are genetic syndromes that manifest multiple clinical features, including renal cystic disease and obesity. THM1 (also termed TTC21B or IFT139) encodes a component of the intraflagellar transport-A complex and mutations in THM1 have been identified in 5% of individuals with ciliopathies. Consistent with this, deletion of murine Thm1 during late embryonic development results in cystic kidney disease. Here, we report that deletion of murine Thm1 during adulthood results in obesity, diabetes, hypertension and fatty liver disease, with gender differences in susceptibility to weight gain and metabolic dysfunction. Pair-feeding of Thm1 conditional knock-out mice relative to control littermates prevented the obesity and related disorders, indicating that hyperphagia caused the obese phenotype. Thm1 ablation resulted in increased localization of adenylyl cyclase III in primary cilia that were shortened, with bulbous distal tips on neurons of the hypothalamic arcuate nucleus, an integrative center for signals that regulate feeding and activity. In pre-obese Thm1 conditional knock-out mice, expression of anorexogenic pro-opiomelanocortin (Pomc) was decreased by 50% in the arcuate nucleus, which likely caused the hyperphagia. Fasting of Thm1 conditional knock-out mice did not alter Pomc nor orexogenic agouti-related neuropeptide (Agrp) expression, suggesting impaired sensing of changes in peripheral signals. Together, these data indicate that the Thm1-mutant ciliary defect diminishes sensitivity to feeding signals, which alters appetite regulation and leads to hyperphagia, obesity and metabolic disease.

  19. Prey preferences of the jaguar Panthera onca reflect the post-Pleistocene demise of large prey.

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    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.

  20. Redox regulation of apurinic/apyrimidinic endonuclease 1 activity in Long-Evans Cinnamon rats during spontaneous hepatitis.

    Science.gov (United States)

    Karmahapatra, Soumendra Krishna; Saha, Tapas; Adhikari, Sanjay; Woodrick, Jordan; Roy, Rabindra

    2014-03-01

    The Long-Evans Cinnamon (LEC) rat is an animal model for Wilson's disease. This animal is genetically predisposed to copper accumulation in the liver, increased oxidative stress, accumulation of DNA damage, and the spontaneous development of hepatocellular carcinoma. Thus, this animal model is useful for studying the relationship of endogenous DNA damage to spontaneous carcinogenesis. In this study, we have investigated the apurinic/apyrimidinic endonuclease 1 (APE1)-mediated excision repair of endogenous DNA damage, apurinic/apyrimidinic (AP)-sites, which is highly mutagenic and implicated in human cancer. We found that the activity was reduced in the liver extracts from the acute hepatitis period of LEC rats as compared with extracts from the age-matched Long-Evans Agouti rats. The acute hepatitis period had also a heightened oxidative stress condition as assessed by an increase in oxidized glutathione level and loss of enzyme activity of glyceraldehyde 3-phosphate dehydrogenase, a key redox-sensitive protein in cells. Interestingly, the activity reduction was not due to changes in protein expression but apparently by reversible protein oxidation as the addition of reducing agents to extracts of the liver from acute hepatitis period reactivated APE1 activity and thus, confirmed the oxidation-mediated loss of APE1 activity under increased oxidative stress. These findings show for the first time in an animal model that the repair mechanism of AP-sites is impaired by increased oxidative stress in acute hepatitis via redox regulation which contributed to the increased accumulation of mutagenic AP-sites in liver DNA.

  1. Investigation of Effect of Nutritional Drink on Chemotherapy-Induced Mucosal Injury and Tumor Growth in an Established Animal Model

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    Eduardo Schiffrin

    2013-09-01

    Full Text Available Chemotherapy-induced mucositis represents a significant burden to quality of life and healthcare costs, and may be improved through enhanced nutritional status. We first determined the safety of two nutritional drinks (plus placebo, and then potential gut protection in tumor-bearing rats in a model of methotrexate-induced mucositis. In study 1, animals were fed one of two test diets (or placebo or control chow pellets for a total of 60 days and were monitored daily. All diets were found to be safe to administer. In study 2, after seven days of receiving diets, a Dark Agouti Mammary Adenocarcinoma (DAMA was transplanted subcutaneously. Ten days after starting diets, animals had 2 mg/kg intramuscular methotrexate administered on two consecutive days; after this time, all animals were given soaked chow. Animals were monitored daily for changes in bodyweight, tumor burden and general health. Animals were killed 10, 12 and 16 days after initially starting diets, and tissues were collected at necropsy. In study 1, animals receiving diets had gained 0.8% and 10.8% of their starting bodyweight after 60 days, placebo animals 4.4%, and animals fed on standard chow had gained 15.1%. In study 2, there was no significant influence of test diet on bodyweight, organ weight, tumor burden or biochemical parameters. Only animals treated with MTX exhibited diarrhea, although animals receiving Diet A and Diet C showed a non-significant increase in incidence of diarrhea. Administration of these nutritional drinks did not improve symptoms of mucositis.

  2. Molecular evolution of GPCRs: Melanocortin/melanocortin receptors.

    Science.gov (United States)

    Dores, Robert M; Londraville, Richard L; Prokop, Jeremy; Davis, Perry; Dewey, Nathan; Lesinski, Natalie

    2014-06-01

    The melanocortin receptors (MCRs) are a family of G protein-coupled receptors that are activated by melanocortin ligands derived from the proprotein, proopiomelanocortin (POMC). During the radiation of the gnathostomes, the five receptors have become functionally segregated (i.e. melanocortin 1 receptor (MC1R), pigmentation regulation; MC2R, glucocorticoid synthesis; MC3R and MC4R, energy homeostasis; and MC5R, exocrine gland physiology). A focus of this review is the role that ligand selectivity plays in the hypothalamus/pituitary/adrenal-interrenal (HPA-I) axis of teleosts and tetrapods as a result of the exclusive ligand selectivity of MC2R for the ligand ACTH. A second focal point of this review is the roles that the accessory proteins melanocortin 2 receptor accessory protein 1 (MRAP1) and MRAP2 are playing in, respectively, the HPA-I axis (MC2R) and the regulation of energy homeostasis by neurons in the hypothalamus (MC4R) of teleosts and tetrapods. In addition, observations are presented on trends in the ligand selectivity parameters of cartilaginous fish, teleost, and tetrapod MC1R, MC3R, MC4R, and MC5R paralogs, and the modeling of the HFRW motif of ACTH(1-24) when compared with α-MSH. The radiation of the MCRs during the evolution of the gnathostomes provides examples of how the physiology of endocrine and neuronal circuits can be shaped by ligand selectivity, the intersession of reverse agonists (agouti-related peptides (AGRPs)), and interactions with accessory proteins (MRAPs).

  3. Central melanocortins regulate the motivation for sucrose reward.

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    Rahul Pandit

    Full Text Available 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.

  4. Genetic factors control nicotine self-administration in isogenic adolescent rat strains.

    Directory of Open Access Journals (Sweden)

    Hao Chen

    Full Text Available Adult cigarette smokers usually become dependent on cigarettes during adolescence. Despite recent advances in addiction genetics, little data delineates the genetic factors that account for the vulnerability of humans to smoke tobacco. We studied the operant nicotine self-administration (SA behavior of six inbred strains of adolescent male rats (Fisher 344, Brown Norway, Dark Agouti, Spontaneous Hypertensive Rat, Wistar Kyoto and Lewis and six selected F1 hybrids. All rats were trained to press a lever to obtain food starting on postnatal day (PN 32, and then nicotine (0.03 mg/kg/infusion, i.v. reinforcement was made available on PN41-42 (10 consecutive daily 2 h sessions. Of the 12 isogenic strains, Fisher rats self-administered the fewest nicotine infusions (1.45 ± 0.36/d during the last 3 d, while Lewis rats took the most nicotine (13.0 ± 1.4/d. These strains sorted into high, intermediate and low self-administration groups in 2, 2, and 8 strains, respectively. The influence of heredity on nicotine SA (0.64 is similar to that reported for humans. Therefore, this panel of isogenic rat strains effectively models the overall impact of genetics on the vulnerability to acquire nicotine-reinforced behavior during adolescence. Separate groups of rats responded for food starting on PN41. The correlation between nicotine and food reward was not significant. Hence, the genetic control of the motivation to obtain nicotine is distinctly different from food reward, indicating the specificity of the underlying genetic mechanisms. Lastly, the behavior of F1 hybrids was not predicted from the additive behavior of the parental strains, indicating the impact of significant gene-gene interactions on the susceptibility to nicotine reward. Taken together, the behavioral characteristics of this model indicate its strong potential to identify specific genes mediating the human vulnerability to smoke cigarettes.

  5. Regulation of hypothalamic neuropeptides gene expression in diet induced obesity resistant rats: possible targets for obesity prediction?

    Directory of Open Access Journals (Sweden)

    Carlo eCifani

    2015-06-01

    Full Text Available Several factors play a role in obesity (i.e. behavior, environment, and genetics and epigenetic regulation of gene expression has emerged as a potential contributor in the susceptibility and development of obesity. To investigate the individual sensitivity to weight gain/resistance, we here studied gene transcription regulation of several hypothalamic neuropeptides involved in the control of energy balance in rats developing obesity (diet-induced obesity, DIO or not (diet resistant, DR, when fed with a high fat diet. Rats have been followed up to 21 weeks of high fat diet exposure. After 5 weeks high fat diet exposure, the obese phenotype was developed and we observed a selective down-regulation of the orexygenic neuropeptide Y (NPY and peroxisome proliferator-activated receptor gamma (PPAR-γ genes. No changes were observed in the expression of the agouti-related protein (AgRP, as well as for all the anorexigenic genes under study. After long-term high fat diet exposure (21 weeks, NPY and PPAR-γ, as well as most of the genes under study, resulted not be different between DIO and DR, whereas a lower expression of the anorexigenic pro-opio-melanocortin (POMC gene was observed in DIO rats when compared to DR rats. Moreover we observed that changes in NPY and POMC mRNA were inversely correlated with gene promoters DNA methylation. Our findings suggest that selective alterations in hypothalamic peptide genes regulation could contribute to the development of overweight in rats and that environmental factor, as in this animal model, might be partially responsible of these changes via epigenetic mechanism.

  6. Regulation of hypothalamic neuropeptides gene expression in diet induced obesity resistant rats: possible targets for obesity prediction?

    Science.gov (United States)

    Cifani, Carlo; Micioni Di Bonaventura, Maria V; Pucci, Mariangela; Giusepponi, Maria E; Romano, Adele; Di Francesco, Andrea; Maccarrone, Mauro; D'Addario, Claudio

    2015-01-01

    Several factors play a role in obesity (i.e., behavior, environment, and genetics) and epigenetic regulation of gene expression has emerged as a potential contributor in the susceptibility and development of obesity. To investigate the individual sensitivity to weight gain/resistance, we here studied gene transcription regulation of several hypothalamic neuropeptides involved in the control of energy balance in rats developing obesity (diet-induced obesity, DIO) or not (diet resistant, DR), when fed with a high fat diet. Rats have been followed up to 21 weeks of high fat diet exposure. After 5 weeks high fat diet exposure, the obese phenotype was developed and we observed a selective down-regulation of the orexigenic neuropeptide Y (NPY) and peroxisome proliferator-activated receptor gamma (PPAR-γ) genes. No changes were observed in the expression of the agouti-related protein (AgRP), as well as for all the anorexigenic genes under study. After long-term high fat diet exposure (21 weeks), NPY and PPAR-γ, as well as most of the genes under study, resulted not be different between DIO and DR, whereas a lower expression of the anorexigenic pro-opio-melanocortin (POMC) gene was observed in DIO rats when compared to DR rats. Moreover we observed that changes in NPY and POMC mRNA were inversely correlated with gene promoters DNA methylation. Our findings suggest that selective alterations in hypothalamic peptide genes regulation could contribute to the development of overweight in rats and that environmental factor, as in this animal model, might be partially responsible of these changes via epigenetic mechanism.

