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Sample records for metabolic functions including

  1. [Metabolic functions and sport].

    Riviere, Daniel

    2004-01-01

    Current epidemiological studies emphasize the increased of metabolic diseases of the adults, such as obesity, type-2 diabetes and metabolic syndromes. Even more worrying is the rising prevalence of obesity in children. It is due more to sedentariness, caused more by inactivity (television, video, games, etc.) than by overeating. Many studies have shown that regular physical activities benefit various bodily functions including metabolism. After dealing with the major benefits of physical exercise on some adult metabolic disorders, we focus on the prime role played by physical activity in combating the public health problem of childhood obesity.

  2. Sleep and metabolic function.

    Morselli, Lisa L; Guyon, Aurore; Spiegel, Karine

    2012-01-01

    Evidence for the role of sleep on metabolic and endocrine function has been reported more than four decades ago. In the past 30 years, the prevalence of obesity and diabetes has greatly increased in industrialized countries, and self-imposed sleep curtailment, now very common, is starting to be recognized as a contributing factor, alongside with increased caloric intake and decreased physical activity. Furthermore, obstructive sleep apnea, a chronic condition characterized by recurrent upper airway obstruction leading to intermittent hypoxemia and sleep fragmentation, has also become highly prevalent as a consequence of the epidemic of obesity and has been shown to contribute, in a vicious circle, to the metabolic disturbances observed in obese patients. In this article, we summarize the current data supporting the role of sleep in the regulation of glucose homeostasis and the hormones involved in the regulation of appetite. We also review the results of the epidemiologic and laboratory studies that investigated the impact of sleep duration and quality on the risk of developing diabetes and obesity, as well as the mechanisms underlying this increased risk. Finally, we discuss how obstructive sleep apnea affects glucose metabolism and the beneficial impact of its treatment, the continuous positive airway pressure. In conclusion, the data available in the literature highlight the importance of getting enough good sleep for metabolic health.

  3. Endocrine and metabolic emergencies in children: hypocalcemia, hypoglycemia, adrenal insufficiency, and metabolic acidosis including diabetic ketoacidosis

    Se Young Kim

    2015-12-01

    Full Text Available It is important to fast diagnosis and management of the pediatric patients of the endocrine metabolic emergencies because the signs and symptoms of these disorders are nonspecific. Delayed diagnosis and treatment may lead to serious consequences of the pediatric patients, for example, cerebral dysfunction leading to coma or death of the patients with hypoglycemia, hypocalcemia, adrenal insufficiency, or diabetic ketoacidosis. The index of suspicion of the endocrine metabolic emergencies should be preceded prior to the starting nonspecific treatment. Importantly, proper diagnosis depends on the collection of blood and urine specimen before nonspecific therapy (intravenous hydration, electrolytes, glucose or calcium injection. At the same time, the taking of precise history and searching for pathognomonic physical findings should be performed. This review was described for fast diagnosis and proper management of hypoglycemic emergencies, hypocalcemia, adrenal insufficiency, and metabolic acidosis including diabetic ketoacidosis.

  4. Metabolic Interplay between Peroxisomes and Other Subcellular Organelles Including Mitochondria and the Endoplasmic Reticulum

    Wanders, Ronald J. A.; Waterham, Hans R.; Ferdinandusse, Sacha

    2016-01-01

    Peroxisomes are unique subcellular organelles which play an indispensable role in several key metabolic pathways which include: (1.) etherphospholipid biosynthesis; (2.) fatty acid beta-oxidation; (3.) bile acid synthesis; (4.) docosahexaenoic acid (DHA) synthesis; (5.) fatty acid alpha-oxidation; (6.) glyoxylate metabolism; (7.) amino acid degradation, and (8.) ROS/RNS metabolism. The importance of peroxisomes for human health and development is exemplified by the existence of a large number of inborn errors of peroxisome metabolism in which there is an impairment in one or more of the metabolic functions of peroxisomes. Although the clinical signs and symptoms of affected patients differ depending upon the enzyme which is deficient and the extent of the deficiency, the disorders involved are usually (very) severe diseases with neurological dysfunction and early death in many of them. With respect to the role of peroxisomes in metabolism it is clear that peroxisomes are dependent on the functional interplay with other subcellular organelles to sustain their role in metabolism. Indeed, whereas mitochondria can oxidize fatty acids all the way to CO2 and H2O, peroxisomes are only able to chain-shorten fatty acids and the end products of peroxisomal beta-oxidation need to be shuttled to mitochondria for full oxidation to CO2 and H2O. Furthermore, NADH is generated during beta-oxidation in peroxisomes and beta-oxidation can only continue if peroxisomes are equipped with a mechanism to reoxidize NADH back to NAD+, which is now known to be mediated by specific NAD(H)-redox shuttles. In this paper we describe the current state of knowledge about the functional interplay between peroxisomes and other subcellular compartments notably the mitochondria and endoplasmic reticulum for each of the metabolic pathways in which peroxisomes are involved. PMID:26858947

  5. Prevention of metabolic diseases: fruits (including fruit sugars) vs. vegetables.

    Kuzma, Jessica N; Schmidt, Kelsey A; Kratz, Mario

    2017-07-01

    To discuss recent evidence from observational and intervention studies on the relationship between fruit and vegetable (F&V) consumption and metabolic disease. Observational studies have consistently demonstrated a modest inverse association between the intake of fruit and leafy green vegetables, but not total vegetables, and biomarkers of metabolic disease as well as incident type 2 diabetes mellitus. This is in contrast to limited evidence from recently published randomized controlled dietary intervention trials, which - in sum - suggests little to no impact of increased F&V consumption on biomarkers of metabolic disease. Evidence from observational studies that fruit and leafy green vegetable intake is associated with lower type 2 diabetes risk and better metabolic health could not be confirmed by dietary intervention trials. It is unclear whether this discrepancy is because of limitations inherent in observational studies (e.g., subjective dietary assessment methods, residual confounding) or due to limitations in the few available intervention studies (e.g., short duration of follow-up, interventions combining whole fruit and fruit juice, or lack of compliance). Future studies that attempt to address these limitations are needed to provide more conclusive insight into the impact of F&V consumption on metabolic health.

  6. Distal radioulnar joint: functional anatomy, including pathomechanics.

    Haugstvedt, J R; Langer, M F; Berger, R A

    2017-05-01

    The distal radioulnar joint allows the human to rotate the forearm to place the hand in a desired position to perform different tasks, without interfering with the grasping function of the hand. The ulna is the stable part of the forearm around which the radius rotates; the stability of the distal radioulnar joint is provided by the interaction between ligaments, muscles and bones. The stabilizing structures are the triangular fibrocartilage complex, the ulnocarpal ligament complex, the extensor carpi ulnaris tendon and tendon sheath, the pronator quadratus, the interosseous membrane and ligament, the bone itself and the joint capsule. The purpose of this review article is to present and illustrate the current understanding of the functional anatomy and pathomechanics of this joint.

  7. 2011 Plant Lipids: Structure, Metabolism, & Function Gordon Research Conference

    Christopher Benning

    2011-02-04

    This is the second Gordon Research Conference on 'Plant Lipids: Structure, Metabolism & Function'. It covers current topics in lipid structure, metabolism and function in eukaryotic photosynthetic organisms including seed plants, algae, mosses and ferns. Work in photosynthetic bacteria is considered as well as it serves the understanding of specific aspects of lipid metabolism in plants. Breakthroughs are discussed in research on plant lipids as diverse as glycerolipids, sphingolipids, lipids of the cell surface, isoprenoids, fatty acids and their derivatives. The program covers nine concepts at the forefront of research under which afore mentioned plant lipid classes are discussed. The goal is to integrate areas such as lipid signaling, basic lipid metabolism, membrane function, lipid analysis, and lipid engineering to achieve a high level of stimulating interaction among diverse researchers with interests in plant lipids. One Emphasis is on the dynamics and regulation of lipid metabolism during plant cell development and in response to environmental factors.

  8. AMPK in skeletal muscle function and metabolism

    Kjøbsted, Rasmus; Hingst, Janne Rasmuss; Fentz, Joachim

    2018-01-01

    Skeletal muscle possesses a remarkable ability to adapt to various physiologic conditions. AMPK is a sensor of intracellular energy status that maintains energy stores by fine-tuning anabolic and catabolic pathways. AMPK's role as an energy sensor is particularly critical in tissues displaying...... highly changeable energy turnover. Due to the drastic changes in energy demand that occur between the resting and exercising state, skeletal muscle is one such tissue. Here, we review the complex regulation of AMPK in skeletal muscle and its consequences on metabolism (e.g., substrate uptake, oxidation......, and storage as well as mitochondrial function of skeletal muscle fibers). We focus on the role of AMPK in skeletal muscle during exercise and in exercise recovery. We also address adaptations to exercise training, including skeletal muscle plasticity, highlighting novel concepts and future perspectives...

  9. Cardiorenal metabolic syndrome in the African diaspora: rationale for including chronic kidney disease in the metabolic syndrome definition.

    Lea, Janice P; Greene, Eddie L; Nicholas, Susanne B; Agodoa, Lawrence; Norris, Keith C

    2009-01-01

    Chronic kidney disease (CKD) is more likely to progress to end-stage renal disease (ESRD) in African Americans while the reasons for this are unclear. The metabolic syndrome is a risk factor for the development of diabetes, cardiovascular disease, and has been recently linked to incident CKD. Historically, fewer African Americans meet criteria for the definition of metabolic syndrome, despite having higher rates of cardiovascular mortality than Caucasians. The presence of microalbuminuria portends increased cardiovascular risks and has been shown to cluster with the metabolic syndrome. We recently reported that proteinuria is a predictor of CKD progression in African American hypertensives with metabolic syndrome. In this review we explore the potential value of including CKD markers--microalbuminuria/proteinuria or low glomerular filtration rate (GFR)-in refining the cluster of factors defined as metabolic syndrome, ie, "cardiorenal metabolic syndrome."

  10. Executive functions in persons with metabolic syndrome

    Subotić Tatjana

    2016-01-01

    Full Text Available Modern man lyfestyle contributes to the increasing incidence of metabolic syndrome in the developed world. Prevalence of the metabolic syndrome in adults ranges from 20 to 25%, and it tends to increase. Each year, 3.2 million people around the world die from complications associated with this syndrome. Treatment involves cooperation of medical doctors of various specialties, but the decisive factor is patient motivation, given that the treatment requires significant lifestyle changes. Our hypothesis is that metabolic syndrome patients have reduced ability to plan, convert plan into action and effectively implement planned activities, showing signs of dysexecutive syndrome. The term executive functions comes from the English word 'executive', which also means the controlling, in neuropsychology reserved for high-level abilities that influence more basic abilities such as attention, perception, memory, thinking and speaking. The main objective of this study was to determine characteristics of executive functioning in patients with metabolic syndrome. The sample consisted of 61 subjects of both sexes, aged 20 to 60 years, divided into two groups - those with a diagnosis of metabolic syndrome and those without this diagnosis. The results suggest that people with metabolic syndrome showed significantly poorer performance in almost all indicators of executive functions, represented by Wisconsin Card Sorting Test (Wisconsin Card Sorting Test variables.