  7. Effects of dietary fat types on body fatness, leptin, and ARC leptin receptor, NPY, and AgRP mRNA expression.

    Science.gov (United States)

    Wang, Hongqin; Storlien, Len H; Huang, Xu-Feng

    2002-06-01

    Some, but not all, fats are obesogenic. The aim of the present studies was to investigate the effects of changing type and amount of dietary fats on energy balance, fat deposition, leptin, and leptin-related neural peptides: leptin receptor, neuropeptide Y (NPY), agouti-related peptide (AgRP), and proopiomelanocortin (POMC), in C57Bl/6J mice. One week of feeding with a highly saturated fat diet resulted in ~50 and 20% reduction in hypothalamic arcuate NPY and AgRP mRNA levels, respectively, compared with a low-fat or an n-3 or n-6 polyunsaturated high-fat (PUFA) diet without change in energy intake, fat mass, plasma leptin levels, and leptin receptor or POMC mRNA. Similar neuropeptide results were seen at 7 wk, but by then epididymal fat mass and plasma leptin levels were significantly elevated in the saturated fat group compared with low-fat controls. In contrast, fat and leptin levels were reduced in the n-3 PUFA group compared with all other groups. At 7 wk, changing the saturated fat group to n-3 PUFA for 4 wk completely reversed the hyperleptinemia and increased adiposity and neuropeptide changes induced by saturated fat. Changing to a low-fat diet was much less effective. In summary, a highly saturated fat diet induces obesity without hyperphagia. A regulatory reduction in NPY and AgRP mRNA levels is unable to effectively counteract this obesogenic drive. Equally high fat diets emphasizing PUFAs may even protect against obesity.

  8. Hypothalamic neuropeptide expression following chronic food restriction in sedentary and wheel-running rats.

    Science.gov (United States)

    de Rijke, C E; Hillebrand, J J G; Verhagen, L A W; Roeling, T A P; Adan, R A H

    2005-10-01

    When rats are given access to a running-wheel in combination with food restriction, they will become hyperactive and decrease their food intake, a paradoxical phenomenon known as activity-based anorexia (ABA). Little is known about the regulation of the hypothalamic neuropeptides that are involved in the regulation of food intake and energy balance during the development of ABA. Therefore, rats were killed during the development of ABA, before they entered a state of severe starvation. Neuropeptide mRNA expression levels were analysed using quantitative real-time PCR on punches of separate hypothalamic nuclei. As is expected in a state of negative energy balance, expression levels of agouti-related protein (AgRP) and neuropeptide Y (NPY) were increased 5-fold in the arcuate nucleus (ARC) of food-restricted running ABA rats vs 2-fold in sedentary food-restricted controls. The co-regulated expression of AgRP and NPY strongly correlated with relative body weight and white adipose tissue mass. Arcuate expression of pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) was reduced 2-fold in the ABA group. In second-order neurons of the lateral hypothalamic area (LHA), melanin-concentrating hormone (MCH) mRNA expression was upregulated 2-fold in food-restricted running rats, but not in food-restricted sedentary controls. Prepro-orexin, CART and corticotropin-releasing hormone expression levels in the LHA and the paraventricular nucleus (PVN) were unchanged in both food-restricted groups. From this study it was concluded that during the development of ABA, neuropeptides in first-order neurons in the ARC and MCH in the LHA are regulated in an adequate response to negative energy balance, whereas expression levels of the other studied neuropeptides in secondary neurons of the LHA and PVN are unchanged and are probably regulated by factors other than energy status alone.

  9. Regulation of body mass and adiposity in the field vole, Microtus agrestis: a model of leptin resistance.

    Science.gov (United States)

    Król, Elzbieta; Speakman, John R

    2007-02-01

    Adult mammals are typically highly resistant to perturbations in their energy balance. In obese humans, however, this control appears to be lost. Apart from a few exceptional cases, this loss of control occurs despite appropriate levels of circulating leptin -- suggesting that elevated adiposity may be a consequence of failure to respond to the leptin signal: leptin resistance. When cold-acclimated male field voles (Microtus agrestis) are transferred from short (SD, 8 h light) to long (LD, 16 h light) photoperiods, they increase dramatically in body mass and fatness for about 4 weeks. After this period, their mass stabilizes at a new plateau about 25% higher than animals maintained in SD. The increase in adiposity is not caused by significant increases in food intake, but reflects an increase in digestive efficiency. Measures of circulating leptin reveal that the increased adiposity is matched by increased circulating leptin. By infusing voles with exogenous leptin, we have demonstrated that SD voles are leptin sensitive (reducing both body mass and food intake), whereas LD animals are leptin resistant. Voles may therefore be a useful model for understanding the process of leptin resistance. The change in leptin sensitivity in voles was not associated with changes in the levels of gene expression of the orexogenic or anorexogenic neuropeptides, such as neuropeptide Y, agouti-related peptide, POMC and cocaine- and amphetamine-regulated transcript, measured in the hypothalamic arcuate nucleus (ARC). During the phase that body mass was increasing, however, there was a transient increase in the ARC expression of suppressor of cytokine signalling-3 (SOCS3). These data suggest that the changes in the expression of SOCS3 in the ARC may be involved in leptin resistance. However, the mechanism by which these changes may be linked to alterations in digestive efficiency that underpin the changes in adiposity, or how the differences are signalled by changes in photoperiod

  10. Creating leptin-like biofunctions by active immunization against chicken leptin receptor in growing chickens.

    Science.gov (United States)

    Lei, M M; Wu, S Q; Shao, X B; Li, X W; Chen, Z; Ying, S J; Shi, Z D

    2015-01-01

    In this study, immunization against chicken leptin receptor (cLEPR) extracellular domain (ECD) was applied to investigate leptin regulation and LEPR biofunction in growing chicken pullets. A recombinant protein (cLEPR ECD) based on the cLEPR complemenary DNA sequence corresponding to the 582nd to 796th amino acid residues of cLEPR mature peptide was prepared and used as antigen. Immunization against cLEPR ECD in growing chickens increased anti-cLEPR ECD antibody titers in blood, enhanced proportions of phosphorylated janus kinase 2 (JAK2) and served as signal transducer and activator of transcription 3 (STAT3) protein in liver tissue. Chicken live weight gain and abdominal fat mass were significantly decreased (P abdominal fat, and breast muscle (P < 0.05) but decreased fasn expression levels (P < 0.01). Apart from that of lepR, the expression of appetite-regulating genes, such as orexigenic genes, agouti-related peptide (AgRP) and neuropeptide Y (NPY), were upregulated (P < 0.01), whereas the anorexigenic gene proopiomelanocortin (POMC) was downregulated in the hypothalamic tissue of cLEPR-immunized pullets (P < 0.01). Blood concentrations of metabolic molecules, such as glucose, triglycerides, and very-low-density lipoprotein, were significantly decreased in cLEPR-immunized pullets but those of cholesterol, high-density lipoprotein, and low-density lipoprotein increased. These results demonstrate that antibodies to membrane proximal cLEPR ECD enhance cLEPR signal transduction, which stimulates metabolism and reduces fat deposition in chickens.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. Diet-induced obesity causes ghrelin resistance in reward processing tasks.

    Science.gov (United States)

    Lockie, Sarah H; Dinan, Tara; Lawrence, Andrew J; Spencer, Sarah J; Andrews, Zane B

    2015-12-01

    Diet-induced obesity (DIO) causes ghrelin resistance in hypothalamic Agouti-related peptide (AgRP) neurons. However, ghrelin promotes feeding through actions at both the hypothalamus and mesolimbic dopamine reward pathways. Therefore, we hypothesized that DIO would also establish ghrelin resistance in the ventral tegmental area (VTA), a major site of dopaminergic cell bodies important in reward processing. We observed reduced sucrose and saccharin consumption in Ghrelin KO vs Ghrelin WT mice. Moreover, DIO reduced saccharin consumption relative to chow-fed controls. These data suggest that the deletion of ghrelin and high fat diet both cause anhedonia. To assess if these are causally related, we tested whether DIO caused ghrelin resistance in a classic model of drug reward, conditioned place preference (CPP). Chow or high fat diet (HFD) mice were conditioned with ghrelin (1mg/kg in 10ml/kg ip) in the presence or absence of food in the conditioning chamber. We observed a CPP to ghrelin in chow-fed mice but not in HFD-fed mice. HFD-fed mice still showed a CPP for cocaine (20mg/kg), indicating that they maintained the ability to develop conditioned behaviour. The absence of food availability during ghrelin conditioning sessions induced a conditioned place aversion, an effect that was still present in both chow and HFD mice. Bilateral intra-VTA ghrelin injection (0.33μg/μl in 0.5μl) robustly increased feeding in both chow-fed and high fat diet (HFD)-fed mice; however, this was correlated with body weight only in the chow-fed mice. Our results suggest that DIO causes ghrelin resistance albeit not directly in the VTA. We suggest there is impaired ghrelin sensitivity in upstream pathways regulating reward pathways, highlighting a functional role for ghrelin linking appropriate metabolic sensing with reward processing.

  17. Expression of a second ecto-5'-nucleotidase variant besides the usual protein in symptomatic phase of experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Lavrnja, Irena; Laketa, Danijela; Savic, Danijela; Bozic, Iva; Bjelobaba, Ivana; Pekovic, Sanja; Nedeljkovic, Nadezda

    2015-04-01

    Ecto-5'-nucleotidase/cluster of differentiation 73 (CD73) (eN) is a 70-kDa glycoprotein expressed in several different mammalian tissues and cell types. It is the rate-limiting enzyme of the purine catabolic pathway, which catalyzes the hydrolysis of AMP to produce adenosine with known anti-inflammatory and immunosuppressive actions. There is strong evidence for lymphocyte and endothelial cell eN having a role in experimental autoimmune encephalomyelitis (EAE), but the role of eN in cell types within the central nervous system is less clear. We have previously shown that eN activity significantly increased in the lumbar spinal cord during EAE. The present study is aimed to explore molecular pattern of the eN upregulation over the course of the disease and cell type(s) accountable for the induction. EAE was induced in Dark Agouti (DA) rats by immunization with the spinal cord tissue homogenate and adjuvant. Animals were sacrificed 8, 15, and 28 days following immunization (D8, D15, and D28), i.e., at time points which corresponded to the presymptomatic, symptomatic, and postsymptomatic phases of the disease, respectively. Significant increase in eN activity and its upregulation at the gene and the protein levels were demonstrated at D15 and less prominently at D28 in comparison to control. Additionally, reactive astrocytes abundantly present in the lumbar spinal cord parenchyma were identified as principal cell type with significantly elevated eN expression. In all experimental groups, eN was expressed as a 71-kDa protein band of uniform abundance, whereas the overexpression of eN at D15 and D28 was associated with the expression of a second 75-kDa eN variant. The possible outcome of eN upregulation during EAE as a part of protective astrocyte repertoire contributing to the resolution of the disease is discussed.

  18. The orally active melanocortin-4 receptor antagonist BL-6020/979: a promising candidate for the treatment of cancer cachexia.

    Science.gov (United States)

    Dallmann, R; Weyermann, P; Anklin, C; Boroff, M; Bray-French, K; Cardel, B; Courdier-Fruh, I; Deppe, H; Dubach-Powell, J; Erb, M; Haefeli, R H; Henneböhle, M; Herzner, H; Hufschmid, M; Marks, D L; Nordhoff, S; Papp, M; Rummey, C; Santos, G; Schärer, F; Siendt, H; Soeberdt, M; Sumanovski, L T; Terinek, M; Mondadori, C; Güven, N; Feurer, A

    2011-09-01

    BACKGROUND: Under physiological conditions, the melanocortin system is a crucial part of the complex network regulating food intake and energy expenditure. In pathological states, like cachexia, these two parameters are deregulated, i.e., food intake is decreased and energy expenditure is increased-a vicious combination leading to catabolism. Agouti-related protein (AgRP), the endogenous antagonist at the melanocortin-4 receptor (MC-4R), was found to increase food intake and to reduce energy expenditure. This qualifies MC-4R blockade as an attractive mode of action for the treatment of cachexia. Based on this rationale, a novel series of small-molecule MC-4R antagonists was designed, from which the orally active compound BL-6020/979 (formerly known as SNT207979) emerged as the first promising development candidate showing encouraging pre-clinical efficacy and safety properties which are presented here. METHODS AND RESULTS: BL-6020/979 is an orally available, selective and potent MC-4R antagonist with a drug-like profile. It increased food intake and decreased energy expenditure in healthy wild-type but not in MC-4R deficient mice. More importantly, it ameliorated cachexia-like symptoms in the murine C26 adenocarcinoma model; with an effect on body mass and body composition and on the expression of catabolic genes. Moreover, BL-6020/979 showed antidepressant-like properties in the chronic mild stress model in rats and exhibits a favorable safety profile. CONCLUSION: The properties of BL-6020/979 demonstrated in animal models and presented here make it a promising candidate suitable for further development towards a first-in-class treatment option for cachexia that potentially opens up the opportunity to treat two hallmarks of the disease, i.e., decreased food intake and increased energy expenditure, with one drug.

  19. Endotoxemia-induced muscle wasting is associated with the change of hypothalamic neuropeptides in rats.

    Science.gov (United States)

    Duan, Kaipeng; Yu, Wenkui; Lin, Zhiliang; Tan, Shanjun; Bai, Xiaowu; Gao, Tao; Xi, Fengchan; Li, Ning

    2014-12-01

    In critical patients, sepsis-induced muscle wasting is considered to be an important contributor to complications and mortality. Previous work mainly focuses on the peripheral molecular mechanism of muscle degradation, however little evidence exists for the role of central nervous system in the process. In the present study, we, for the first time, characterized the relationship between muscle wasting and central neuropeptide changes in a septic model. Thirty-six adult male Sprague-Dawley rats were intraperitoneally injected with lipopolysaccharide (LPS) or saline. Twelve, 24 and 48 hrs after injection, skeletal muscle and hypothalamus tissues were harvested. Muscle wasting was measured by the mRNA expression of two E3 ubiquitin ligases, muscle ring finger 1 (MuRF-1) and muscle atrophy F-box (MAFbx), as well as 3-methyl-histidine (3-MH) and tyrosine release. Hypothalamic neuropeptides and inflammatory marker expressions were also measured in three time points. LPS injection caused an increase expression of MuRF-1 and MAFbx, and a significant higher release of 3-MH and tyrosine. Hypothalamic neuropeptides, proopiomelanocortin (POMC), cocaine- and amphetamine-regulated transcript (CART), agouti-related protein (AgRP) and neuropeptide Y (NPY) presented a dynamic change after LPS injection. Also, hypothalamic inflammatory markers, interleukin-1 β (IL-1β) and tumor necrosis factor α (TNF-α) increased substantially after LPS administration. Importantly, the expressions of POMC, AgRP and CART were well correlated with muscle atrophy gene, MuRF-1 expression. These findings suggest hypothalamic peptides and inflammation may participate in the sepsis-induced muscle wasting, but the exact mechanism needs further study.

  20. The expression of leptin, hypothalamic neuropeptides and UCP1 before, during and after fattening in the Daurian ground squirrel (Spermophilus dauricus).

    Science.gov (United States)

    Xing, Xin; Yang, Ming; Wang, De-Hua

    2015-06-01

    The Daurian ground squirrel (Spermophilus dauricus) accumulates large amounts of body fat during pre-hibernation fattening. Leptin, an adipose-derived hormone, plays important roles in energy balance and thermogenesis. We predicted that body fat accumulation would lead to the elevation of leptin concentration while its effect on satiety would be suppressed in hypothalamus during fattening. In addition, the uncoupling protein 1 (UCP1) in brown adipose tissue (BAT) would increase and correlated positively with leptin concentration before hibernation. Here, we measured serum leptin concentration and leptin mRNA in white adipose tissue (WAT), hypothalamic neuropeptides involved in energy regulation and UCP1 in BAT before, during and after fattening in squirrels. The fat mass gradually increased during fattening but serum leptin increased mainly in the late phase of fattening, which was consistent with leptin mRNA expression in WAT. During fattening, the mRNA of hypothalamic leptin receptor was up-regulated and correlated positively with serum leptin. Orexigenic neuropeptide Y mRNA increased by 67%; however agouti-related peptide remained unchanged before hibernation. There was no significant change in anorexigenic neuropeptide mRNA. No change in suppressor of cytokine signaling-3 and protein tyrosine phosphatase-1B was detected. UCP1 mRNA expression and protein content in BAT increased significantly after fattening. These changes were independent of environmental conditions and serum leptin concentration. Our results suggest that the dissociation of leptin production and adiposity during fattening may facilitate fat accumulation. No evidence of suppressed leptin signal was found in fattening squirrels. The UCP1 recruitment in post-fattening squirrels could occur without winter-like acclimation and increased leptin.

  1. Glucocorticoids are required for meal-induced changes in the expression of hypothalamic neuropeptides.

    Science.gov (United States)

    Uchoa, Ernane Torres; Silva, Lilian Eslaine C M; de Castro, Margaret; Antunes-Rodrigues, Jose; Elias, Lucila L K

    2012-06-01

    Glucocorticoid deficiency is associated with a decrease of food intake. Orexigenic peptides, neuropeptide Y (NPY) and agouti related protein (AgRP), and the anorexigenic peptide proopiomelanocortin (POMC), expressed in the arcuate nucleus of the hypothalamus (ARC), are regulated by meal-induced signals. Orexigenic neuropeptides, melanin-concentrating hormone (MCH) and orexin, expressed in the lateral hypothalamic area (LHA), also control food intake. Thus, the present study was designed to test the hypothesis that glucocorticoids are required for changes in the expression of hypothalamic neuropeptides induced by feeding. Male Wistar rats (230-280 g) were subjected to ADX or sham surgery. ADX animals received 0.9% NaCl in the drinking water, and half of them received corticosterone in the drinking water (B: 25 mg/L, ADX+B). Six days after surgery, animals were fasted for 16 h and they were decapitated before or 2 h after refeeding for brain tissue and blood collections. Adrenalectomy decreased NPY/AgRP and POMC expression in the ARC in fasted and refed animals, respectively. Refeeding decreased NPY/AgRP and increased POMC mRNA expression in the ARC of sham and ADX+B groups, with no effects in ADX animals. The expression of MCH and orexin mRNA expression in the LHA was increased in ADX and ADX+B groups in fasted condition, however there was no effect of refeeding on the expression of MCH and orexin in the LHA in the three experimental groups. Refeeding increased plasma leptin and insulin levels in sham and ADX+B animals, with no changes in leptin concentrations in ADX group, and insulin response to feeding was lower in this group. Taken together, these data demonstrated that circulating glucocorticoids are required for meal-induced changes in NPY, AgRP and POMC mRNA expression in the ARC. The lower leptin and insulin responses to feeding may contribute to the altered hypothalamic neuropeptide expression after adrenalectomy.

  2. Role of neuropeptides in appetite regulation and obesity--a review.

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    Arora, Sarika; Anubhuti

    2006-12-01

    Obesity represents the most prevalent nutritional problem worldwide which in the long run predisposes to development of diabetes mellitus, hypertension, endometrial carcinoma, osteoarthritis, gall stones and cardiovascular diseases. Despite significant reductions in dietary fat consumption, the prevalence of obesity is on a rise and is taking on pandemic proportions. Obesity develops when energy intake exceeds energy expenditure over time. Recently, a close evolutionary relationship between the peripheral and hypothalamic neuropeptides has become apparent. The hypothalamus being the central feeding organ mediates regulation of short-term and long-term dietary intake via synthesis of various orexigenic and anorectic neuropeptides. The structure and function of many hypothalamic peptides (neuropeptide Y (NPY), melanocortins, agouti-related peptide (AGRP), cocaine and amphetamine regulated transcript (CART), melanin concentrating hormone (MCH), orexins have been characterized in rodent models The peripheral neuropeptides such as cholecystokinin (CCK), ghrelin, peptide YY (PYY3-36), amylin, bombesin regulate important gastrointestinal functions such as motility, secretion, absorption, provide feedback to the central nervous system on availability of nutrients and may play a part in regulating food intake. The pharmacological potential of several endogenous peripheral peptides released prior to, during and/or after feeding are being explored. Long-term regulation is provided by the main circulating hormones leptin and insulin. These systems implicated in hypothalamic appetite regulation provide potential targets for treatment of obesity which could potentially pass into clinical development in the next 5 years. This review summarizes various effects and interrelationship of these central and peripheral neuropeptides in metabolism, obesity and their potential role as targets for treatment of obesity.

  3. Differential effect of prolonged food restriction and fasting on hypothalamic malonyl-CoA concentration and expression of orexigenic and anorexigenic neuropeptides genes in rats.

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    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.

  4. Abrogation of the immunosuppressive effect of donor spleen cells on renal allografts in the rat by irradiation or heat treatment

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    Cranston, D.; Wood, K.J.; Morris, P.J.

    1986-09-01

    In the donor-recipient strain combination Lewis (RT1l) to Dark Agouti (RT1a), indefinite renal allograft survival (MST greater than 100 days) was induced by pretreating recipient animals i.v. with 10(6) to 10(8) viable spleen lymphocytes, seven days before transplantation. Pretreatment with 10(4) or 10(5) cells was ineffective (MST 10 days). However when 10(7) live, but heat-treated (55 degrees C for 10 min) or irradiated (1000 rads) cells were used, all the animals rejected the allograft in a normal fashion (MST 10 and 11 days, respectively). Median survival time of third-party controls was 10 days. The relative amount of cell surface major histocompatibility antigens (class I and class II) expressed by the three spleen cell preparations was investigated using monoclonal antibodies and fluorescence activated cell sorter analysis and found to be similar. After 24 hr in culture, only 1% of heat-treated and 10% of irradiated cells were viable, in contrast to 75% of untreated splenocytes. Trafficking of these lymphocytes in recipient animals was investigated by 51chromium labeling of the cells: 30% of lymphocytes had localized in the liver within 3 hr with little difference in localization among the different cell preparations. But, although 20% of normal and irradiated cells localized in the spleen within 3 hr, at no stage were more than 5% of the heat-treated cells found in the spleen. It is suggested that the length of time viable donor lymphocytes remain in the recipient circulation is important in the induction of specific immunosuppression by spleen lymphocytes.

  5. Development of chronic allograft rejection and arterial hypertension in Brown Norway rats after renal transplantation.

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    Vaskonen, T; Mervaala, E; Nevala, R; Soots, A; Krogerus, L; Lähteenmäki, T; Karppanen, H; Vapaatalo, H; Ahonen, J

    2000-01-01

    The cardiovascular and renal pathophysiology associated with chronic renal allograft rejection under triple drug immunosuppressive treatment was studied using a recently developed model (Brown Norway (BN) rats) in a 6-week experiment. Renal transplantation was performed to 10-week-old rats in a rat strain combination of Dark Agouti (DA) --> BN. The right kidney was removed from another group of BN rats (uninephrectomized). A triple drug treatment comprising cyclosporine (10 mg/kg subcutaneously, s.c.), azathioprine (2 mg/kg s.c.) and methylprednisolone (1.6 mg/kg s.c.) was given to each rat daily for 6 weeks. A control group underwent no operations nor drug treatment. After the transplantation, the systolic blood pressure in this group was increased from 116 +/- 2 to 166 +/- 2 mmHg, while in the uninephrectomized group the rise was from 115 +/- 4 to 146 +/- 4 mmHg, and no change was observed in the blood pressures of the control group. The vascular relaxation responses of mesenteric arterial rings in vitro to acetylcholine were inhibited in both the transplantation group and the uninephrectomized group as compared with the control group, but few significant differences were found in the contraction responses to noradrenaline and potassium chloride. Graft histology was examined after 6 weeks, quantified by using the chronic allograft damage index (CADI). Changes specific to a chronic rejection reaction were observed in the allografts (CADI mean 6.0) but no injuries were seen in the rats' own kidneys (CADI mean 1.2). Our findings show that allograft rejection in BN rats after renal transplantation is associated with the development of arterial hypertension. The combination of cyclosporine, methylprednisolone and azathioprine also rises blood pressure in uninephrectomized BN rats. The hypertensive effects of the drug treatment and graft rejection are associated with endothelial dysfunction.

  6. Impact of hypothalamic reactive oxygen species in the control of energy metabolism and food intake

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    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.

  7. The local effect of octreotide on mechanical pain sensitivity is more sensitive in DA rats than DA.1U rats.

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    Yao, Fan-Rong; Wang, Hui-Sheng; Guo, Yuan; Zhao, Yan

    2016-02-01

    A recent study by the authors indicated that major histocompatibility complex (MHC) genes are associated with the differences in basal pain sensitivity and in formalin model between Dark-Agouti (DA) and novel congenic DA.1U rats, which have the same genetic background as DA rats except for the u alleles of MHC. The objective of the present study is to investigate whether there is a difference in the pristane-induced arthritis (PIA) model and local analgesic effect of octreotide (OCT) between DA and DA.1U rats. The hindpaw mechanical withdrawal threshold (MWT) and heat withdrawal latency (HWL) were observed. The C unit firings of the tibial nerve evoked by non-noxious and noxious toe movements were recorded by electrophysiological methods in normal and PIA models in DA and DA.1U rats before and after local OCT administration. The expression of somatostatin receptor 2A (SSTR2A) was observed by immunohistochemistry. The results demonstrate that DA rats have a higher mechanical sensitivity than DA.1U rats after PIA. Local OCT administration significantly elevated MWT in DA rats under normal and PIA sate, but not in DA.1U rats. The electrophysiological experiments showed OCT significantly attenuated the firings of C units evoked by non-noxious and noxious stimulation in DA rats more than those in DA.1U rats both in normal and PIA states. In addition, the expression of SSTR2A in the dorsal horn of the spinal cord was significantly higher in DA than in DA.1U rats. All of the findings suggest a higher local analgesic effect of OCT in DA rats than DA.1U rats, which might be associated with the MHC genes.