  11. Insulin Action in Brain Regulates Systemic Metabolism and Brain Function

    Kleinridders, Andr?; Ferris, Heather A.; Cai, Weikang; Kahn, C. Ronald

    2014-01-01

    Insulin receptors, as well as IGF-1 receptors and their postreceptor signaling partners, are distributed throughout the brain. Insulin acts on these receptors to modulate peripheral metabolism, including regulation of appetite, reproductive function, body temperature, white fat mass, hepatic glucose output, and response to hypoglycemia. Insulin signaling also modulates neurotransmitter channel activity, brain cholesterol synthesis, and mitochondrial function. Disruption of insulin action in t...

  12. Microalgal Metabolic Network Model Refinement through High-Throughput Functional Metabolic Profiling

    Chaiboonchoe, Amphun; Dohai, Bushra Saeed; Cai, Hong; Nelson, David R.; Jijakli, Kenan; Salehi-Ashtiani, Kourosh

    2014-01-01

    Metabolic modeling provides the means to define metabolic processes at a systems level; however, genome-scale metabolic models often remain incomplete in their description of metabolic networks and may include reactions that are experimentally unverified. This shortcoming is exacerbated in reconstructed models of newly isolated algal species, as there may be little to no biochemical evidence available for the metabolism of such isolates. The phenotype microarray (PM) technology (Biolog, Hayward, CA, USA) provides an efficient, high-throughput method to functionally define cellular metabolic activities in response to a large array of entry metabolites. The platform can experimentally verify many of the unverified reactions in a network model as well as identify missing or new reactions in the reconstructed metabolic model. The PM technology has been used for metabolic phenotyping of non-photosynthetic bacteria and fungi, but it has not been reported for the phenotyping of microalgae. Here, we introduce the use of PM assays in a systematic way to the study of microalgae, applying it specifically to the green microalgal model species Chlamydomonas reinhardtii. The results obtained in this study validate a number of existing annotated metabolic reactions and identify a number of novel and unexpected metabolites. The obtained information was used to expand and refine the existing COBRA-based C. reinhardtii metabolic network model iRC1080. Over 254 reactions were added to the network, and the effects of these additions on flux distribution within the network are described. The novel reactions include the support of metabolism by a number of d-amino acids, l-dipeptides, and l-tripeptides as nitrogen sources, as well as support of cellular respiration by cysteamine-S-phosphate as a phosphorus source. The protocol developed here can be used as a foundation to functionally profile other microalgae such as known microalgae mutants and novel isolates.

  13. Microalgal Metabolic Network Model Refinement through High-Throughput Functional Metabolic Profiling

    Chaiboonchoe, Amphun; Dohai, Bushra Saeed; Cai, Hong; Nelson, David R. [Division of Science and Math, New York University Abu Dhabi, Abu Dhabi (United Arab Emirates); Center for Genomics and Systems Biology (CGSB), New York University Abu Dhabi Institute, Abu Dhabi (United Arab Emirates); Jijakli, Kenan [Division of Science and Math, New York University Abu Dhabi, Abu Dhabi (United Arab Emirates); Center for Genomics and Systems Biology (CGSB), New York University Abu Dhabi Institute, Abu Dhabi (United Arab Emirates); Engineering Division, Biofinery, Manhattan, KS (United States); Salehi-Ashtiani, Kourosh, E-mail: ksa3@nyu.edu [Division of Science and Math, New York University Abu Dhabi, Abu Dhabi (United Arab Emirates); Center for Genomics and Systems Biology (CGSB), New York University Abu Dhabi Institute, Abu Dhabi (United Arab Emirates)

    2014-12-10

    Metabolic modeling provides the means to define metabolic processes at a systems level; however, genome-scale metabolic models often remain incomplete in their description of metabolic networks and may include reactions that are experimentally unverified. This shortcoming is exacerbated in reconstructed models of newly isolated algal species, as there may be little to no biochemical evidence available for the metabolism of such isolates. The phenotype microarray (PM) technology (Biolog, Hayward, CA, USA) provides an efficient, high-throughput method to functionally define cellular metabolic activities in response to a large array of entry metabolites. The platform can experimentally verify many of the unverified reactions in a network model as well as identify missing or new reactions in the reconstructed metabolic model. The PM technology has been used for metabolic phenotyping of non-photosynthetic bacteria and fungi, but it has not been reported for the phenotyping of microalgae. Here, we introduce the use of PM assays in a systematic way to the study of microalgae, applying it specifically to the green microalgal model species Chlamydomonas reinhardtii. The results obtained in this study validate a number of existing annotated metabolic reactions and identify a number of novel and unexpected metabolites. The obtained information was used to expand and refine the existing COBRA-based C. reinhardtii metabolic network model iRC1080. Over 254 reactions were added to the network, and the effects of these additions on flux distribution within the network are described. The novel reactions include the support of metabolism by a number of d-amino acids, l-dipeptides, and l-tripeptides as nitrogen sources, as well as support of cellular respiration by cysteamine-S-phosphate as a phosphorus source. The protocol developed here can be used as a foundation to functionally profile other microalgae such as known microalgae mutants and novel isolates.

  14. Energy Metabolism of the Brain, Including the Cooperation between Astrocytes and Neurons, Especially in the Context of Glycogen Metabolism.

    Falkowska, Anna; Gutowska, Izabela; Goschorska, Marta; Nowacki, Przemysław; Chlubek, Dariusz; Baranowska-Bosiacka, Irena

    2015-10-29

    Glycogen metabolism has important implications for the functioning of the brain, especially the cooperation between astrocytes and neurons. According to various research data, in a glycogen deficiency (for example during hypoglycemia) glycogen supplies are used to generate lactate, which is then transported to neighboring neurons. Likewise, during periods of intense activity of the nervous system, when the energy demand exceeds supply, astrocyte glycogen is immediately converted to lactate, some of which is transported to the neurons. Thus, glycogen from astrocytes functions as a kind of protection against hypoglycemia, ensuring preservation of neuronal function. The neuroprotective effect of lactate during hypoglycemia or cerebral ischemia has been reported in literature. This review goes on to emphasize that while neurons and astrocytes differ in metabolic profile, they interact to form a common metabolic cooperation.

  15. Brain glucose metabolism during hypoglycemia in type 1 diabetes: insights from functional and metabolic neuroimaging studies.

    Rooijackers, Hanne M M; Wiegers, Evita C; Tack, Cees J; van der Graaf, Marinette; de Galan, Bastiaan E

    2016-02-01

    Hypoglycemia is the most frequent complication of insulin therapy in patients with type 1 diabetes. Since the brain is reliant on circulating glucose as its main source of energy, hypoglycemia poses a threat for normal brain function. Paradoxically, although hypoglycemia commonly induces immediate decline in cognitive function, long-lasting changes in brain structure and cognitive function are uncommon in patients with type 1 diabetes. In fact, recurrent hypoglycemia initiates a process of habituation that suppresses hormonal responses to and impairs awareness of subsequent hypoglycemia, which has been attributed to adaptations in the brain. These observations sparked great scientific interest into the brain's handling of glucose during (recurrent) hypoglycemia. Various neuroimaging techniques have been employed to study brain (glucose) metabolism, including PET, fMRI, MRS and ASL. This review discusses what is currently known about cerebral metabolism during hypoglycemia, and how findings obtained by functional and metabolic neuroimaging techniques contributed to this knowledge.

  16. Energy Metabolism of the Brain, Including the Cooperation between Astrocytes and Neurons, Especially in the Context of Glycogen Metabolism

    Falkowska, Anna; Gutowska, Izabela; Goschorska, Marta; Nowacki, Przemys?aw; Chlubek, Dariusz; Baranowska-Bosiacka, Irena

    2015-01-01

    Glycogen metabolism has important implications for the functioning of the brain, especially the cooperation between astrocytes and neurons. According to various research data, in a glycogen deficiency (for example during hypoglycemia) glycogen supplies are used to generate lactate, which is then transported to neighboring neurons. Likewise, during periods of intense activity of the nervous system, when the energy demand exceeds supply, astrocyte glycogen is immediately converted to lactate, s...

  17. Insulin action in brain regulates systemic metabolism and brain function.

    Kleinridders, André; Ferris, Heather A; Cai, Weikang; Kahn, C Ronald

    2014-07-01

    Insulin receptors, as well as IGF-1 receptors and their postreceptor signaling partners, are distributed throughout the brain. Insulin acts on these receptors to modulate peripheral metabolism, including regulation of appetite, reproductive function, body temperature, white fat mass, hepatic glucose output, and response to hypoglycemia. Insulin signaling also modulates neurotransmitter channel activity, brain cholesterol synthesis, and mitochondrial function. Disruption of insulin action in the brain leads to impairment of neuronal function and synaptogenesis. In addition, insulin signaling modulates phosphorylation of tau protein, an early component in the development of Alzheimer disease. Thus, alterations in insulin action in the brain can contribute to metabolic syndrome, and the development of mood disorders and neurodegenerative diseases. © 2014 by the American Diabetes Association.

  18. EFFECT OF DANCE EXERCISE ON COGNITIVE FUNCTION IN ELDERLY PATIENTS WITH METABOLIC SYNDROME: A PILOT STUDY

    Sang-Wook Song; Seo-Jin Park; Jung-hyoun Cho; Sung-Goo Kang; Hyun-Kook Lim; Yu-Bae Ahn; Minjeong Kim; Se-Hong Kim

    2011-01-01

    Metabolic syndrome is associated with an increased risk of cognitive impairment. The purpose of this prospective pilot study was to examine the effects of dance exercise on cognitive function in elderly patients with metabolic syndrome. The participants included 38 elderly metabolic syndrome patients with normal cognitive function (26 exercise group and 12 control group). The exercise group performed dance exercise twice a week for 6 months. Cognitive function was assessed in all participants...

  19. Nuclear magnetic resonance studies of epithelial metabolism and function

    Balaban, R.S.