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

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    Melissa K Friswell

    Full Text Available BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSION/SIGNIFICANCE: 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.

  9. Monoaminergic and neuropeptidergic neurons have distinct expression profiles of histone deacetylases.

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    Kenkichi Takase

    Full Text Available Monoaminergic and neuropeptidergic neurons regulate a wide variety of behaviors, such as feeding, sleep/wakefulness behavior, stress response, addiction, and social behavior. These neurons form neural circuits to integrate different modalities of behavioral and environmental factors, such as stress, maternal care, and feeding conditions. One possible mechanism for integrating environmental factors through the monoaminergic and neuropeptidergic neurons is through the epigenetic regulation of gene expression via altered acetylation of histones. Histone deacetylases (HDACs play an important role in altering behavior in response to environmental factors. Despite increasing attention and the versatile roles of HDACs in a variety of brain functions and disorders, no reports have detailed the localization of the HDACs in the monoaminergic and neuropeptidergic neurons. Here, we examined the expression profile of the HDAC protein family from HDAC1 to HDAC11 in corticotropin-releasing hormone, oxytocin, vasopressin, agouti-related peptide (AgRP, pro-opiomelanocortin (POMC, orexin, histamine, dopamine, serotonin, and noradrenaline neurons. Immunoreactivities for HDAC1,-2,-3,-5,-6,-7,-9, and -11 were very similar among the monoaminergic and neuropeptidergic neurons, while the HDAC4, -8, and -10 immunoreactivities were clearly different among neuronal groups. HDAC10 expression was found in AgRP neurons, POMC neurons, dopamine neurons and noradrenaline neurons but not in other neuronal groups. HDAC8 immunoreactivity was detected in the cytoplasm of almost all histamine neurons with a pericellular pattern but not in other neuropeptidergic and monoaminergic neurons. Thus, the differential expression of HDACs in monoaminergic and neuropeptidergic neurons may be crucial for the maintenance of biological characteristics and may be altered in response to environmental factors.

  10. Evidence suggesting phosphodiesterase-3B regulation of NPY/AgRP gene expression in mHypoE-46 hypothalamic neurons.

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    Anamthathmakula, Prashanth; Sahu, Maitrayee; Sahu, Abhiram

    2015-09-14

    Hypothalamic neurons expressing neuropeptide Y (NPY) and agouti related-protein (AgRP) are critical regulators of feeding behavior and body weight, and transduce the action of many peripheral signals including leptin and insulin. However, intracellular signaling molecules involved in regulating NPY/AgRP neuronal activity are incompletely understood. Since phosphodiesterase-3B (PDE3B) mediates the hypothalamic action of leptin and insulin on feeding, and is expressed in NPY/AgRP neurons, PDE3B could play a significant role in regulating NPY/AgRP neuronal activity. To investigate the direct regulation of NPY/AgRP neuronal activity by PDE3B, we examined the effects of gain-of-function or reduced function of PDE3B on NPY/AgRP gene expression in a clonal hypothalamic neuronal cell line, mHypoE-46, which endogenously express NPY, AgRP and PDE3B. Overexpression of PDE3B in mHypoE-46 cells with transfection of pcDNA-3.1-PDE3B expression plasmid significantly decreased NPY and AgRP mRNA levels and p-CREB levels as compared to the control plasmid. For the PDE3B knockdown study, mHypoE-46 cells transfected with lentiviral PDE3BshRNAmir plasmid or non-silencing lentiviral shRNAmir control plasmid were selected with puromycin, and stably transfected cells were grown in culture for 48h. Results showed that PDE3BshRNAmir mediated knockdown of PDE3B mRNA and protein levels (∼60-70%) caused an increase in both NPY and AgRP gene expression and in p-CREB levels. Together, these results demonstrate a reciprocal change in NPY and AgRP gene expression following overexpression and knockdown of PDE3B, and suggest a significant role for PDE3B in the regulation of NPY/AgRP gene expression in mHypoE-46 hypothalamic neurons.

  11. Missense and nonsense mutations in melanocortin 1 receptor (MC1R gene of different goat breeds: association with red and black coat colour phenotypes but with unexpected evidences

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    Davoli Roberta

    2009-08-01

    Full Text Available Abstract Background Agouti and Extension loci control the relative amount of eumelanin and pheomelanin production in melanocytes that, in turn, affects pigmentation of skin and hair. The Extension locus encodes the melanocortin 1 receptor (MC1R whose permanent activation, caused by functional mutations, results in black coat colour, whereas other inactivating mutations cause red coat colour in different mammals. Results The whole coding region of the MC1R gene was sequenced in goats of six different breeds showing different coat colours (Girgentana, white cream with usually small red spots in the face; Maltese, white with black cheeks and ears; Derivata di Siria, solid red; Murciano-Granadina, solid black or solid brown; Camosciata delle Alpi, brown with black stripes; Saanen, white; F1 goats and the parental animals. Five single nucleotide polymorphisms (SNPs were identified: one nonsense mutation (p.Q225X, three missense mutations (p.A81V, p.F250V, and p.C267W, and one silent mutation. The stop codon at position 225 should cause the production of a shorter MC1R protein whose functionality may be altered. These SNPs were investigated in a larger sample of animals belonging to the six breeds. The Girgentana breed was almost fixed for the p.225X allele. However, there was not complete association between the presence of red spots in the face and the presence of this allele in homozygous condition. The same allele was identified in the Derivata di Siria breed. However, its frequency was only 33%, despite the fact that these animals are completely red. The p.267W allele was present in all Murciano-Granadina black goats, whereas it was never identified in the brown ones. Moreover, the same substitution was present in almost all Maltese goats providing evidence of association between this mutation and black coat colour. Conclusion According to the results obtained in the investigated goat breeds, MC1R mutations may determine eumelanic and pheomelanic

  12. Alterations in the hypothalamic melanocortin pathway in amyotrophic lateral sclerosis.

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    Vercruysse, Pauline; Sinniger, Jérôme; El Oussini, Hajer; Scekic-Zahirovic, Jelena; Dieterlé, Stéphane; Dengler, Reinhard; Meyer, Thomas; Zierz, Stephan; Kassubek, Jan; Fischer, Wilhelm; Dreyhaupt, Jens; Grehl, Torsten; Hermann, Andreas; Grosskreutz, Julian; Witting, Anke; Van Den Bosch, Ludo; Spreux-Varoquaux, Odile; Ludolph, Albert C; Dupuis, Luc

    2016-04-01

    Amyotrophic lateral sclerosis, the most common adult-onset motor neuron disease, leads to death within 3 to 5 years after onset. Beyond progressive motor impairment, patients with amyotrophic lateral sclerosis suffer from major defects in energy metabolism, such as weight loss, which are well correlated with survival. Indeed, nutritional intervention targeting weight loss might improve survival of patients. However, the neural mechanisms underlying metabolic impairment in patients with amyotrophic lateral sclerosis remain elusive, in particular due to the lack of longitudinal studies. Here we took advantage of samples collected during the clinical trial of pioglitazone (GERP-ALS), and characterized longitudinally energy metabolism of patients with amyotrophic lateral sclerosis in response to pioglitazone, a drug with well-characterized metabolic effects. As expected, pioglitazone decreased glycaemia, decreased liver enzymes and increased circulating adiponectin in patients with amyotrophic lateral sclerosis, showing its efficacy in the periphery. However, pioglitazone did not increase body weight of patients with amyotrophic lateral sclerosis independently of bulbar involvement. As pioglitazone increases body weight through a direct inhibition of the hypothalamic melanocortin system, we studied hypothalamic neurons producing proopiomelanocortin (POMC) and the endogenous melanocortin inhibitor agouti-related peptide (AGRP), in mice expressing amyotrophic lateral sclerosis-linked mutant SOD1(G86R). We observed lower Pomc but higher Agrp mRNA levels in the hypothalamus of presymptomatic SOD1(G86R) mice. Consistently, numbers of POMC-positive neurons were decreased, whereas AGRP fibre density was elevated in the hypothalamic arcuate nucleus of SOD1(G86R) mice. Consistent with a defect in the hypothalamic melanocortin system, food intake after short term fasting was increased in SOD1(G86R) mice. Importantly, these findings were replicated in two other amyotrophic

  13. MC1R and the response of melanocytes to ultraviolet radiation

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    Rouzaud, Francois [Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Building 37, Room 2132, Bethesda, MD 20892 (United States); Kadekaro, Ana Luisa [Department of Dermatology, University of Cincinnati, College of Medicine, Cincinnati, OH 45267 (United States); Abdel-Malek, Zalfa A. [Department of Dermatology, University of Cincinnati, College of Medicine, Cincinnati, OH 45267 (United States); Hearing, Vincent J. [Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Building 37, Room 2132, Bethesda, MD 20892 (United States)]. E-mail: hearingv@nih.gov

    2005-04-01

    The constitutive color of our skin plays a dramatic role in our photoprotection from solar ultraviolet radiation (UVR) that reaches the Earth and in minimizing DNA damage that gives rise to skin cancer. More than 120 genes have been identified and shown to regulate pigmentation, one of the key genes being melanocortin 1 receptor (MC1R) that encodes the melanocortin 1 receptor (MC1R), a seven-transmembrane G protein-coupled receptor expressed on the surface of melanocytes. Modulation of MC1R function regulates melanin synthesis by melanocytes qualitatively and quantitatively. The MC1R is regulated by the physiological agonists {alpha}-melanocyte-stimulating hormone ({alpha}MSH) and adrenocorticotropic hormone (ACTH), and antagonist agouti signaling protein (ASP). Activation of the MC1R by binding of an agonist stimulates the synthesis of eumelanin primarily via activation of adenylate cyclase. The significance of cutaneous pigmentation lies in the photoprotective effect of melanin, particularly eumelanin, against sun-induced carcinogenesis. Epidermal melanocytes and keratinocytes respond to UVR by increasing their expression of {alpha}MSH and ACTH, which up-regulate the expression of MC1R, and consequently enhance the response of melanocytes to melanocortins. Constitutive skin pigmentation dramatically affects the incidence of skin cancer. The pigmentary phenotype characterized by red hair, fair complexion, inability to tan and tendency to freckle is an independent risk factor for all skin cancers, including melanoma. The MC1R gene is highly polymorphic in human populations, and allelic variation at this locus accounts, to a large extent, for the variation in pigmentary phenotypes and skin phototypes (SPT) in humans. Several allelic variants of the MC1R gene are associated with the red hair and fair skin (RHC) phenotype, and carrying one of these variants is thought to diminish the ability of the epidermis to respond to DNA damage elicited by UVR. The MC1R gene is

  14. A composite six bp in-frame deletion in the melanocortin 1 receptor (MC1R gene is associated with the Japanese brindling coat colour in rabbits (Oryctolagus cuniculus

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    Russo Vincenzo

    2010-07-01

    Full Text Available Abstract Background In the domestic rabbit (Oryctolagus cuniculus, classical genetic studies have identified five alleles at the Extension locus: ED (dominant black, ES (steel, weaker version of ED, E (wild type, normal extension of black, eJ(Japanese brindling, mosaic distribution of black and yellow and e (non-extension of black, yellow/red with white belly. Sequencing almost the complete coding sequence (CDS of the rabbit MC1R gene, we recently identified two in-frame deletions associated with dominant black (c.280_285del6; alleles ED or ES and recessive red (c.304_333del30; allele e coat colours. It remained to characterize the eJallele whose phenotypic effect is similar to the Orange and Sex-linked yellow loci of cat and Syrian hamster. Results We sequenced the whole CDS in 25 rabbits of different coat colours including 10 Japanese and 10 Rhinelander (tricolour rabbits and identified another 6 bp-in frame deletion flanked by a G > A transition in 5' (c.[124G>A;125_130del6] that was present in all animals with Japanese brindling coat colour and pattern. These mutations eliminate two amino acids in the first transmembrane domain and, in addition, cause an amino acid substitution at position 44 of the wild type sequence. Genotyping 371 rabbits of 31 breeds with different coat colour this allele (eJ was present in homozygous state in Japanese, Rhinelander and Dutch tricolour rabbits only (except one albino rabbit. Rabbits with eJ/eJ genotype were non fixed at the non-agouti mutation we previously identified in the ASIP gene. Segregation in F1 and F2 families confirmed the order of dominance already determined by classical genetic experiments with a possible dose effect evident comparing eJ/eJ and eJ/e animals. MC1R mRNA was expressed in black hair skin regions only. Conclusions The c.[124A;125_130del6] allele may be responsible for a MC1R variant determining eumelanin production in the black areas. However, the mechanism determining the