    1982-01-01

    Nuclear magnetic resonance (NMR) is a noninvasive technique for studying cellular metabolism and function. In this review the general applications and advantages of NMR will be discussed with specific reference to epithelial tissues. Phosphorus NMR investigations have been performed on epithelial tissues in vivo and in vitro; however, other detectable nuclei have not been utilized to date. Several new applications of phosphorus NMR to epithelial tissues are also discussed, including studies on isolated renal tubules and sheet epithelia

  20. Dancing for Healthy Aging: Functional and Metabolic Perspectives.

    Rodrigues-Krause, Josianne; Krause, Mauricio; Reischak-Oliveira, Alvaro

    2018-02-10

    ); (3) aerobic dance with no partner required, which mixes aerobic moves with dance moves; (4) dance therapies, whichare special dance programs including emotional and physical aspects; and (5) classical dances, which are dances with a unique tradition and technique, such as ballet or jazz dance. Outcome Measures • Studies needed to have evaluated functional and/or metabolic outcomes. Functional outcomes included (1) static and/or dynamic balance, (2) gait ability, (3) upper and/or lower muscle strength or power, (4) cardiorespiratory fitness, (5) flexibility, (6) risk of falls, and (7) quality of life. Metabolic outcomes included (1) lipid and glycemic profile; (2) systolic and diastolic blood pressure; (3) body composition; and (4) other specific cardiovascular risk factors or inflammatory or oxidative stress markers. Results • The research team retrieved 1042 articles, with 88 full texts assessed for eligibility, and 50 articles included in the analysis. Of the analyzed studies, 22 were RCTs evaluating dancing vs controls, and 3 were RCTs evaluating dancing vs other exercise. Regarding the participants of the reviewed studies: (1) 31 evaluated healthy individuals, (2) 7 evaluated patients suffering from Parkinson's disease, (3) 4 evaluated postmenopausal women, (4) 2 evaluated obese women, (5) 2 evaluated patients with chronic heart failure, (6) 1 evaluated frail older adults, (7) 1 evaluated individuals with visual impairments, (8) 1 evaluated persons with metabolic syndrome, and (9) 1 evaluated individuals with severe pain in the lower extremities. Regarding the interventions, most interventions were 12 wk long, 3 ×/wk, for 60 min each session. The dance styles most used were ballroom and cultural dances. Regarding the outcomes, functional and metabolic benefits were described in most of the included studies. Balance was the functional outcome most often assessed. Conclusions • Any dance style can induce positive functional adaptations in older adults

  1. Development, regulation, metabolism and function of bone marrow adipose tissues.

    Li, Ziru; Hardij, Julie; Bagchi, Devika P; Scheller, Erica L; MacDougald, Ormond A

    2018-05-01

    Most adipocytes exist in discrete depots throughout the body, notably in well-defined white and brown adipose tissues. However, adipocytes also reside within specialized niches, of which the most abundant is within bone marrow. Whereas bone marrow adipose tissue (BMAT) shares many properties in common with white adipose tissue, the distinct functions of BMAT are reflected by its development, regulation, protein secretion, and lipid composition. In addition to its potential role as a local energy reservoir, BMAT also secretes proteins, including adiponectin, RANK ligand, dipeptidyl peptidase-4, and stem cell factor, which contribute to local marrow niche functions and which may also influence global metabolism. The characteristics of BMAT are also distinct depending on whether marrow adipocytes are contained within yellow or red marrow, as these can be thought of as 'constitutive' and 'regulated', respectively. The rBMAT for instance can be expanded or depleted by myriad factors, including age, nutrition, endocrine status and pharmaceuticals. Herein we review the site specificity, age-related development, regulation and metabolic characteristics of BMAT under various metabolic conditions, including the functional interactions with bone and hematopoietic cells. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Enduring effects of severe developmental adversity, including nutritional deprivation, on cortisol metabolism in aging Holocaust survivors.

    Yehuda, Rachel; Bierer, Linda M; Andrew, Ruth; Schmeidler, James; Seckl, Jonathan R

    2009-06-01

    In animal models, early life exposure to major environmental challenges such as malnutrition and stress results in persisting cardiometabolic, neuroendocrine and affective effects. While such effects have been associated with pathogenesis, the widespread occurrence of 'developmental programming' suggests it has adaptive function. Glucocorticoids may mediate 'programming' and their metabolism is known to be affected by early life events in rodents. To examine these relationships in humans, cortisol metabolism and cardiometabolic disease manifestations were examined in Holocaust survivors in relation to age at exposure and affective dysfunction, notably lifetime posttraumatic stress disorder (PTSD). Fifty-one Holocaust survivors and 22 controls without Axis I disorder collected 24-h urine samples and were evaluated for psychiatric disorders and cardiometabolic diagnoses. Corticosteroids and their metabolites were assayed by gas chromatography-mass spectroscopy (GC-MS); cortisol was also measured by radioimmunoassay (RIA). Holocaust survivors showed reduced cortisol by RIA, and decreased levels of 5alpha-tetrahydrocortisol (5alpha-THF) and total glucocorticoid production by GC-MS. The latter was associated with lower cortisol metabolism by 5alpha-reductase and 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type-2. The greatest decrements were associated with earliest age of Holocaust exposure and less severe PTSD symptomatology. Cardiometabolic manifestations were associated with decreased 11beta-HSD-2 activity. In controls, 5alpha-reductase was positively associated with trauma-related symptoms (i.e., to traumatic exposures unrelated to the Holocaust). Extreme malnutrition and related stress during development is associated with long-lived alterations in specific pathways of glucocorticoid metabolism. These effects may be adaptive and link with lower risks of cardiometabolic and stress-related disorders in later life.

  3. Metabolic and functional connectivity changes in mal de debarquement syndrome.

    Yoon-Hee Cha

    Full Text Available Individuals with mal de debarquement syndrome (MdDS experience a chronic illusion of self-motion triggered by prolonged exposure to passive motion, such as from sea or air travel. The experience is one of rocking dizziness similar to when the individual was originally on the motion trigger such as a boat or airplane. MdDS represents a prolonged version of a normal phenomenon familiar to most individuals but which persists for months or years in others. It represents a natural example of the neuroplasticity of motion adaptation. However, the localization of where that motion adaptation occurs is unknown. Our goal was to localize metabolic and functional connectivity changes associated with persistent MdDS.Twenty subjects with MdDS lasting a median duration of 17.5 months were compared to 20 normal controls with (18F FDG PET and resting state fMRI. Resting state metabolism and functional connectivity were calculated using age, grey matter volume, and mood and anxiety scores as nuisance covariates.MdDS subjects showed increased metabolism in the left entorhinal cortex and amygdala (z>3.3. Areas of relative hypometabolism included the left superior medial gyrus, left middle frontal gyrus, right amygdala, right insula, and clusters in the left superior, middle, and inferior temporal gyri. MdDS subjects showed increased connectivity between the entorhinal cortex/amygdala cluster and posterior visual and vestibular processing areas including middle temporal gyrus, motion sensitive area MT/V5, superior parietal lobule, and primary visual cortex, while showing decreased connectivity to multiple prefrontal areas.These data show an association between resting state metabolic activity and functional connectivity between the entorhinal cortex and amygdala in a human disorder of abnormal motion perception. We propose a model for how these biological substrates can allow a limited period of motion exposure to lead to chronic perceptions of self-motion.

  4. Changes in bone mineral metabolism parameters, including FGF23, after discontinuing cinacalcet at kidney transplantation.

    Barros, Xoana; Fuster, David; Paschoalin, Raphael; Oppenheimer, Federico; Rubello, Domenico; Perlaza, Pilar; Pons, Francesca; Torregrosa, Jose V

    2015-05-01

    Little is known about the effects of the administration of cinacalcet in dialytic patients who are scheduled for kidney transplantation, and in particular about the changes in FGF23 and other mineral metabolism parameters after surgery compared with recipients not on cinacalcet at kidney transplantation. We performed a prospective observational cohort study with recruitment of consecutive kidney transplant recipients at our institution. Patients were classified according to whether they were under treatment with cinacalcet before transplantation. Bone mineral metabolism parameters, including C-terminal FGF23, were measured at baseline, on day 15, and at 1, 3, and 6 months after transplantation. In previously cinacalcet-treated patients, cinacalcet therapy was discontinued on the day of surgery and was not restarted after transplantation. A total of 48 kidney transplant recipients, 20 on cinacalcet at surgery and 28 cinacalcet non-treated patients, completed the follow-up. Serum phosphate declined significantly in the first 15 days after transplantation with no differences between the two groups, whereas cinacalcet-treated patients showed higher FGF23 levels, although not significant. After transplantation, PTH and serum calcium were significantly higher in cinacalcet-treated patients. We conclude that patients receiving cinacalcet on dialysis presented similar serum phosphate levels but higher PTH and serum calcium levels during the initial six months after kidney transplantation than cinacalcet non-treated patients. The group previously treated with cinacalcet before transplantation showed higher FGF23 levels without significant differences, so further studies should investigate its relevance in the management of these patients.

  5. Accessing Autonomic Function Can Early Screen Metabolic Syndrome

    Dai, Meng; Li, Mian; Yang, Zhi; Xu, Min; Xu, Yu; Lu, Jieli; Chen, Yuhong; Liu, Jianmin; Ning, Guang; Bi, Yufang

    2012-01-01

    Background Clinical diagnosis of the metabolic syndrome is time-consuming and invasive. Convenient instruments that do not require laboratory or physical investigation would be useful in early screening individuals at high risk of metabolic syndrome. Examination of the autonomic function can be taken as a directly reference and screening indicator for predicting metabolic syndrome. Methodology and Principal Findings The EZSCAN test, as an efficient and noninvasive technology, can access autonomic function through measuring electrochemical skin conductance. In this study, we used EZSCAN value to evaluate autonomic function and to detect metabolic syndrome in 5,887 participants aged 40 years or older. The EZSCAN test diagnostic accuracy was analyzed by receiver operating characteristic curves. Among the 5,815 participants in the final analysis, 2,541 were diagnosed as metabolic syndrome and the overall prevalence was 43.7%. Prevalence of the metabolic syndrome increased with the elevated EZSCAN risk level (p for trend metabolic syndrome components (p for trend metabolic syndrome after the multiple adjustments. The area under the curve of the EZSCAN test was 0.62 (95% confidence interval [CI], 0.61–0.64) for predicting metabolic syndrome. The optimal operating point for the EZSCAN value to detect a high risk of prevalent metabolic syndrome was 30 in this study, while the sensitivity and specificity were 71.2% and 46.7%, respectively. Conclusions and Significance In conclusion, although less sensitive and accurate when compared with the clinical definition of metabolic syndrome, we found that the EZSCAN test is a good and simple screening technique for early predicting metabolic syndrome. PMID:22916265

  6. Accessing autonomic function can early screen metabolic syndrome.

    Kan Sun

    Full Text Available BACKGROUND: Clinical diagnosis of the metabolic syndrome is time-consuming and invasive. Convenient instruments that do not require laboratory or physical investigation would be useful in early screening individuals at high risk of metabolic syndrome. Examination of the autonomic function can be taken as a directly reference and screening indicator for predicting metabolic syndrome. METHODOLOGY AND PRINCIPAL FINDINGS: The EZSCAN test, as an efficient and noninvasive technology, can access autonomic function through measuring electrochemical skin conductance. In this study, we used EZSCAN value to evaluate autonomic function and to detect metabolic syndrome in 5,887 participants aged 40 years or older. The EZSCAN test diagnostic accuracy was analyzed by receiver operating characteristic curves. Among the 5,815 participants in the final analysis, 2,541 were diagnosed as metabolic syndrome and the overall prevalence was 43.7%. Prevalence of the metabolic syndrome increased with the elevated EZSCAN risk level (p for trend <0.0001. Moreover, EZSCAN value was associated with an increase in the number of metabolic syndrome components (p for trend <0.0001. Compared with the no risk group (EZSCAN value 0-24, participants at the high risk group (EZSCAN value: 50-100 had a 2.35 fold increased risk of prevalent metabolic syndrome after the multiple adjustments. The area under the curve of the EZSCAN test was 0.62 (95% confidence interval [CI], 0.61-0.64 for predicting metabolic syndrome. The optimal operating point for the EZSCAN value to detect a high risk of prevalent metabolic syndrome was 30 in this study, while the sensitivity and specificity were 71.2% and 46.7%, respectively. CONCLUSIONS AND SIGNIFICANCE: In conclusion, although less sensitive and accurate when compared with the clinical definition of metabolic syndrome, we found that the EZSCAN test is a good and simple screening technique for early predicting metabolic syndrome.

  7. A Cellular Perspective on Brain Energy Metabolism and Functional Imaging

    Magistretti, Pierre J.

    2015-05-01

    The energy demands of the brain are high: they account for at least 20% of the body\\'s energy consumption. Evolutionary studies indicate that the emergence of higher cognitive functions in humans is associated with an increased glucose utilization and expression of energy metabolism genes. Functional brain imaging techniques such as fMRI and PET, which are widely used in human neuroscience studies, detect signals that monitor energy delivery and use in register with neuronal activity. Recent technological advances in metabolic studies with cellular resolution have afforded decisive insights into the understanding of the cellular and molecular bases of the coupling between neuronal activity and energy metabolism and pointat a key role of neuron-astrocyte metabolic interactions. This article reviews some of the most salient features emerging from recent studies and aims at providing an integration of brain energy metabolism across resolution scales. © 2015 Elsevier Inc.

  8. Conversion of KEGG metabolic pathways to SBGN maps including automatic layout.

    Czauderna, Tobias; Wybrow, Michael; Marriott, Kim; Schreiber, Falk

    2013-08-16

    Biologists make frequent use of databases containing large and complex biological networks. One popular database is the Kyoto Encyclopedia of Genes and Genomes (KEGG) which uses its own graphical representation and manual layout for pathways. While some general drawing conventions exist for biological networks, arbitrary graphical representations are very common. Recently, a new standard has been established for displaying biological processes, the Systems Biology Graphical Notation (SBGN), which aims to unify the look of such maps. Ideally, online repositories such as KEGG would automatically provide networks in a variety of notations including SBGN. Unfortunately, this is non-trivial, since converting between notations may add, remove or otherwise alter map elements so that the existing layout cannot be simply reused. Here we describe a methodology for automatic translation of KEGG metabolic pathways into the SBGN format. We infer important properties of the KEGG layout and treat these as layout constraints that are maintained during the conversion to SBGN maps. This allows for the drawing and layout conventions of SBGN to be followed while creating maps that are still recognizably the original KEGG pathways. This article details the steps in this process and provides examples of the final result.

  9. The Functions of Metamorphic Metallothioneins in Zinc and Copper Metabolism.

    Krężel, Artur; Maret, Wolfgang

    2017-06-09

    Recent discoveries in zinc biology provide a new platform for discussing the primary physiological functions of mammalian metallothioneins (MTs) and their exquisite zinc-dependent regulation. It is now understood that the control of cellular zinc homeostasis includes buffering of Zn 2+ ions at picomolar concentrations, extensive subcellular re-distribution of Zn 2+ , the loading of exocytotic vesicles with zinc species, and the control of Zn 2+ ion signalling. In parallel, characteristic features of human MTs became known: their graded affinities for Zn 2+ and the redox activity of their thiolate coordination environments. Unlike the single species that structural models of mammalian MTs describe with a set of seven divalent or eight to twelve monovalent metal ions, MTs are metamorphic. In vivo, they exist as many species differing in redox state and load with different metal ions. The functions of mammalian MTs should no longer be considered elusive or enigmatic because it is now evident that the reactivity and coordination dynamics of MTs with Zn 2+ and Cu⁺ match the biological requirements for controlling-binding and delivering-these cellular metal ions, thus completing a 60-year search for their functions. MT represents a unique biological principle for buffering the most competitive essential metal ions Zn 2+ and Cu⁺. How this knowledge translates to the function of other families of MTs awaits further insights into the specifics of how their properties relate to zinc and copper metabolism in other organisms.

  10. The Functions of Metamorphic Metallothioneins in Zinc and Copper Metabolism

    Artur Krężel

    2017-06-01

    Full Text Available Recent discoveries in zinc biology provide a new platform for discussing the primary physiological functions of mammalian metallothioneins (MTs and their exquisite zinc-dependent regulation. It is now understood that the control of cellular zinc homeostasis includes buffering of Zn2+ ions at picomolar concentrations, extensive subcellular re-distribution of Zn2+, the loading of exocytotic vesicles with zinc species, and the control of Zn2+ ion signalling. In parallel, characteristic features of human MTs became known: their graded affinities for Zn2+ and the redox activity of their thiolate coordination environments. Unlike the single species that structural models of mammalian MTs describe with a set of seven divalent or eight to twelve monovalent metal ions, MTs are metamorphic. In vivo, they exist as many species differing in redox state and load with different metal ions. The functions of mammalian MTs should no longer be considered elusive or enigmatic because it is now evident that the reactivity and coordination dynamics of MTs with Zn2+ and Cu+ match the biological requirements for controlling—binding and delivering—these cellular metal ions, thus completing a 60-year search for their functions. MT represents a unique biological principle for buffering the most competitive essential metal ions Zn2+ and Cu+. How this knowledge translates to the function of other families of MTs awaits further insights into the specifics of how their properties relate to zinc and copper metabolism in other organisms.

  11. Metabolic Profiling of Impaired Cognitive Function in Patients Receiving Dialysis

    Kurella Tamura, Manjula; Chertow, Glenn M.; Depner, Thomas A.; Nissenson, Allen R.; Schiller, Brigitte; Mehta, Ravindra L.; Liu, Sai; Sirich, Tammy L.

    2016-01-01

    Retention of uremic metabolites is a proposed cause of cognitive impairment in patients with ESRD. We used metabolic profiling to identify and validate uremic metabolites associated with impairment in executive function in two cohorts of patients receiving maintenance dialysis. We performed metabolic profiling using liquid chromatography/mass spectrometry applied to predialysis plasma samples from a discovery cohort of 141 patients and an independent replication cohort of 180 patients partici...

  12. Vitamin D metabolism, sex hormones, and male reproductive function

    Blomberg Jensen, Martin

    2012-01-01

    The spectrum of vitamin D (VD)-mediated effects has expanded in recent years, and VD is now recognized as a versatile signaling molecule rather than being solely a regulator of bone health and calcium homeostasis. One of the recently identified target areas of VD is male reproductive function...... is the main VD target in the testis and to what extent VD is important for sex hormone production and function of spermatozoa. This review summarizes descriptive studies on testicular VD metabolism and spatial distribution of VDR and the VD metabolizing enzymes in the mammalian testes and discusses...

  13. Cell-selective metabolic labeling of biomolecules with bioorthogonal functionalities.

    Xie, Ran; Hong, Senlian; Chen, Xing

    2013-10-01

    Metabolic labeling of biomolecules with bioorthogonal functionalities enables visualization, enrichment, and analysis of the biomolecules of interest in their physiological environments. This versatile strategy has found utility in probing various classes of biomolecules in a broad range of biological processes. On the other hand, metabolic labeling is nonselective with respect to cell type, which imposes limitations for studies performed in complex biological systems. Herein, we review the recent methodological developments aiming to endow metabolic labeling strategies with cell-type selectivity. The cell-selective metabolic labeling strategies have emerged from protein and glycan labeling. We envision that these strategies can be readily extended to labeling of other classes of biomolecules. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Transcriptome landscape of Lactococcus lactis reveals many novel RNAs including a small regulatory RNA involved in carbon uptake and metabolism.

    van der Meulen, Sjoerd B; de Jong, Anne; Kok, Jan

    2016-01-01

    RNA sequencing has revolutionized genome-wide transcriptome analyses, and the identification of non-coding regulatory RNAs in bacteria has thus increased concurrently. Here we reveal the transcriptome map of the lactic acid bacterial paradigm Lactococcus lactis MG1363 by employing differential RNA sequencing (dRNA-seq) and a combination of manual and automated transcriptome mining. This resulted in a high-resolution genome annotation of L. lactis and the identification of 60 cis-encoded antisense RNAs (asRNAs), 186 trans-encoded putative regulatory RNAs (sRNAs) and 134 novel small ORFs. Based on the putative targets of asRNAs, a novel classification is proposed. Several transcription factor DNA binding motifs were identified in the promoter sequences of (a)sRNAs, providing insight in the interplay between lactococcal regulatory RNAs and transcription factors. The presence and lengths of 14 putative sRNAs were experimentally confirmed by differential Northern hybridization, including the abundant RNA 6S that is differentially expressed depending on the available carbon source. For another sRNA, LLMGnc_147, functional analysis revealed that it is involved in carbon uptake and metabolism. L. lactis contains 13% leaderless mRNAs (lmRNAs) that, from an analysis of overrepresentation in GO classes, seem predominantly involved in nucleotide metabolism and DNA/RNA binding. Moreover, an A-rich sequence motif immediately following the start codon was uncovered, which could provide novel insight in the translation of lmRNAs. Altogether, this first experimental genome-wide assessment of the transcriptome landscape of L. lactis and subsequent sRNA studies provide an extensive basis for the investigation of regulatory RNAs in L. lactis and related lactococcal species.