  15. Engineering agatoxin, a cystine-knot peptide from spider venom, as a molecular probe for in vivo tumor imaging.

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    Sarah J Moore

    Full Text Available BACKGROUND: Cystine-knot miniproteins, also known as knottins, have shown great potential as molecular scaffolds for the development of targeted therapeutics and diagnostic agents. For this purpose, previous protein engineering efforts have focused on knottins based on the Ecballium elaterium trypsin inhibitor (EETI from squash seeds, the Agouti-related protein (AgRP neuropeptide from mammals, or the Kalata B1 uterotonic peptide from plants. Here, we demonstrate that Agatoxin (AgTx, an ion channel inhibitor found in spider venom, can be used as a molecular scaffold to engineer knottins that bind with high-affinity to a tumor-associated integrin receptor. METHODOLOGY/PRINCIPAL FINDINGS: We used a rational loop-grafting approach to engineer AgTx variants that bound to αvβ3 integrin with affinities in the low nM range. We showed that a disulfide-constrained loop from AgRP, a structurally-related knottin, can be substituted into AgTx to confer its high affinity binding properties. In parallel, we identified amino acid mutations required for efficient in vitro folding of engineered integrin-binding AgTx variants. Molecular imaging was used to evaluate in vivo tumor targeting and biodistribution of an engineered AgTx knottin compared to integrin-binding knottins based on AgRP and EETI. Knottin peptides were chemically synthesized and conjugated to a near-infrared fluorescent dye. Integrin-binding AgTx, AgRP, and EETI knottins all generated high tumor imaging contrast in U87MG glioblastoma xenograft models. Interestingly, EETI-based knottins generated significantly lower non-specific kidney imaging signals compared to AgTx and AgRP-based knottins. CONCLUSIONS/SIGNIFICANCE: In this study, we demonstrate that AgTx, a knottin from spider venom, can be engineered to bind with high affinity to a tumor-associated receptor target. This work validates AgTx as a viable molecular scaffold for protein engineering, and further demonstrates the promise of using

  16. Imprinted genes and transpositions: epigenomic targets for low dose radiation effects. Final report

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    Jirtle, Randy L.

    2012-10-11

    The overall hypothesis of this grant application is that low dose ionizing radiation (LDIR) elicits adaptive responses in part by causing heritable DNA methylation changes in the epigenome. This novel postulate was tested by determining if the level of DNA methylation at the Agouti viable yellow (A{sup vy}) metastable locus is altered, in a dose-dependent manner, by low dose radiation exposure (<10 cGy) during early gestation. This information is particularly important to ascertain given the increased use of CT scans in disease diagnosis, increased number of people predicted to live and work in space, and the present concern about radiological terrorism. We showed for the first time that LDIR significantly increased DNA methylation at the A{sup vy} locus in a sex-specific manner (p=0.004). Average DNA methylation was significantly increased in male offspring exposed to doses between 0.7 cGy and 7.6 cGy with maximum effects at 1.4 cGy and 3.0 cGy (p<0.01). Offspring coat color was concomitantly shifted towards pseudoagouti (p<0.01). Maternal dietary antioxidant supplementation mitigated both the DNA methylation changes and coat color shift in the irradiated offspring (p<0.05). Thus, LDIR exposure during gestation elicits epigenetic alterations that lead to positive adaptive phenotypic changes that are negated with antioxidants, indicating they are mediated in part by oxidative stress. These findings provide evidence that in the isogenic Avy mouse model epigenetic alterations resulting from LDIR play a role in radiation hormesis, bringing into question the assumption that every dose of radiation is harmful. Our findings not only have significant implications concerning the mechanism of hormesis, but they also emphasize the potential importance of this phenomenon in determining human risk at low radiation doses. Since the epigenetic regulation of genes varies markedly between species, the effect of LDIR on other epigenetically labile genes (e.g. imprinted genes) in

  17. Rhubarb extract partially improves mucosal integrity in chemotherapy-induced intestinal mucositis

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    Bajic, Juliana E; Eden, Georgina L; Lampton, Lorrinne S; Cheah, Ker Y; Lymn, Kerry A; Pei, Jinxin V; Yool, Andrea J; Howarth, Gordon S

    2016-01-01

    AIM To investigate the effects of orally gavaged aqueous rhubarb extract (RE) on 5-fluorouracil (5-FU)-induced intestinal mucositis in rats. METHODS Female Dark Agouti rats (n = 8/group) were gavaged daily (1 mL) with water, high-dose RE (HDR; 200 mg/kg) or low-dose RE (LDR; 20mg/kg) for eight days. Intestinal mucositis was induced (day 5) with 5-FU (150 mg/kg) via intraperitoneal injection. Intestinal tissue samples were collected for myeloperoxidase (MPO) activity and histological examination. Xenopus oocytes expressing aquaporin 4 water channels were prepared to examine the effect of aqueous RE on cell volume, indicating a potential mechanism responsible for modulating net fluid absorption and secretion in the gastrointestinal tract. Statistical significance was assumed at P < 0.05 by one-way ANOVA. RESULTS Bodyweight was significantly reduced in rats administered 5-FU compared to healthy controls (P < 0.01). Rats administered 5-FU significantly increased intestinal MPO levels (≥ 307%; P < 0.001), compared to healthy controls. However, LDR attenuated this effect in 5-FU treated rats, significantly decreasing ileal MPO activity (by 45%; P < 0.05), as compared to 5-FU controls. 5-FU significantly reduced intestinal mucosal thickness (by ≥ 29% P < 0.001) as compared to healthy controls. LDR significantly increased ileal mucosal thickness in 5-FU treated rats (19%; P < 0.05) relative to 5-FU controls. In xenopus oocytes expressing AQP4 water channels, RE selectively blocked water influx into the cell, induced by a decrease in external osmotic pressure. As water efflux was unaltered by the presence of extracellular RE, the directional flow of water across the epithelial barrier, in the presence of extracellular RE, indicated that RE may alleviate water loss across the epithelial barrier and promote intestinal health in chemotherapy-induced intestinal mucositis. CONCLUSION In summary, low dose RE improves selected parameters of mucosal integrity and reduces ileal

  18. Betulinic acid regulates generation of neuroinflammatory mediators responsible for tissue destruction in multiple sclerosis in vitro

    Institute of Scientific and Technical Information of China (English)

    Jana BLA(Z)EVSKI; Filip PETKOVI(C); Miljana MOM(C)ILOVI(C); Reinhard PASCHKE; Goran N KALUDEROVI(C); Marija MOSTARICA STOJKOVI(C); Djordje MILJKOVI(C)

    2013-01-01

    Aim:To investigate the influences of betulinic acid (BA),a triterpenoid isolated from birch bark,on neuroinflammatory mediators involved in the pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis in vitro.Methods:Encephalitogenic T cells were prepared from draining lymph nodes and spinal cords of Dark Agouti rats 8 to 10 d after immunization with myelin basic protein (MBP) and complete Freund's adjuvant.Macrophages were isolated from the peritoneal cavity of adult untreated rats.Astrocytes were isolated from neonatal rat brains.The cells were cultured and then treated with different agents.IFN-y,IL-17,iNOS and CXCL12 mRNA levels in the cells were analyzed with RT-PCR.iNOS and CXCL12 protein levels were detected using immunoblot.NO and ROS generation was measured using Griess reaction and flow cytometry,respectively.Results:In encephalitogenic T cells stimulated with MBP (10 μg/mL),addition of BA inhibited IL-17 and IFN-γ production in a dosedependent manner.The estimated IC50 values for IL-17 and IFN y were 11.2 and 63.8 μmol/L,respectively.When the macrophages were stimulated with LPS (10 ng/mL),addition of BA (50 μmol/L) significantly increased ROS generation,and suppressed NO generation.The astrocytes were stimulated with ConASn containing numerous inflammatory mediators,which mimicked the inflammatory milieu within CNS; addition of BA (50 μmol/L) significantly increased ROS generation,and blocked ConASn-induced increases in iNOS and CXCL12 mRNA levels,but did not affect iNOS and CXCL12 protein levels.Importantly,in both the macrophages and astrocytes,addition of BA (50 μmol/L) inhibited lipid peroxidation.Conclusion:Besides inhibiting encephalitogenic T cell cytokines and reducing NO generation,BA induces tissue-damaging ROS generation within CNS.

  19. Somato-dendritic localization and signaling by leptin receptors in hypothalamic POMC and AgRP neurons.

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    Sangdeuk Ha

    Full Text Available Leptin acts via neuronal leptin receptors to control energy balance. Hypothalamic pro-opiomelanocortin (POMC and agouti-related peptide (AgRP/Neuropeptide Y (NPY/GABA neurons produce anorexigenic and orexigenic neuropeptides and neurotransmitters, and express the long signaling form of the leptin receptor (LepRb. Despite progress in the understanding of LepRb signaling and function, the sub-cellular localization of LepRb in target neurons has not been determined, primarily due to lack of sensitive anti-LepRb antibodies. Here we applied light microscopy (LM, confocal-laser scanning microscopy (CLSM, and electron microscopy (EM to investigate LepRb localization and signaling in mice expressing a HA-tagged LepRb selectively in POMC or AgRP/NPY/GABA neurons. We report that LepRb receptors exhibit a somato-dendritic expression pattern. We further show that LepRb activates STAT3 phosphorylation in neuronal fibers within several hypothalamic and hindbrain nuclei of wild-type mice and rats, and specifically in dendrites of arcuate POMC and AgRP/NPY/GABA neurons of Leprb (+/+ mice and in Leprb (db/db mice expressing HA-LepRb in a neuron specific manner. We did not find evidence of LepRb localization or STAT3-signaling in axon-fibers or nerve-terminals of POMC and AgRP/NPY/GABA neurons. Three-dimensional serial EM-reconstruction of dendritic segments from POMC and AgRP/NPY/GABA neurons indicates a high density of shaft synapses. In addition, we found that the leptin activates STAT3 signaling in proximity to synapses on POMC and AgRP/NPY/GABA dendritic shafts. Taken together, these data suggest that the signaling-form of the leptin receptor exhibits a somato-dendritic expression pattern in POMC and AgRP/NPY/GABA neurons. Dendritic LepRb signaling may therefore play an important role in leptin's central effects on energy balance, possibly through modulation of synaptic activity via post-synaptic mechanisms.

  20. Supplementation of branched-chain amino acids to a reduced-protein diet improves growth performance in piglets: involvement of increased feed intake and direct muscle growth-promoting effect.