  15. Glucose metabolism regulates T cell activation, differentiation and functions

    Clovis Steve Palmer

    2015-01-01

    Full Text Available The adaptive immune system is equipped to eliminate both tumors and pathogenic microorganisms. It requires a series of complex and coordinated signals to drive the activation, proliferation and differentiation of appropriate T cell subsets. It is now established that changes in cellular activation are coupled to profound changes in cellular metabolism. In addition, emerging evidence now suggest that specific metabolic alterations associated with distinct T cell subsets may be ancillary to their differentiation and influential in their immune functions. The Warburg effect originally used to describe a phenomenon in which most cancer cells relied on aerobic glycolysis for their growth is a key process that sustain T cell activation and differentiation. Here we review how different aspects of metabolism in T cells influence their functions, focusing on the emerging role of key regulators of glucose metabolism such as HIF-1α. A thorough understanding of the role of metabolism in T cell function could provide insights into mechanisms involved in inflammatory-mediated conditions, with the potential for developing novel therapeutic approaches to treat these diseases.

  16. Vitamin D metabolism, sex hormones, and male reproductive function.

    Blomberg Jensen, Martin

    2012-08-01

    The spectrum of vitamin D (VD)-mediated effects has expanded in recent years, and VD is now recognized as a versatile signaling molecule rather than being solely a regulator of bone health and calcium homeostasis. One of the recently identified target areas of VD is male reproductive function. The VD receptor (VDR) and the VD metabolizing enzyme expression studies documented the presence of this system in the testes, mature spermatozoa, and ejaculatory tract, suggesting that both systemic and local VD metabolism may influence male reproductive function. However, it is still debated which cell is the main VD target in the testis and to what extent VD is important for sex hormone production and function of spermatozoa. This review summarizes descriptive studies on testicular VD metabolism and spatial distribution of VDR and the VD metabolizing enzymes in the mammalian testes and discusses mechanistic and association studies conducted in animals and humans. The reviewed evidence suggests some effects of VD on estrogen and testosterone biosynthesis and implicates involvement of both systemic and local VD metabolism in the regulation of male fertility potential.

  17. Systematic inference of functional phosphorylation events in yeast metabolism.

    Chen, Yu; Wang, Yonghong; Nielsen, Jens

    2017-07-01

    Protein phosphorylation is a post-translational modification that affects proteins by changing their structure and conformation in a rapid and reversible way, and it is an important mechanism for metabolic regulation in cells. Phosphoproteomics enables high-throughput identification of phosphorylation events on metabolic enzymes, but identifying functional phosphorylation events still requires more detailed biochemical characterization. Therefore, development of computational methods for investigating unknown functions of a large number of phosphorylation events identified by phosphoproteomics has received increased attention. We developed a mathematical framework that describes the relationship between phosphorylation level of a metabolic enzyme and the corresponding flux through the enzyme. Using this framework, it is possible to quantitatively estimate contribution of phosphorylation events to flux changes. We showed that phosphorylation regulation analysis, combined with a systematic workflow and correlation analysis, can be used for inference of functional phosphorylation events in steady and dynamic conditions, respectively. Using this analysis, we assigned functionality to phosphorylation events of 17 metabolic enzymes in the yeast Saccharomyces cerevisiae , among which 10 are novel. Phosphorylation regulation analysis cannot only be extended for inference of other functional post-translational modifications but also be a promising scaffold for multi-omics data integration in systems biology. Matlab codes for flux balance analysis in this study are available in Supplementary material. yhwang@ecust.edu.cn or nielsenj@chalmers.se. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  18. The measurement of the nigrostriatal dopaminergic function and glucose metabolism in patients with movement disorders

    Otsuka, Makoto; Ichiya, Yuichi; Kuwabara, Yasuo; Sasaki, Masayuki; Fukumura, Toshimitsu; Masuda, Kouji; Shima, Fumio; Kato, Motohiro [Kyushu Univ., Fukuoka (Japan). Faculty of Medicine

    1992-12-01

    The nigrostriatal dopaminergic function and glucose metabolism were evaluated in 34 patients with various movement disorders by using positron emission tomography with [sup 18]F-Dopa and [sup 18]F-FDG respectively. The [sup 18]F-Dopa uptake in the striatum (the caudate head and the putamen) decreased in patients with Parkinson's disease but was relatively unaffected in the caudate. The cerebral glucose metabolism was normal in patients with Parkinson's disease. The [sup 18]F-Dopa uptake in the striatum also decreased in cases of atypical parkinsonism and in cases of progressive supranuclear palsy, but there was no difference in the uptake between the caudate and the putamen. The glucose metabolism decreased in the cerebral hemisphere including the striatum; this finding was also different from those of Parkinson's disease. A normal [sup 18]F-Dopa uptake in the striatum with a markedly decreased striatal glucose metabolism and a mildly decreased cortical glucose metabolism was observed in cases of Huntington's disease and Wilson's disease. The [sup 18]F-Dopa uptake in the striatum increased and the glucose metabolism was normal in cases of idiopathic dystonia. Various patterns of [sup 18]F-Dopa uptake and glucose metabolism were thus observed in the various movement disorders. These results suggest that the measurements of the [sup 18]F-Dopa uptake and the cerebral glucose metabolism would be useful for the evaluation of the striatal function in various movement disorders. (author).

  19. Platelet function, anthropometric and metabolic variables in Nigerian ...

    Platelet function, anthropometric and metabolic variables in Nigerian Type 2 Diabetic patients. ... (BSA) were assessed as indices of anthropometry, fasting blood sugar (FBS), plasma cholesterol and triglycerides (TAG) were determined using standard method and platelet aggregation test was done on the whole blood.

  20. Effect of metabolic syndrome on mitsugumin 53 expression and function.

    Hanley Ma

    Full Text Available Metabolic syndrome is a cluster of risk factors, such as obesity, insulin resistance, and hyperlipidemia that increases the individual's likelihood of developing cardiovascular diseases. Patients inflicted with metabolic disorders also suffer from tissue repair defect. Mitsugumin 53 (MG53 is a protein essential to cellular membrane repair. It facilitates the nucleation of intracellular vesicles to sites of membrane disruption to create repair patches, contributing to the regenerative capacity of skeletal and cardiac muscle tissues upon injury. Since individuals suffering from metabolic syndrome possess tissue regeneration deficiency and MG53 plays a crucial role in restoring membrane integrity, we studied MG53 activity in mice models exhibiting metabolic disorders induced by a 6 month high-fat diet (HFD feeding. Western blotting showed that MG53 expression is not altered within the skeletal and cardiac muscles of mice with metabolic syndrome. Rather, we found that MG53 levels in blood circulation were actually reduced. This data directly contradicts findings presented by Song et. al that indict MG53 as a causative factor for metabolic syndrome (Nature 494, 375-379. The diminished MG53 serum level observed may contribute to the inadequate tissue repair aptitude exhibited by diabetic patients. Furthermore, immunohistochemical analyses reveal that skeletal muscle fibers of mice with metabolic disorders experience localization of subcellular MG53 around mitochondria. This clustering may represent an adaptive response to oxidative stress resulting from HFD feeding and may implicate MG53 as a guardian to protect damaged mitochondria. Therapeutic approaches that elevate MG53 expression in serum circulation may be a novel method to treat the degenerative tissue repair function of diabetic patients.

  1. The skin function: a factor of anti-metabolic syndrome

    Zhou Shi-Sheng

    2012-04-01

    Full Text Available Abstract The body’s total antioxidant capacity represents a sum of the antioxidant capacity of various tissues/organs. A decrease in the body’s antioxidant capacity may induce oxidative stress and subsequent metabolic syndrome, a clustering of risk factors for type 2 diabetes and cardiovascular disease. The skin, the largest organ of the body, is one of the major components of the body’s total antioxidant defense system, primarily through its xenobiotic/drug biotransformation system, reactive oxygen species-scavenging system, and sweat glands- and sebaceous glands-mediated excretion system. Notably, unlike other contributors, the skin contribution is variable, depending on lifestyles and ambient temperature or seasonal variations. Emerging evidence suggests that decreased skin’s antioxidant and excretory functions (e.g., due to sedentary lifestyles and low ambient temperature may increase the risk for metabolic syndrome. This review focuses on the relationship between the variability of skin-mediated detoxification and elimination of exogenous and endogenous toxic substances and the development of metabolic syndrome. The potential role of sebum secretion in lipid and cholesterol homeostasis and its impact on metabolic syndrome, and the association between skin disorders (acanthosis nigricans, acne, and burn and metabolic syndrome are also discussed.

  2. Effects of metabolic syndrome on the functional outcomes of corticosteroid injection for De Quervain tenosynovitis.

    Roh, Y H; Noh, J H; Gong, H S; Baek, G H

    2017-06-01

    Metabolic syndrome is a constellation of medical conditions that arise from insulin resistance and abnormal adipose deposition and function. In patients with metabolic syndrome and De Quervain tenosynovitis this might affect the outcome of treatment by local corticosteroid injection. A total of 64 consecutive patients with De Quervain tenosynovitis and metabolic syndrome treated with corticosteroid injection were age- and sex-matched with 64 control patients without metabolic syndrome. The response to treatment, including visual analogue scale score for pain, objective findings consistent with De Quervain tenosynovitis (tenderness at first dorsal compartment, Finkelstein test result), and Disability of the Arm, Shoulder, and Hand score were assessed at 6, 12, and 24 weeks follow-up. Treatment failure was defined as persistence of symptoms or surgical intervention. Prior to treatment, patients with metabolic syndrome had mean initial pain visual analogue scale and Disability of the Arm, Shoulder, and Hand scores similar to those in the control group. The proportion of treatment failure in the metabolic syndrome group (43%) was significantly higher than that in the control group (20%) at 6 months follow-up. The pain visual analogue scale scores in the metabolic syndrome group were higher than the scores in the control group at the 12- and 24-week follow-ups. The Disability of the Arm, Shoulder, and Hand scores of the metabolic syndrome group were higher (more severe symptoms) than those of the control group at the 12- and 24-week follow-ups. Although considerable improvements in symptom severity and hand function will likely occur in patients with metabolic syndrome, corticosteroid injection for De Quervain tenosynovitis is not as effective in these patients compared with age- and sex-matched controls in terms of functional outcomes and treatment failure. III.

  3. EFFECT OF DANCE EXERCISE ON COGNITIVE FUNCTION IN ELDERLY PATIENTS WITH METABOLIC SYNDROME: A PILOT STUDY

    Sang-Wook Song

    2011-12-01

    Full Text Available Metabolic syndrome is associated with an increased risk of cognitive impairment. The purpose of this prospective pilot study was to examine the effects of dance exercise on cognitive function in elderly patients with metabolic syndrome. The participants included 38 elderly metabolic syndrome patients with normal cognitive function (26 exercise group and 12 control group. The exercise group performed dance exercise twice a week for 6 months. Cognitive function was assessed in all participants using the Korean version of the Consortium to Establish a Registry for Alzheimer's disease (CERAD-K. Repeated-measures ANCOVA was used to assess the effect of dance exercise on cognitive function and cardiometabolic risk factors. Compared with the control group, the exercise group significantly improved in verbal fluency (p = 0.048, word list delayed recall (p = 0.038, word list recognition (p = 0.007, and total CERAD-K score (p = 0.037. However, no significance difference was found in body mass index, blood pressure, waist circumference, fasting plasma glucose, triglyceride, and HDL cholesterol between groups over the 6-month period. In the present study, six months of dance exercise improved cognitive function in older adults with metabolic syndrome. Thus, dance exercise may reduce the risk for cognitive disorders in elderly people with metabolic syndrome.

  4. Systemic Inflammation and Lung Function Impairment in Morbidly Obese Subjects with the Metabolic Syndrome

    Astrid van Huisstede

    2013-01-01

    Full Text Available Background. Obesity and asthma are associated. There is a relationship between lung function impairment and the metabolic syndrome. Whether this relationship also exists in the morbidly obese patients is still unknown. Hypothesis. Low-grade systemic inflammation associated with the metabolic syndrome causes inflammation in the lungs and, hence, lung function impairment. Methods. This is cross-sectional study of morbidly obese patients undergoing preoperative screening for bariatric surgery. Metabolic syndrome was assessed according to the revised NCEP-ATP III criteria. Results. A total of 452 patients were included. Patients with the metabolic syndrome (n=293 had significantly higher blood monocyte (mean 5.3 versus 4.9, P=0.044 and eosinophil percentages (median 1.0 versus 0.8, P=0.002, while the total leukocyte count did not differ between the groups. The FEV1/FVC ratio was significantly lower in patients with the metabolic syndrome (76.7% versus 78.2%, P=0.032. Blood eosinophils were associated with FEV1/FVC ratio (adj. B −0.113, P=0.018. Conclusion. Although the difference in FEV1/FVC ratio between the groups is relatively small, in this cross-sectional study, and its clinical relevance may be limited, these data indicate that the presence of the metabolic syndrome may influence lung function impairment, through the induction of relative eosinophilia.

  5. Retinoic Acid-Related Orphan Receptors (RORs): Regulatory Functions in Immunity, Development, Circadian Rhythm, and Metabolism

    Cook, Donald N.; Kang, Hong Soon; Jetten, Anton M.

    2015-01-01

    In this overview, we provide an update on recent progress made in understanding the mechanisms of action, physiological functions, and roles in disease of retinoic acid related orphan receptors (RORs). We are particularly focusing on their roles in the regulation of adaptive and innate immunity, brain function, retinal development, cancer, glucose and lipid metabolism, circadian rhythm, metabolic and inflammatory diseases and neuropsychiatric disorders. We also summarize the current status of ROR agonists and inverse agonists, including their regulation of ROR activity and their therapeutic potential for management of various diseases in which RORs have been implicated. PMID:26878025

  6. Retinoic Acid-Related Orphan Receptors (RORs: Regulatory Functions in Immunity, Development, Circadian Rhythm, and Metabolism

    Donald N. Cook

    2015-12-01

    Full Text Available In this overview, we provide an update on recent progress made in understanding the mechanisms of action, physiological functions, and roles in disease of retinoic acid related orphan receptors (RORs. We are particularly focusing on their roles in the regulation of adaptive and innate immunity, brain function, retinal development, cancer, glucose and lipid metabolism, circadian rhythm, metabolic and inflammatory diseases and neuropsychiatric disorders. We also summarize the current status of ROR agonists and inverse agonists, including their regulation of ROR activity and their therapeutic potential for management of various diseases in which RORs have been implicated.

  7. Metabolism of murine TH 17 cells: Impact on cell fate and function.

    Wang, Ran; Solt, Laura A

    2016-04-01

    An effective adaptive immune response relies on the ability of lymphocytes to rapidly act upon a variety of insults. In T lymphocytes, this response includes cell growth, clonal expansion, differentiation, and cytokine production, all of which place a significant energy burden on the cell. Recent evidence shows that T-cell metabolic reprogramming is an essential component of the adaptive immune response and specific metabolic pathways dictate T-cell fate decisions, including the development of TH 17 versus T regulatory (Treg) cells. TH 17 cells have garnered significant attention due to their roles in the pathology of immune-mediated inflammatory diseases. Attempts to characterize TH 17 cells have demonstrated that they are highly dynamic, adjusting their function to environmental cues, which dictate their metabolic program. In this review, we highlight recent data demonstrating the impact of cellular metabolism on the TH 17/Treg balance and present factors that mediate TH 17-cell metabolism. Some examples of these include the differential impact of the mTOR signaling complexes on T-helper-cell differentiation, hypoxia inducible factor 1 alpha (HIF1α) promotion of glycolysis to favor TH 17-cell development, and ACC1-dependent de novo fatty acid synthesis favoring TH 17-cell development over Treg cells. Finally, we discuss the potential therapeutic options and the implications of modulating TH 17-cell metabolism for the treatment of TH 17-mediated diseases. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Metabolic Profiling of Impaired Cognitive Function in Patients Receiving Dialysis.

    Kurella Tamura, Manjula; Chertow, Glenn M; Depner, Thomas A; Nissenson, Allen R; Schiller, Brigitte; Mehta, Ravindra L; Liu, Sai; Sirich, Tammy L

    2016-12-01

    Retention of uremic metabolites is a proposed cause of cognitive impairment in patients with ESRD. We used metabolic profiling to identify and validate uremic metabolites associated with impairment in executive function in two cohorts of patients receiving maintenance dialysis. We performed metabolic profiling using liquid chromatography/mass spectrometry applied to predialysis plasma samples from a discovery cohort of 141 patients and an independent replication cohort of 180 patients participating in a trial of frequent hemodialysis. We assessed executive function with the Trail Making Test Part B and the Digit Symbol Substitution test. Impaired executive function was defined as a score ≥2 SDs below normative values. Four metabolites-4-hydroxyphenylacetate, phenylacetylglutamine, hippurate, and prolyl-hydroxyproline-were associated with impaired executive function at the false-detection rate significance threshold. After adjustment for demographic and clinical characteristics, the associations remained statistically significant: relative risk 1.16 (95% confidence interval [95% CI], 1.03 to 1.32), 1.39 (95% CI, 1.13 to 1.71), 1.24 (95% CI, 1.03 to 1.50), and 1.20 (95% CI, 1.05 to 1.38) for each SD increase in 4-hydroxyphenylacetate, phenylacetylglutamine, hippurate, and prolyl-hydroxyproline, respectively. The association between 4-hydroxyphenylacetate and impaired executive function was replicated in the second cohort (relative risk 1.12; 95% CI, 1.02 to 1.23), whereas the associations for phenylacetylglutamine, hippurate, and prolyl-hydroxyproline did not reach statistical significance in this cohort. In summary, four metabolites related to phenylalanine, benzoate, and glutamate metabolism may be markers of cognitive impairment in patients receiving maintenance dialysis. Copyright © 2016 by the American Society of Nephrology.

  9. Influence of revascularization on myocardial perfusion, metabolism and function

    Kropp, Joachim; Krois, Markus; Eichhorn, Bernd; Fehske, Wolfgang; Likungu, James; Kirchhoff, P.G.; Luederitz, Berndt; Biersack, Hans-Juergen; Knapp, F.F. Jr.

    1993-01-01

    Thirty-nine patients with coronary artery disease (CAD) were investigated with sequential SPECT-scintigraphy after administration of 200 MBq of 15-(p-[I-123]iodophenyl)pentadecanoic acid (IPPA) at peak submaximal exercise. Twenty patients underwent coronary angioplasty (PTCA) from which 14 had control coronary arteriography (CA) and left ventricular cineventriculography (LVCV). Nineteen patients underwent bypass graft surgery (ACB) and stress sonography. Semi-quantification of uptake (Up, related to perfusion) and turnover (Tr, linked to metabolism) was obtained by segmental comparison of oblique slices. About 90% of the reperfused myocardial segments in the PTCA-group and 76% in the ACB-group showed an improvement of uptake after therapy (RUp). Out of these, 50% and 66% exhibited increased turnover (RTr) after PTCA or ACB, respectively. The remaining segments had persistingly pathologic RTr indicating a dissociation of improvement of perfusion and metabolism after therapy. Pathologic RTr was highly correlated with regional wall motion abnormalities (RWMA) after therapy in both groups. In the ACB-group improvement in RTr was correlated with improved RWM at rest and stress in 86% and 92%, respectively, whereas no improvement in RTr was correlated with impared function in 100% and 52%, respectively. IPPA-studies show potential to provide information about changes of perfusion and metabolism after reperfusion and IPPA-turnover is a good predictor of the pattern of contractile function. (author)

  10. The measurement of the nigrostriatal dopaminergic function and glucose metabolism in patients with movement disorders

    Otsuka, Makoto; Ichiya, Yuichi; Kuwabara, Yasuo; Sasaki, Masayuki; Fukumura, Toshimitsu; Masuda, Kouji; Shima, Fumio; Kato, Motohiro (Kyushu Univ., Fukuoka (Japan). Faculty of Medicine)

    1992-12-01

    The nigrostriatal dopaminergic function and glucose metabolism were evaluated in 34 patients with various movement disorders by using positron emission tomography with [sup 18]F-Dopa and [sup 18]F-FDG respectively. The [sup 18]F-Dopa uptake in the striatum (the caudate head and the putamen) decreased in patients with Parkinson's disease but was relatively unaffected in the caudate. The cerebral glucose metabolism was normal in patients with Parkinson's disease. The [sup 18]F-Dopa uptake in the striatum also decreased in cases of atypical parkinsonism and in cases of progressive supranuclear palsy, but there was no difference in the uptake between the caudate and the putamen. The glucose metabolism decreased in the cerebral hemisphere including the striatum; this finding was also different from those of Parkinson's disease. A normal [sup 18]F-Dopa uptake in the striatum with a markedly decreased striatal glucose metabolism and a mildly decreased cortical glucose metabolism was observed in cases of Huntington's disease and Wilson's disease. The [sup 18]F-Dopa uptake in the striatum increased and the glucose metabolism was normal in cases of idiopathic dystonia. Various patterns of [sup 18]F-Dopa uptake and glucose metabolism were thus observed in the various movement disorders. These results suggest that the measurements of the [sup 18]F-Dopa uptake and the cerebral glucose metabolism would be useful for the evaluation of the striatal function in various movement disorders. (author).