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    Zheng, Liufeng; Wei, Hongkui; Cheng, Chuanshang; Xiang, Quanhang; Pang, Jiaman; Peng, Jian

    2016-06-01

    The aim of this study was to investigate whether supplementing branched-chain amino acids (AA) (BCAA) along with a reduced-protein diet increases piglet growth, and whether elevated feed intake and muscle growth-promoting effect contribute to this improvement. In Expt 1, twenty-eight weanling piglets were randomly fed one of the following four diets: a positive control (PC) diet, a reduced-protein negative control (NC) diet, an NC diet supplemented with BCAA to the same levels as in the PC diet (test 1 (T1)) and an NC diet supplemented with a 2-fold dose of BCAA in T1 diet (test 2 (T2)) for 28 d. In Expt 2, twenty-one weanling piglets were randomly assigned to NC, T1 and pair-fed T1 (P) groups. NC and T1 diets were the same as in Expt 1, whereas piglets in the P group were individually pair-fed with the NC group. In Expt 1, the NC group had reduced piglet growth and feed intake compared with the PC group, which were restored in T1 and T2 groups, but no differences were detected between T1 and T2 groups. In Expt 2, T1 and P groups showed increases in growth and mass of some muscles compared with the NC group. Increased feed intake after BCAA supplementation was associated with increased mRNA expressions of agouti-related peptide and co-express neuropeptide Y (NPY) and phosphorylation of mammalian target of rapamycin (mTOR) and ribosomal protein S6 kinase 1 (S6K1), as well as decreased mRNA expressions of melanocortin-4 receptor and cocaine- and amphetamine-regulated transcript and phosphorylation of eukaryotic initiation factor 2α in the hypothalamus. No differences were observed among PC, T1 and T2 groups except for higher NPY mRNA expression in the T2 group than in the PC group (Expt 1). Phosphorylation of mTOR and S6K1 in muscle was enhanced after BCAA supplementation, which was independent of change in feed intake (Expt 2). In conclusion, supplementing BCAA to reduced-protein diets increases feed intake and muscle mass, and contributes to better growth

  1. Changes in interleukin-1 signal modulators induced by 3,4-methylenedioxymethamphetamine (MDMA: regulation by CB2 receptors and implications for neurotoxicity

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    O'Shea Esther

    2011-05-01

    Full Text Available Abstract Background 3,4-Methylenedioxymethamphetamine (MDMA produces a neuroinflammatory reaction in rat brain characterized by an increase in interleukin-1 beta (IL-1β and microglial activation. The CB2 receptor agonist JWH-015 reduces both these changes and partially protects against MDMA-induced neurotoxicity. We have examined MDMA-induced changes in IL-1 receptor antagonist (IL-1ra levels and IL-1 receptor type I (IL-1RI expression and the effects of JWH-015. The cellular location of IL-1β and IL-1RI was also examined. MDMA-treated animals were given the soluble form of IL-1RI (sIL-1RI and neurotoxic effects examined. Methods Dark Agouti rats received MDMA (12.5 mg/kg, i.p. and levels of IL-1ra and expression of IL-1RI measured 1 h, 3 h or 6 h later. JWH-015 (2.4 mg/kg, i.p. was injected 48 h, 24 h and 0.5 h before MDMA and IL-1ra and IL-1RI measured. For localization studies, animals were sacrificed 1 h or 3 h following MDMA and stained for IL-1β or IL-1RI in combination with neuronal and microglial markers. sIL-1RI (3 μg/animal; i.c.v. was administered 5 min before MDMA and 3 h later. 5-HT transporter density was determined 7 days after MDMA injection. Results MDMA produced an increase in IL-ra levels and a decrease in IL-1RI expression in hypothalamus which was prevented by CB2 receptor activation. IL-1RI expression was localized on neuronal cell bodies while IL-1β expression was observed in microglial cells following MDMA. sIL-1RI potentiated MDMA-induced neurotoxicity. MDMA also increased IgG immunostaining indicating that blood brain-barrier permeability was compromised. Conclusions In summary, MDMA produces changes in IL-1 signal modulators which are modified by CB2 receptor activation. These results indicate that IL-1β may play a partial role in MDMA-induced neurotoxicity.

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

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    Andrés F. PEÑA-CRUZ

    2015-01-01

    Full Text Available 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 cinco, especialmente en l ( longhair y c s ( siamese . Dichas diferencias pueden atribuirse a la selección humana de características más atractivas y por el flujo génico resultante del crecimiento demográfico de la ciudad, lo que explicaría también el primer reporte de los alelos inhibitor y ticked abyssinian . Se evaluó el equilibrio Hardy-Weinberg para el norte, sur y las dos zonas juntas, usando los loci white spotting y orange , encontrándose desequilibrio en este último para las tres zonas evaluadas debido a un déficit de heterocigotos. Norte y sur se dividieron en dos, y cada sub-muestra presentó equilibrio Hardy-Weinberg, aunque las diferencias en las frecuencias alélicas y heterocigosidades resaltaron microestructura geográfica y una relación entre tiempo de fundación del barrio y heterocigosidad. Norte y sur resultaron ser una población y no subpoblaciones (F ST = 0,0004, D= 0,0017, al igual que las nueve poblaciones colombianas con las que se comparó la presente ciudad. Se sugiere realizar un análisis microgeográfico de flujo génico y la definición de posibles colonias de gatos en Cali.

  3. Increase of long-term 'diabesity' risk, hyperphagia, and altered hypothalamic neuropeptide expression in neonatally overnourished 'small-for-gestational-age' (SGA rats.

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    Karen Schellong

    Full Text Available BACKGROUND: Epidemiological data have shown long-term health adversity in low birth weight subjects, especially concerning the metabolic syndrome and 'diabesity' risk. Alterations in adult food intake have been suggested to be causally involved. Responsible mechanisms remain unclear. METHODS AND FINDINGS: By rearing in normal (NL vs. small litters (SL, small-for-gestational-age (SGA rats were neonatally exposed to either normal (SGA-in-NL or over-feeding (SGA-in-SL, and followed up into late adult age as compared to normally reared appropriate-for-gestational-age control rats (AGA-in-NL. SGA-in-SL rats displayed rapid neonatal weight gain within one week after birth, while SGA-in-NL growth caught up only at juvenile age (day 60, as compared to AGA-in-NL controls. In adulthood, an increase in lipids, leptin, insulin, insulin/glucose-ratio (all p<0.05, and hyperphagia under normal chow as well as high-energy/high-fat diet, modelling modern 'westernized' lifestyle, were observed only in SGA-in-SL as compared to both SGA-in-NL and AGA-in-NL rats (p<0.05. Lasercapture microdissection (LMD-based neuropeptide expression analyses in single neuron pools of the arcuate hypothalamic nucleus (ARC revealed a significant shift towards down-regulation of the anorexigenic melanocortinergic system (proopiomelanocortin, Pomc in SGA-in-SL rats (p<0.05. Neuropeptide expression within the orexigenic system (neuropeptide Y (Npy, agouti-related-peptide (Agrp and galanin (Gal was not significantly altered. In essence, the 'orexigenic index', proposed here as a neuroendocrine 'net-indicator', was increased in SGA-in-SL regarding Npy/Pomc expression (p<0.01, correlated to food intake (p<0.05. CONCLUSION: Adult SGA rats developed increased 'diabesity' risk only if exposed to neonatal overfeeding. Hypothalamic malprogramming towards decreased anorexigenic activity was involved into the pathophysiology of this neonatally acquired adverse phenotype. Neonatal overfeeding

  4. Induction of Foxp3-expressing regulatory T-cells by donor blood transfusion is required for tolerance to rat liver allografts.

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    Yuta Abe

    Full Text Available BACKGROUND: Donor-specific blood transfusion (DST prior to solid organ transplantation has been shown to induce long-term allograft survival in the absence of immunosuppressive therapy. Although the mechanisms underlying DST-induced allograft tolerance are not well defined, there is evidence to suggest DST induces one or more populations of antigen-specific regulatory cells that suppress allograft rejection. However, neither the identity nor the regulatory properties of these tolerogenic lymphocytes have been reported. Therefore, the objective of this study was to define the kinetics, phenotype and suppressive function of the regulatory cells induced by DST alone or in combination with liver allograft transplantation (LTx. METHODOLOGY/PRINCIPAL FINDINGS: Tolerance to Dark Agouti (DA; RT1(a rat liver allografts was induced by injection (iv of 1 ml of heparinized DA blood to naïve Lewis (LEW; RT1(l rats once per week for 4 weeks prior to LTx. We found that preoperative DST alone generates CD4(+ T-cells that when transferred into naïve LEW recipients are capable of suppressing DA liver allograft rejection and promoting long-term survival of the graft and recipient. However, these DST-generated T-cells did not express the regulatory T-cell (Treg transcription factor Foxp3 nor did they suppress alloantigen (DA-induced activation of LEW T-cells in vitro suggesting that these lymphocytes are not fully functional regulatory Tregs. We did observe that DST+LTx (but not DST alone induced the time-dependent formation of CD4(+Foxp3(+ Tregs that potently suppressed alloantigen-induced activation of naïve LEW T-cells in vitro and liver allograft rejection in vivo. Finally, we present data demonstrating that virtually all of the Foxp3-expressing Tregs reside within the CD4(+CD45RC(- population whereas in which approximately 50% of these Tregs express CD25. CONCLUSIONS/SIGNIFICANCE: We conclude that preoperative DST, in the absence of liver allograft

  5. Epigenetic Effects of Environmental Chemicals Bisphenol A and Phthalates

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    Steven Shoei-Lung Li

    2012-08-01

    Full Text Available The epigenetic effects on DNA methylation, histone modification, and expression of non-coding RNAs (including microRNAs of environmental chemicals such as bisphenol A (BPA and phthalates have expanded our understanding of the etiology of human complex diseases such as cancers and diabetes. Multiple lines of evidence from in vitro and in vivo models have established that epigenetic modifications caused by in utero exposure to environmental toxicants can induce alterations in gene expression that may persist throughout life. Epigenetics is an important mechanism in the ability of environmental chemicals to influence health and disease, and BPA and phthalates are epigenetically toxic. The epigenetic effect of BPA was clearly demonstrated in viable yellow mice by decreasing CpG methylation upstream of the Agouti gene, and the hypomethylating effect of BPA was prevented by maternal dietary supplementation with a methyl donor like folic acid or the phytoestrogen genistein. Histone H3 was found to be trimethylated at lysine 27 by BPA effect on EZH2 in a human breast cancer cell line and mice. BPA exposure of human placental cell lines has been shown to alter microRNA expression levels, and specifically, miR-146a was strongly induced by BPA treatment. In human breast cancer MCF7 cells, treatment with the phthalate BBP led to demethylation of estrogen receptor (ESR1 promoter-associated CpG islands, indicating that altered ESR1 mRNA expression by BBP is due to aberrant DNA methylation. Maternal exposure to phthalate DEHP was also shown to increase DNA methylation and expression levels of DNA methyltransferases in mouse testis. Further, some epigenetic effects of BPA and phthalates in female rats were found to be transgenerational. Finally, the available new technologies for global analysis of epigenetic alterations will provide insight into the extent and patterns of alterations between human normal and diseased tissues.

  6. Expression of Selenoprotein Genes Is Affected by Obesity of Pigs Fed a High-Fat Diet123

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    Zhao, Hua; Li, Ke; Tang, Jia-Yong; Zhou, Ji-Chang; Wang, Kang-Ning; Xia, Xin-Jie; Lei, Xin Gen

    2015-01-01

    Background: Relations of the 25 mammalian selenoprotein genes with obesity and the associated inflammation remain unclear. Objective: This study explored impacts of high-fat diet-induced obesity on inflammation and expressions of selenoprotein and obesity-related genes in 10 tissues of pigs. Methods: Plasma and 10 tissues were collected from pigs (n = 10) fed a corn-soy–based control diet or that diet containing 3–7% lard from weanling to finishing (180 d). Plasma concentrations (n = 8) of cytokines and thyroid hormones and tissue mRNA abundance (n = 4) of 25 selenoprotein genes and 16 obesity-related genes were compared between the pigs fed the control and high-fat diets. Stepwise regression was applied to analyze correlations among all these measures, including the previously reported body physical and plasma biochemical variables. Results: The high-fat diet elevated (P < 0.05) plasma concentrations of tumor necrosis factor α, interleukin-6, leptin, and leptin receptor by 29–42% and affected (P < 0.05–0.1) tissue mRNA levels of the selenoprotein and obesity-related genes in 3 patterns. Specifically, the high-fat diet up-regulated 12 selenoprotein genes in 6 tissues, down-regulated 13 selenoprotein genes in 7 tissues, and exerted no effect on 5 genes in any tissue. Body weights and plasma triglyceride concentrations of pigs showed the strongest regressions to tissue mRNA abundances of selenoprotein and obesity-related genes. Among the selenoprotein genes, selenoprotein V and I were ranked as the strongest independent variables for the regression of phenotypic and plasma measures. Meanwhile, agouti signaling protein, adiponectin, and resistin genes represented the strongest independent variables of the obesity-related genes for the regression of tissue selenoprotein mRNA. Conclusions: The high-fat diet induced inflammation in pigs and affected their gene expression of selenoproteins associated with thioredoxin and oxidoreductase systems, local tissue

  7. Transcriptional evidence for the role of chronic venlafaxine treatment in neurotrophic signaling and neuroplasticity including also Glutamatergic [corrected] - and insulin-mediated neuronal processes.