  11. The human NAD metabolome: Functions, metabolism and compartmentalization

    Nikiforov, Andrey; Kulikova, Veronika; Ziegler, Mathias

    2015-01-01

    Abstract The metabolism of NAD has emerged as a key regulator of cellular and organismal homeostasis. Being a major component of both bioenergetic and signaling pathways, the molecule is ideally suited to regulate metabolism and major cellular events. In humans, NAD is synthesized from vitamin B3 precursors, most prominently from nicotinamide, which is the degradation product of all NAD-dependent signaling reactions. The scope of NAD-mediated regulatory processes is wide including enzyme regulation, control of gene expression and health span, DNA repair, cell cycle regulation and calcium signaling. In these processes, nicotinamide is cleaved from NAD+ and the remaining ADP-ribosyl moiety used to modify proteins (deacetylation by sirtuins or ADP-ribosylation) or to generate calcium-mobilizing agents such as cyclic ADP-ribose. This review will also emphasize the role of the intermediates in the NAD metabolome, their intra- and extra-cellular conversions and potential contributions to subcellular compartmentalization of NAD pools. PMID:25837229

  12. Use of density functional theory in drug metabolism studies

    Rydberg, Patrik; Jørgensen, Flemming Steen; Olsen, Lars

    2014-01-01

    INTRODUCTION: The cytochrome P450 enzymes (CYPs) metabolize many drug compounds. They catalyze a wide variety of reactions, and potentially, a large number of different metabolites can be generated. Density functional theory (DFT) has, over the past decade, been shown to be a powerful tool...... isoforms. This is probably due to the fact that the binding of the substrates is not the major determinant. When binding of the substrate plays a significant role, the well-known issue of determining the free energy of binding is the challenge. How approaches taking the protein environment into account...

  13. Brain Energy and Oxygen Metabolism: Emerging Role in Normal Function and Disease

    Michelle E. Watts

    2018-06-01

    Full Text Available Dynamic metabolic changes occurring in neurons are critically important in directing brain plasticity and cognitive function. In other tissue types, disruptions to metabolism and the resultant changes in cellular oxidative state, such as increased reactive oxygen species (ROS or induction of hypoxia, are associated with cellular stress. In the brain however, where drastic metabolic shifts occur to support physiological processes, subsequent changes to cellular oxidative state and induction of transcriptional sensors of oxidative stress likely play a significant role in regulating physiological neuronal function. Understanding the role of metabolism and metabolically-regulated genes in neuronal function will be critical in elucidating how cognitive functions are disrupted in pathological conditions where neuronal metabolism is affected. Here, we discuss known mechanisms regulating neuronal metabolism as well as the role of hypoxia and oxidative stress during normal and disrupted neuronal function. We also summarize recent studies implicating a role for metabolism in regulating neuronal plasticity as an emerging neuroscience paradigm.

  14. Physical, metabolic and developmental functions of the seed coat

    Radchuk, Volodymyr; Borisjuk, Ljudmilla

    2014-01-01

    The conventional understanding of the role of the seed coat is that it provides a protective layer for the developing zygote. Recent data show that the picture is more nuanced. The seed coat certainly represents a first line of defense against adverse external factors, but it also acts as channel for transmitting environmental cues to the interior of the seed. The latter function primes the seed to adjust its metabolism in response to changes in its external environment. The purpose of this review is to provide the reader with a comprehensive view of the structure and functionality of the seed coat, and to expose its hidden interaction with both the endosperm and embryo. Any breeding and/or biotechnology intervention seeking to increase seed size or modify seed features will have to consider the implications on this tripartite interaction. PMID:25346737

  15. New insights on glucosylated lipids: metabolism and functions.

    Ishibashi, Yohei; Kohyama-Koganeya, Ayako; Hirabayashi, Yoshio

    2013-09-01

    Ceramide, cholesterol, and phosphatidic acid are major basic structures for cell membrane lipids. These lipids are modified with glucose to generate glucosylceramide (GlcCer), cholesterylglucoside (ChlGlc), and phosphatidylglucoside (PtdGlc), respectively. Glucosylation dramatically changes the functional properties of lipids. For instance, ceramide acts as a strong tumor suppressor that causes apoptosis and cell cycle arrest, while GlcCer has an opposite effect, downregulating ceramide activities. All glucosylated lipids are enriched in lipid rafts or microdomains and play fundamental roles in a variety of cellular processes. In this review, we discuss the biological functions and metabolism of these three glucosylated lipids. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

  16. Effects of exercise program on physiological functions in postmenopausal women with metabolic syndrome.

    Heli, Valkeinen; Ihab, Hajjar; Kun, Hu; Brad, Manor; Jessica, Wisocky; Vera, Novak

    2013-12-01

    The purpose of this study was to examine effects of mixed interval aerobic and strength training (MAST) program on physiological functions in older women with metabolic syndrome. 12 subjects were randomly assigned to the exercise group (16-week MAST program) or the control group. Outcomes included oxygen uptake (VO 2max ), cerebral blood flow velocity (BFV) and cognitive functions. The exercise group demonstrated increased VO 2max and certain improvements in cognitive functions. No changes were observed in BFV for both groups. These results can be used as a preliminary data for planning larger studies.

  17. The international spinal cord injury endocrine and metabolic function basic data set.

    Bauman, W A; Biering-Sørensen, F; Krassioukov, A

    2011-10-01

    To develop the International Spinal Cord Injury (SCI) Endocrine and Metabolic Function Basic Data Set within the framework of the International SCI Data Sets that would facilitate consistent collection and reporting of basic endocrine and metabolic findings in the SCI population. International. The International SCI Endocrine and Metabolic Function Data Set was developed by a working group. The initial data set document was revised on the basis of suggestions from members of the Executive Committee of the International SCI Standards and Data Sets, the International Spinal Cord Society (ISCoS) Executive and Scientific Committees, American Spinal Injury Association (ASIA) Board, other interested organizations and societies, and individual reviewers. In addition, the data set was posted for 2 months on ISCoS and ASIA websites for comments. The final International SCI Endocrine and Metabolic Function Data Set contains questions on the endocrine and metabolic conditions diagnosed before and after spinal cord lesion. If available, information collected before injury is to be obtained only once, whereas information after injury may be collected at any time. These data include information on diabetes mellitus, lipid disorders, osteoporosis, thyroid disease, adrenal disease, gonadal disease and pituitary disease. The question of gonadal status includes stage of sexual development and that for females also includes menopausal status. Data will be collected for body mass index and for the fasting serum lipid profile. The complete instructions for data collection and the data sheet itself are freely available on the websites of ISCoS (http://www.iscos.org.uk) and ASIA (http://www.asia-spinalinjury.org).

  18. 2009 Plant Lipids: Structure, Metabolism & Function Gordon Research Conference - February 1- 6 ,2009

    Kent D. Chapman

    2009-02-06

    The Gordon Research Conference on 'Plant Lipids: Structure, Metabolism and Function' has been instituted to accelerate research productivity in the field of plant lipids. This conference will facilitate wide dissemination of research breakthroughs, support recruitment of young scientists to the field of plant lipid metabolism and encourage broad participation of the plant lipid community in guiding future directions for research in plant lipids. This conference will build upon the strengths of the successful, previous biannual meetings of the National Plant Lipid Cooperative (www.plantlipids.org) that began in 1993, but will reflect a broader scope of topics to include the biochemistry, cell biology, metabolic regulation, and signaling functions of plant acyl lipids. Most importantly, this conference also will serve as a physical focal point for the interaction of the plant lipid research community. Applications to attend this conference will be open to all researchers interested in plant lipids and will provide a venue for the presentation of the latest research results, networking opportunities for young scientists, and a forum for the development and exchange of useful lipid resources and new ideas. By bringing together senior- and junior-level scientists involved in plant lipid metabolism, a broad range of insights will be shared and the community of plant lipid researchers will function more as a network of vested partners. This is important for the vitality of the research community and for the perceived value that will encourage conference attendance into the future.

  19. Retinol Dehydrogenases Regulate Vitamin A Metabolism for Visual Function

    Bhubanananda Sahu

    2016-11-01

    Full Text Available The visual system produces visual chromophore, 11-cis-retinal from dietary vitamin A, all-trans-retinol making this vitamin essential for retinal health and function. These metabolic events are mediated by a sequential biochemical process called the visual cycle. Retinol dehydrogenases (RDHs are responsible for two reactions in the visual cycle performed in retinal pigmented epithelial (RPE cells, photoreceptor cells and Müller cells in the retina. RDHs in the RPE function as 11-cis-RDHs, which oxidize 11-cis-retinol to 11-cis-retinal in vivo. RDHs in rod photoreceptor cells in the retina work as all-trans-RDHs, which reduce all-trans-retinal to all-trans-retinol. Dysfunction of RDHs can cause inherited retinal diseases in humans. To facilitate further understanding of human diseases, mouse models of RDHs-related diseases have been carefully examined and have revealed the physiological contribution of specific RDHs to visual cycle function and overall retinal health. Herein we describe the function of RDHs in the RPE and the retina, particularly in rod photoreceptor cells, their regulatory properties for retinoid homeostasis and future therapeutic strategy for treatment of retinal diseases.

  20. Surfactant phosphatidylcholine metabolism and surfactant function in preterm, ventilated lambs

    Jobe, A.H.; Ikegami, M.; Seidner, S.R.; Pettenazzo, A.; Ruffini, L.