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    Viola Tamási

    Full Text Available Venlafaxine (VLX, a serotonine-noradrenaline reuptake inhibitor, is one of the most commonly used antidepressant drugs in clinical practice for the treatment of major depressive disorder (MDD. Despite being more potent than its predecessors, similarly to them, the therapeutical effect of VLX is visible only 3-4 weeks after the beginning of treatment. Furthermore, recent papers show that antidepressants, including also VLX, enhance the motor recovery after stroke even in non depressed persons. In the present, transcriptomic-based study we looked for changes in gene expressions after a long-term VLX administration.Osmotic minipumps were implanted subcutaneously into Dark Agouti rats providing a continuous (40 mg/kg/day VLX delivery for three weeks. Frontal regions of the cerebral cortex were isolated and analyzed using Illumina bead arrays to detect genes showing significant chances in expression. Gene set enrichment analysis was performed to identify specific regulatory networks significantly affected by long term VLX treatment.Chronic VLX administration may have an effect on neurotransmitter release via the regulation of genes involved in vesicular exocytosis and receptor endocytosis (such as Kif proteins, Myo5a, Sv2b, Syn2 or Synj2. Simultaneously, VLX activated the expression of genes involved in neurotrophic signaling (Ntrk2, Ntrk3, glutamatergic transmission (Gria3, Grin2b and Grin2a, neuroplasticity (Camk2g/b, Cd47, synaptogenesis (Epha5a, Gad2 and cognitive processes (Clstn2. Interestingly, VLX increased the expression of genes involved in mitochondrial antioxidant activity (Bcl2 and Prdx1. Additionally, VLX administration also modulated genes related to insulin signaling pathway (Negr1, Ppp3r1, Slc2a4 and Enpp1, a mechanism that has recently been linked to neuroprotection, learning and memory.Our results strongly suggest that chronic VLX treatment improves functional reorganization and brain plasticity by influencing gene expression in

  8. Peptides and Food Intake

    Science.gov (United States)

    Sobrino Crespo, Carmen; Perianes Cachero, Aránzazu; Puebla Jiménez, Lilian; Barrios, Vicente; Arilla Ferreiro, Eduardo

    2014-01-01

    The mechanisms for controlling food intake involve mainly an interplay between gut, brain, and adipose tissue (AT), among the major organs. Parasympathetic, sympathetic, and other systems are required for communication between the brain satiety center, gut, and AT. These neuronal circuits include a variety of peptides and hormones, being ghrelin the only orexigenic molecule known, whereas the plethora of other factors are inhibitors of appetite, suggesting its physiological relevance in the regulation of food intake and energy homeostasis. Nutrients generated by food digestion have been proposed to activate G-protein-coupled receptors on the luminal side of enteroendocrine cells, e.g., the L-cells. This stimulates the release of gut hormones into the circulation such as glucagon-like peptide-1 (GLP-1), oxyntomodulin, pancreatic polypeptides, peptide tyrosine tyrosine, and cholecystokinin, which inhibit appetite. Ghrelin is a peptide secreted from the stomach and, in contrast to other gut hormones, plasma levels decrease after a meal and potently stimulate food intake. Other circulating factors such as insulin and leptin relay information regarding long-term energy stores. Both hormones circulate at proportional levels to body fat content, enter the CNS proportionally to their plasma levels, and reduce food intake. Circulating hormones can influence the activity of the arcuate nucleus (ARC) neurons of the hypothalamus, after passing across the median eminence. Circulating factors such as gut hormones may also influence the nucleus of the tractus solitarius (NTS) through the adjacent circumventricular organ. On the other hand, gastrointestinal vagal afferents converge in the NTS of the brainstem. Neural projections from the NTS, in turn, carry signals to the hypothalamus. The ARC acts as an integrative center, with two major subpopulations of neurons influencing appetite, one of them coexpressing neuropeptide Y and agouti-related protein (AgRP) that increases food

  9. Intermittent Moderate Energy Restriction Improves Weight Loss Efficiency in Diet-Induced Obese Mice.

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    Radhika V Seimon

    Full Text Available Intermittent severe energy restriction is popular for weight management. To investigate whether intermittent moderate energy restriction may improve this approach by enhancing weight loss efficiency, we conducted a study in mice, where energy intake can be controlled.Male C57/Bl6 mice that had been rendered obese by an ad libitum diet high in fat and sugar for 22 weeks were then fed one of two energy-restricted normal chow diets for a 12-week weight loss phase. The continuous diet (CD provided 82% of the energy intake of age-matched ad libitum chow-fed controls. The intermittent diet (ID provided cycles of 82% of control intake for 5-6 consecutive days, and ad libitum intake for 1-3 days. Weight loss efficiency during this phase was calculated as (total weight change ÷ [(total energy intake of mice on CD or ID-(total average energy intake of controls]. Subsets of mice then underwent a 3-week weight regain phase involving ad libitum re-feeding.Mice on the ID showed transient hyperphagia relative to controls during each 1-3-day ad libitum feeding period, and overall ate significantly more than CD mice (91.1±1.0 versus 82.2±0.5% of control intake respectively, n = 10, P<0.05. There were no significant differences between CD and ID groups at the end of the weight loss or weight regain phases with respect to body weight, fat mass, circulating glucose or insulin concentrations, or the insulin resistance index. Weight loss efficiency was significantly greater with ID than with CD (0.042±0.007 versus 0.018±0.001 g/kJ, n = 10, P<0.01. Mice on the CD exhibited significantly greater hypothalamic mRNA expression of proopiomelanocortin (POMC relative to ID and control mice, with no differences in neuropeptide Y or agouti-related peptide mRNA expression between energy-restricted groups.Intermittent moderate energy restriction may offer an advantage over continuous moderate energy restriction, because it induces significantly greater weight loss relative

  10. Secreted phospholipase A2 activity in experimental autoimmune encephalomyelitis and multiple sclerosis

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    Blankenhorn Elizabeth P

    2006-09-01

    Full Text Available Abstract Background There is increased interest in the contribution of the innate immune system to multiple sclerosis (MS, including the activity of acute inflammatory mediators. The purpose of this study was to test the involvement of systemic secreted phospholipase A2 (sPLA2 enzymes in experimental autoimmune encephalomyelitis (EAE, an MS model, and to determine if enzyme activity is elevated in MS patients. Methods A non-invasive urinary assay was developed in order to monitor enzymatically active sPLA2 levels in Dark Agouti rats after induction of EAE. Some Rats were treated with nonapeptide CHEC-9, an uncompetitive sPLA2 enzyme inhibitor, during the initial rise in urinary enzyme levels. Body weight and clinical EAE score were measured for 18 days post immunization (PI, after which the rats were sacrificed for H&E and myelin staining, and for ED-1 immunocytochemistry, the latter to quantify macrophages and activated microglia. The urinary sPLA2 assay was also applied to un-timed samples collected from a cross section of 44 MS patients and 14 healthy controls. Results Mean levels of enzymatically active sPLA2 in the urine increased following immunization and peaked between days 8–10 PI which was just prior to the onset of EAE symptoms. At this time, a transient attenuation of activity was detected in the urine of CHEC-9 treated rats consistent with the activity-dependent properties of the inhibitor. The peptide also reduced or abolished EAE symptoms compared to vehicle-injected controls. Histopathological changes in the spinal cords of the EAE rats correlated generally with clinical score including a significant reduction in ED-1+ cells after peptide treatment. Multiple Sclerosis patients also showed elevations in sPLA2 enzyme activity. Mean levels of sPLA2 were increased 6-fold in the urine of patients with active disease and 4-fold for patients in remission, regardless of immunomodulating therapy. Conclusion The results suggest that s

  11. - Un modelo descriptivo del sistema reproductor hembra del coipo (Myocastor coypus I: el ovario (A descriptive model of the female reproductive system of coypu (Myocastor coypus I: the ovary

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    Felipe, A. E.

    2005-12-01

    conformada por tejido conectivo en disposición plexiforme, en el cual las fibras se orientaron en todas direcciones. Se observaron también fibras elásticas y argentófilas. En los ejemplares estudiados fue posible identificar todos los tipos foliculares y determinar la presencia de distintos grados de atresia correspondientes a folículos en diferentes etapas de desarrollo. Los folículos en crecimiento (secundarios atrésicos se caracterizaron por el engrosamiento de la zona pelúcida, la vacuolización citoplasmática de células foliculares, picnosis, vacuolización de la teca interna y tejido conectivo de sustitución. Con respecto a las estructuras consideradas como cuerpos lúteos, pudieron establecerse y caracterizarse tres grados de desarrollo de los mismos (inicial, medio y maduro así como determinarse diferentes estadíos de regresión o atresia. Todos los ovarios del coipo contuvieron cuerpos lúteos accesorios. Los mismos se diferenciaron de los verdaderos por su menor tamaño y la persistencia de un remanente ovocitario con una zona pelúcida degenerada. El diámetro medio de estas estructuras fue de 273.44 ± 78.22 mm. Las observaciones presentadas en este trabajo indican que el ovario de coipos sexualmente maduros es semejante al de otros mamíferos como la chinchilla (Chinchilla laniger, el cobayo (Cavia sp., la casiragua (Proechimys guairae, el carpincho (Hydrochoerus hydrochaeris, la mara (Dolichotis patagonum, el aguti (Dasyprocta aguti, el puercoespín africano austral (Hystrix africaeaustralis y el puercoespín africano común (Atherurus africanus. In the present investigation mature females of coypu (Myocastor coypus were used to determine the anatomic and histomorphologic features of the ovaries. As in all mammals, the ovary was suspended from the dorsal wall of the peritoneal cavity by the mesovarium. In the studied animals, the mesovarium did not form a bursa. The ovary of the coypu is similar to the ovary of other adult hystricomorph rodents: it

  12. Combate ao Desmodus rotundus rotundus (E. Geoffroy,1810 na região cárstica de Cordisburgo e Curvelo, Minas Gerais Combat of Desmodus rotundus rotundus (E. Geofroy, 1810 in the Cordisburgo and Curvelo carstic region, Minas Gerais, Brazil

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    E.O. Almeida

    2002-04-01

    Full Text Available Com o objetivo de avaliar em uma região cárstica o tipo de refúgio, as espécies de morcegos, a população de animais domésticos, as associações interespecíficas nas coabitações com outros mamíferos silvestres suscetíveis à raiva e a eficácia da warfarina aplicada no dorso do Desmodus rotundus rotundus foi realizada uma pesquisa de maio de 1998 a março de 2000, nos municípios de Cordisburgo e Curvelo, Minas Gerais. Em 49 refúgios vistoriados, 29 naturais e 20 artificiais, localizados em 14 propriedades, encontrou-se o Desmodus rotundus rotundus em 18 abrigos naturais. Destes, 17 eram cavernas formadas pela dissolução ou abatimento de rocha calcária, típica do carste, e um era túnel escavado na terra pela ação das águas de um rio. As características geomorfológicas e de localização espacial foram registradas com base nas coordenadas geográficas, obtidas com auxílio de um sensor geográfico de posição. Nesses abrigos foram capturados e identificados 1457 morcegos de 14 espécies, sendo 640 Glossophaga soricina (Pallas, 1766, 566 Desmodus rotundus (E. Geoffroy, 1810, 73 Anoura geoffroyi (Gray 1838, 58 Trachops cirrhosus (Spix, 1823, 38 Diphylla ecaudata ecaudata (Spix, 1823, 23 Platyhrrinus lineatus (E. Geoffroy, 1810, 16 Lasiurus ega (Gervais, 1856, 14 Carollia perspicillata (Linnaeus, 1758, 13 Phyllostomus hastatus hastatus (Pallas, 1767, 9 Artibeus lituratus (Olfers, 1818, 3 Mimmon bennettii (Gray, 1838, 2 Myotis nigricans (Schinz, 1821, 1 Eptesicus brasiliensis (Desmarest, 1819 e 1 Pygoderma bilabiatum (Wagner, 1843. Não se conseguiu isolar ou detectar o vírus rábico no cérebro de 25 hematófagos selecionados e em 52 de outras espécies. A maioria desses abrigos também era usada por pacas (Agouti paca Linnaues, 1766, capivaras (Hydrochaeris hydrochaeris, Linnaues, 1766, guaxinins (Procyon cancrivorus, G. Cuvier, 1798 e raposas (Lycalopex vetulus, Lund, 1842 que são suscetíveis à raiva. Em 546 Desmodus

  13. Neuropeptides and obesity.

    Science.gov (United States)

    Beck, B

    2000-10-01

    This review focuses on the expression, content, and release of neuropeptides and on their role in the development of obesity in animal models with single-gene mutations. The balance between neuropeptides that contribute to the control of feeding behavior is profoundly and variously altered in these models, supporting the concept of the existence of several types of obesity. The hypothalamic neuropeptide Y (NPY) and the pro-opiomelanocortin (POMC) systems are the networks most studied in relation to energy intake. Both receive information about the nutritional status and the level of energy storage through insulin and leptin signaling mediated by specific receptors located on POMC and NPY neurons present predominantly in the arcuate nucleus (ARC). When leptin signaling is defective, through a defect in either the receptor (Zucker fa/fa rat, cp/cp rat, and db/db mouse) or in the peptide itself (ob/ob mouse), the NPY system is upregulated as shown by mRNA overexpression and increased peptide release, whereas the content and/or release of some inhibitory peptides (neurotensin, cholecystokinin) are diminished. For the POMC system, there is a complex interaction between the tonic inhibition of food intake exerted by alpha-melanocyte-stimulating hormone (alpha-MSH) and the Agouti-related protein at the level of the type 4 melanocortin receptor. The latter peptide is coexpressed with NPY in the ARC. Corticotropin-releasing factor (CRF) is the link between food intake and environmental factors. It not only inhibits food intake and prevents weight gain, likely through hypothalamic effects, but also activates the hypothalamo-pituitary axis and therefore contributes to energy storage in adipose tissue. The factors that prod the CRF system toward the hypothalamic or hypothalamo-pituitary axis system remain to be more clearly defined (comodulators, connections between limbic system and ARC, cellular location, and type of receptors, etc. ). The pathways used by all of these

  14. A closer look at evolution: Variants (SNPs) of genes involved in skin pigmentation, including EXOC2, TYR, TYRP1, and DCT, are associated with 25(OH)D serum concentration.

    Science.gov (United States)

    Saternus, Roman; Pilz, Stefan; Gräber, Stefan; Kleber, Marcus; März, Winfried; Vogt, Thomas; Reichrath, Jörg

    2015-01-01

    Vitamin D deficiency is common in the Caucasian population and is associated with increased incidence and unfavorable outcome of many diseases, including various types of cancer, infectious, cardiovascular, and autoimmune diseases. Individual factors that predispose for a person's vitamin D status, such as skin type, have been identified, but limited data exist on genetic determinants of serum 25-hydroxyvitamin D (25[OH]D) concentration. We have tested the hypothesis that variants of genes (single nucleotide polymorphisms [SNPs]) involved in skin pigmentation are predictive of serum 25(OH)D levels. Serum 25(OH)D and SNPs (n = 960) related to genes with relevance for skin pigmentation (tyrosinase [TYR], TYR-related protein 1 [TYRP1], dopachrome tautomerase [DCT], oculocutaneous albinism II [OCA2], two pore segment channel 2 [TPCN2], solute carrier family 24 A4 [SLC24A4], solute carrier family 45 A2 [SLC45A2], agouti signalling peptide [ASIP], cyclic AMP-dependent transcription factor [ATF1], microphthalmia-associated transcription factor [MITF], proopiomelanocortin [POMC], cAMP-dependent protein kinase catalytic subunit beta [PRKACB], cAMP-dependent protein kinase catalytic subunit gamma [PRKACG], cAMP-dependent protein kinase type I-alpha regulatory subunit [PRKAR1A], cAMP-dependent protein kinase type II-alpha regulatory subunit [PRKAR2A], cAMP-dependent protein kinase type II-beta regulatory subunit [PRKAR2B], tubulin beta-3 chain/melanocortin receptor 1 [TUBB3/MC1R], Cadherin-1 [CDH1], catenin beta 1 [CTNNB1], Endothelin 1 [EDN1], endothelin 3 [EDN3], endothelin receptor type B [EDNRB], fibroblast growth factor 2 [FGF2], KIT, KIT ligand [KITLG], nerve growth factor [NGF], interferon regulatory factor 4 [IRF4], exocyst complex component 2 [EXOC2], and tumor protein 53 [TP53]) were analyzed in a cohort of participants of the Ludwigshafen Risk and Cardiovascular Health Study (n = 2970). A total of 46 SNPs were associated (P <.05) with lower or higher serum 25(OH

  15. Regulatory mechanisms of melanogenesis in human skin%人皮肤黑素生成调控机制的研究进展

    Institute of Scientific and Technical Information of China (English)

    倪亚杰; 王平

    2012-01-01

    Melanin in human skin is synthesized in the melanosomes of melanocytes,and there are many modes of regulation of melanogenesis,such as transcriptional regulation,regulation by intracellular signaling pathway,feedback regulation by products,and other positive(stimulation)or negative(inhibitory)regulation by nuclear receptors and cytokines.During the process of melanogenesis,microphthalmia transcription factor(MITF)plays a fundamental role in the regulation of tyrosinases and other tyrosinase-related proteins,with cyclic adenosine monophosphate/protein kinase A(cAMP/PKA)pathway,mitogen-activated protein kinase(MAPK)pathway,nitric oxide/cyclic guanosine monophosphate/protein kinase G(NO/cGMP/PKG)pathway and diacylglycerol/protein kinase C(DG/PKC)pathway as the four major intracellular signaling pathways.Some molecules and their receptors play positive(stimulating)roles in melanogenesis,such as G protein-coupled receptors and their ligands,stem cell growth factor and its receptor,nuclear receptors and their ligands,while some molecules and receptors play negative(inhibiting)roles,such as the Agouti signaling protein and its receptor,G protein-coupled receptors and their ligands,as well as cytokines,growth factors and their receptors.%人皮肤黑素在黑素细胞的黑素小体内合成,受多重因素的复杂调控,包括转录调节、细胞内信号传导通路调节、产物的反馈调节,以及核受体、细胞因子等对黑素生成的正向(刺激)和负向(抑制)调节.在正常黑素生成过程中,小眼畸形相关转录因子是转录调控酪氨酸酶及其相关蛋白的最重要分子;环磷酸腺苷/蛋白激酶A通路、丝裂原激活的蛋白激酶通路、一氧化氮/环磷酸鸟苷/蛋白激酶G通路、二酯酰甘油/蛋白激酶C通路是参与黑素生成的最主要4条细胞内信号传导通路.对黑素生成有正向(刺激)作用的分子及其受体主要有G蛋白耦联受体及其配体、干细胞生长

  16. Influence of reference genes on expression of TYR, MITF and ASIP genes in tissues of Silky Fowl%内参基因对 TYR、MITF和ASIP基因在白绒乌骨鸡各组织表达水平的影响

    Institute of Scientific and Technical Information of China (English)

    郑嫩珠; 李丽; 辛清武; 缪中纬; 朱志明; 刘凤辉; 吴俭飞; 卢立志

    2015-01-01

    that taking GA PD H as a reference gene , the expressionlevelof TYR,ASIPandMITFgeneswiththemelanincontentintissueshadthesametrend:skin >kidney > gizzard > liver > muscle , but the expression level of A SIP gene was opposite to melanin deposition content , which implied that each target gene expression was matched with their respective function on regulating melanin deposition . For instance , high expression of TYR and MITF genes promoted melanin deposition , while the ASIP gene inhibited melanin deposition . Taking 18S rRNA and ACTB as reference genes , the expression of TYR,MITFandASIPgeneswerenotrelatedtothemelanindeposition,andanidealcalibrationresultcouldnot be obtained . In conclusion , reference gene plays an important role in the expression of target gene . In this paper , GA PD H gene not only had highest expression stability in tissues , but also could truly reflect the regulation effect of the targetgenes(TYR,MITFandASIP) onmelanindeposition.Thus,GAPDHgeneisthemostsuitablereference gene for normalizing the mRNA expression of genes in tissues of Silky Fowl .%以健康白绒乌骨鸡肌肉、肾、肝、肌胃和皮肤为试验素材,应用实时荧光定量聚合酶链反应技术探讨β‐肌动蛋白(beta‐actin ,ACTB)、3‐磷酸甘油醛脱氢酶(glyceraldehyde‐3‐phosphate dehydrogenase ,GA PDH)和18S核糖体RNA(18S ribosomal RNA ,18S rRNA )3个内参基因的组织表达稳定性及其对酪氨酸酶( tyrosinase ,TYR)、小眼畸形相关转录因子(microphthalmia‐associated transcription factor ,MITF)和刺鼠信号蛋白(agouti signaling pro tein ,A S I P)等目的基因在白绒乌骨鸡各组织表达水平的影响,并采用紫外分光光度法分析各组织黑色素沉积规律,从中筛选出理想的内参基因.geNorm和NormFinder软件分析结果显示,内参基因GA PD H在白绒乌骨鸡各组织表达稳定性最高,ACTB表达稳定性最低.相对定量和黑色素沉积结果表明,GA PDH作为内参基因时,各组织 MITF

  17. Book Reviews

    Directory of Open Access Journals (Sweden)

    Redactie KITLV

    2001-07-01

    Full Text Available -Stanley L. Engerman, Heather Cateau ,Capitalism and slavery fifty years later: Eric Eustace Williams - A reassessment of the man and his work. New York: Peter Lang, 2000. xvii + 247 pp., S.H.H. Carrington (eds -Philip D. Morgan, B.W. Higman, Writing West Indian histories. London: Macmillan Caribbean, 1999. xiv + 289 pp. -Daniel Vickers, Alison Games, Migration and the origins of the English Atlantic world. Cambridge MA: Harvard University Press, 1999. xiii + 322 pp. -Christopher L. Brown, Andrew Jackson O'Shaughnessy, An empire divided: The American revolution and the British Caribbean. Philadelphia: University of Pennsylvania Press, 2000. xviii + 357 pp. -Lennox Honychurch, Samuel M. Wilson, The indigenous people of the Caribbean. Gainesville: University Press of Florida, 1997. xiv + 253 pp. -Kenneth Bilby, Bev Carey, The Maroon story: The authentic and original history of the Maroons in the history of Jamaica 1490-1880. St. Andrew, Jamaica: Agouti Press, 1997. xvi + 656 pp. -Bernard Moitt, Doris Y. Kadish, Slavery in the Caribbean Francophone world: Distant voices, forgotten acts, forged identities. Athens: University of Georgia Press, 2000. xxiii + 247 pp. -Michael J. Guasco, Virginia Bernhard, Slaves and slaveholders in Bermuda, 1616-1782. Columbia: University of Missouri Press, 1999. xviii + 316 pp. -Michael J. Jarvis, Roger C. Smith, The maritime heritage of the Cayman Islands. Gainesville: University Press of Florida, 2000. xxii + 230 pp. -Paul E. Hoffman, Peter R. Galvin, Patterns of pillage: A geography of Caribbean-based piracy in Spanish America, 1536-1718. New York: Peter Lang, 1999. xiv + 271 pp. -David M. Stark, Raúl Mayo Santana ,Cadenas de esclavitud...y de solidaridad: Esclavos y libertos en San Juan,siglo XIX. Río Piedras: Centro de Investigaciones Sociales, Universidad de Puerto Rico, 1997. 204 pp., Mariano Negrón Portillo, Manuel Mayo López (eds -Ada Ferrer, Philip A. Howard, Changing history: Afro-Cuban Cabildos and

  18. Desnutrición y amenorrea hipotalámica funcional: Neuropéptidos periféricos (Leptina, Adiponectina, Ghrelina y su relación con la homeostasis metabólica

    Directory of Open Access Journals (Sweden)

    León Fiszlejder

    2009-09-01

    AHF, promueve la oxidación de los ácidos grasos libres en el músculo esquelético, produce una reducción de triglicéridos en esos tejidos, inhibe directamente la captación y oxidación de los ácidos grasos libres en el hígado, disminuyendo también los triglicéridos en esta víscera. Estas acciones inducen el aumento de la sensibilidad a la insulina, una de las características en la patología de estas pacientes. Además, esta citokina disminuye la liberación de glucosa desde el hígado y músculo esquelético y estimula directamente la captación de glucosa en estos tejidos, mediante la activación de la AMP proteinkinasa. En consecuencia, la elevación de la adiponectina jugaría un rol de colaboración en el mantenimiento de la homeostasis metabólica-energética en condiciones de mal nutrición, como la que impera en la anorexia nerviosa y en otras causas de AHF. La osteosporosis, la inmunodepresión, el aumento del riesgo cardiovascular y la AHF pueden ser interpretados como efectos que derivan de procesos de adaptación que llevan a cabo hormonas hipotalámicas y neuropétidos periféricos. La amenorrea podría ser considerada un efecto protector.Functional hypothalamic amenorrhea (FHA is usually associated with an inadequate qualitative and quantitative diet which influences the energetic balance, modifies the body composition and produces hormonal reactions in order to keep metabolic homeostasis. This adaptive process is regulated by a "central circuit" (hypothalamic hormones, a "peripheral circuit" originated by adipocyte tissue (leptin, adiponectin, among other cytokines and the superior gastrointestinal tract through a neuropetide: ghrelin. Leptin acts in the hypothalamus stimulating the synthesis of MSH and inhibits the NPY and the AgRP (Agouti-related-peptide both with orexigen action. NPY stimulates CRH and both inhibit GnRH in the hypothalamus. Low levels of leptin in FHA increases NPY-CRH system blocking Gn-RH pulsatility, a key process in