    1989-01-01

    Preterm lambs were delivered at 138 days gestational age and ventilated for periods up to 24 h in order to study surfactant metabolism and surfactant function. The surfactant-saturated phosphatidylcholine pool in the alveolar wash was 13 +/- 4 mumol/kg and did not change from 10 min to 24 h after birth. Trace amounts of labeled natural sheep surfactant were mixed with fetal lung fluid at birth. By 24 h, 80% of the label had become lung-tissue-associated, yet there was no loss of label from phosphatidylcholine in the lungs when calculated as the sum of the lung tissue plus alveolar wash. De novo synthesized phosphatidylcholine was labeled with choline given by intravascular injection at 1 h of age. Labeled phosphatidylcholine accumulated in the lung tissue linearly to 24 h, and the labeled phosphatidylcholine moved through lamellar body to alveolar pools. The turnover time for alveolar phosphatidylcholine was estimated to be about 13 h, indicating an active metabolic pool. A less surface-active surfactant fraction recovered as a supernatant after centrifugation of the alveolar washes at 40,000 x g increased from birth to 10 min of ventilation, but no subsequent changes in the distribution of surfactant phosphatidylcholine in surfactant fractions occurred. The results were consistent with recycling pathway(s) that maintained surface-active surfactant pools in preterm ventilated lambs

  1. Maternal blood metal levels and fetal markers of metabolic function

    Ashley-Martin, Jillian [Perinatal Epidemiology Research Unit, Dalhousie University, Halifax, Nova Scotia (Canada); Dodds, Linda, E-mail: l.dodds@dal.ca [Perinatal Epidemiology Research Unit, Dalhousie University, Halifax, Nova Scotia (Canada); Arbuckle, Tye E. [Health Canada, Ottawa (Canada); Ettinger, Adrienne S. [Yale University, New Haven, CT (United States); Shapiro, Gabriel D. [University of Montreal, Montreal, Quebec (Canada); CHU Sainte-Justine Research Centre, Montreal, Quebec (Canada); Fisher, Mandy [Health Canada, Ottawa (Canada); Taback, Shayne [University of Manitoba, Winnipeg, Manitoba (Canada); Bouchard, Maryse F. [University of Montreal, Montreal, Quebec (Canada); Monnier, Patricia [McGill University, Montreal, Quebec (Canada); Dallaire, Renee [Laval University, Quebec City, Quebec (Canada); Fraser, William D. [University of Montreal, Montreal, Quebec (Canada); CHU Sainte-Justine Research Centre, Montreal, Quebec (Canada)

    2015-01-15

    Exposure to metals commonly found in the environment has been hypothesized to be associated with measures of fetal growth but the epidemiological literature is limited. The Maternal–Infant Research on Environmental Chemicals (MIREC) study recruited 2001 women during the first trimester of pregnancy from 10 Canadian sites. Our objective was to assess the association between prenatal exposure to metals (lead, arsenic, cadmium, and mercury) and fetal metabolic function. Average maternal metal concentrations in 1st and 3rd trimester blood samples were used to represent prenatal metals exposure. Leptin and adiponectin were measured in 1363 cord blood samples and served as markers of fetal metabolic function. Polytomous logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between metals and both high (≥90%) and low (≤10%) fetal adiponectin and leptin levels. Leptin levels were significantly higher in female infants compared to males. A significant relationship between maternal blood cadmium and odds of high leptin was observed among males but not females in adjusted models. When adjusting for birth weight z-score, lead was associated with an increased odd of high leptin. No other significant associations were found at the top or bottom 10th percentile in either leptin or adiponectin models. This study supports the proposition that maternal levels of cadmium influence cord blood adipokine levels in a sex-dependent manner. Further investigation is required to confirm these findings and to determine how such findings at birth will translate into childhood anthropometric measures. - Highlights: • We determined relationships between maternal metal levels and cord blood adipokines. • Cord blood leptin levels were higher among female than male infants. • Maternal cadmium was associated with elevated leptin in male, not female infants. • No significant associations were observed between metals and

  2. Maternal blood metal levels and fetal markers of metabolic function

    Ashley-Martin, Jillian; Dodds, Linda; Arbuckle, Tye E.; Ettinger, Adrienne S.; Shapiro, Gabriel D.; Fisher, Mandy; Taback, Shayne; Bouchard, Maryse F.; Monnier, Patricia; Dallaire, Renee; Fraser, William D.

    2015-01-01

    Exposure to metals commonly found in the environment has been hypothesized to be associated with measures of fetal growth but the epidemiological literature is limited. The Maternal–Infant Research on Environmental Chemicals (MIREC) study recruited 2001 women during the first trimester of pregnancy from 10 Canadian sites. Our objective was to assess the association between prenatal exposure to metals (lead, arsenic, cadmium, and mercury) and fetal metabolic function. Average maternal metal concentrations in 1st and 3rd trimester blood samples were used to represent prenatal metals exposure. Leptin and adiponectin were measured in 1363 cord blood samples and served as markers of fetal metabolic function. Polytomous logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between metals and both high (≥90%) and low (≤10%) fetal adiponectin and leptin levels. Leptin levels were significantly higher in female infants compared to males. A significant relationship between maternal blood cadmium and odds of high leptin was observed among males but not females in adjusted models. When adjusting for birth weight z-score, lead was associated with an increased odd of high leptin. No other significant associations were found at the top or bottom 10th percentile in either leptin or adiponectin models. This study supports the proposition that maternal levels of cadmium influence cord blood adipokine levels in a sex-dependent manner. Further investigation is required to confirm these findings and to determine how such findings at birth will translate into childhood anthropometric measures. - Highlights: • We determined relationships between maternal metal levels and cord blood adipokines. • Cord blood leptin levels were higher among female than male infants. • Maternal cadmium was associated with elevated leptin in male, not female infants. • No significant associations were observed between metals and

  3. Glycogen metabolism protects against metabolic insult to preserve carotid body function during glucose deprivation.

    Holmes, Andrew P; Turner, Philip J; Carter, Paul; Leadbeater, Wendy; Ray, Clare J; Hauton, David; Buckler, Keith J; Kumar, Prem

    2014-10-15

    The view that the carotid body (CB) type I cells are direct physiological sensors of hypoglycaemia is challenged by the finding that the basal sensory neuronal outflow from the whole organ is unchanged in response to low glucose. The reason for this difference in viewpoint and how the whole CB maintains its metabolic integrity when exposed to low glucose is unknown. Here we show that, in the intact superfused rat CB, basal sensory neuronal activity was sustained during glucose deprivation for 29.1 ± 1.2 min, before irreversible failure following a brief period of excitation. Graded increases in the basal discharge induced by reducing the superfusate PO2 led to proportional decreases in the time to the pre-failure excitation during glucose deprivation which was dependent on a complete run-down in glycolysis and a fall in cellular energy status. A similar ability to withstand prolonged glucose deprivation was observed in isolated type I cells. Electron micrographs and immunofluorescence staining of rat CB sections revealed the presence of glycogen granules and the glycogen conversion enzymes glycogen synthase I and glycogen phosphorylase BB, dispersed throughout the type I cell cytoplasm. Furthermore, pharmacological attenuation of glycogenolysis and functional depletion of glycogen both significantly reduced the time to glycolytic run-down by ∼33 and 65%, respectively. These findings suggest that type I cell glycogen metabolism allows for the continuation of glycolysis and the maintenance of CB sensory neuronal output in periods of restricted glucose delivery and this may act as a key protective mechanism for the organ during hypoglycaemia. The ability, or otherwise, to preserve energetic status may thus account for variation in the reported capacity of the CB to sense physiological glucose concentrations and may even underlie its function during pathological states associated with augmented CB discharge. © 2014 The Authors. The Journal of Physiology © 2014

  4. Proposed physiologic functions of boron in plants pertinent to animal and human metabolism.

    Blevins, D G; Lukaszewski, K M

    1994-01-01

    Boron has been recognized since 1923 as an essential micronutrient element for higher plants. Over the years, many roles for boron in plants have been proposed, including functions in sugar transport, cell wall synthesis and lignification, cell wall structure, carbohydrate metabolism, RNA metabolism, respiration, indole acetic acid metabolism, phenol metabolism and membrane transport. However, the mechanism of boron involvement in each case remains unclear. Recent work has focused on two major plant-cell components: cell walls and membranes. In both, boron could play a structural role by bridging hydroxyl groups. In membranes, it could also be involved in ion transport and redox reactions by stimulating enzymes like nicotinamide adenine dinucleotide and reduced (NADH) oxidase. There is a very narrow window between the levels of boron required by and toxic to plants. The mechanisms of boron toxicity are also unknown. In nitrogen-fixing leguminous plants, foliarly applied boron causes up to a 1000% increase in the concentration of allantoic acid in leaves. In vitro studies show that boron inhibits the manganese-dependent allantoate amidohydrolase, and foliar application of manganese prior to application of boron eliminates allantoic acid accumulation in leaves. Interaction between borate and divalent cations like manganese may alter metabolic pathways, which could explain why higher concentrations of boron can be toxic to plants. PMID:7889877

  5. Functional Gene Diversity and Metabolic Potential of the Microbial Community in an Estuary-Shelf Environment

    Yu Wang

    2017-06-01

    Full Text Available Microbes play crucial roles in various biogeochemical processes in the ocean, including carbon (C, nitrogen (N, and phosphorus (P cycling. Functional gene diversity and the structure of the microbial community determines its metabolic potential and therefore its ecological function in the marine ecosystem. However, little is known about the functional gene composition and metabolic potential of bacterioplankton in estuary areas. The East China Sea (ECS is a dynamic marginal ecosystem in the western Pacific Ocean that is mainly affected by input from the Changjiang River and the Kuroshio Current. Here, using a high-throughput functional gene microarray (GeoChip, we analyzed the functional gene diversity, composition, structure, and metabolic potential of microbial assemblages in different ECS water masses. Four water masses determined by temperature and salinity relationship showed different patterns of functional gene diversity and composition. Generally, functional gene diversity [Shannon–Weaner’s H and reciprocal of Simpson’s 1/(1-D] in the surface water masses was higher than that in the bottom water masses. The different presence and proportion of functional genes involved in C, N, and P cycling among the bacteria of the different water masses showed different metabolic preferences of the microbial populations in the ECS. Genes involved in starch metabolism (amyA and nplT showed higher proportion in microbial communities of the surface water masses than of the bottom water masses. In contrast, a higher proportion of genes involved in chitin degradation was observed in microorganisms of the bottom water masses. Moreover, we found a higher proportion of nitrogen fixation (nifH, transformation of hydroxylamine to nitrite (hao and ammonification (gdh genes in the microbial communities of the bottom water masses compared with those of the surface water masses. The spatial variation of microbial functional genes was significantly correlated

  6. Effect of Dance Exercise on Cognitive Function in Elderly Patients with Metabolic Syndrome: A Pilot Study

    Kim, Se-Hong; Kim, Minjeong; Ahn, Yu-Bae; Lim, Hyun-Kook; Kang, Sung-Goo; Cho, Jung-hyoun; Park, Seo-Jin; Song, Sang-Wook

    2011-01-01

    Metabolic syndrome is associated with an increased risk of cognitive impairment. The purpose of this prospective pilot study was to examine the effects of dance exercise on cognitive function in elderly patients with metabolic syndrome. The participants included 38 elderly metabolic syndrome patients with normal cognitive function (26 exercise group and 12 control group). The exercise group performed dance exercise twice a week for 6 months. Cognitive function was assessed in all participants using the Korean version of the Consortium to Establish a Registry for Alzheimer’s disease (CERAD-K). Repeated-measures ANCOVA was used to assess the effect of dance exercise on cognitive function and cardiometabolic risk factors. Compared with the control group, the exercise group significantly improved in verbal fluency (p = 0.048), word list delayed recall (p = 0.038), word list recognition (p = 0.007), and total CERAD-K score (p = 0.037). However, no significance difference was found in body mass index, blood pressure, waist circumference, fasting plasma glucose, triglyceride, and HDL cholesterol between groups over the 6-month period. In the present study, six months of dance exercise improved cognitive function in older adults with metabolic syndrome. Thus, dance exercise may reduce the risk for cognitive disorders in elderly people with metabolic syndrome. Key points Metabolic syndrome (MS) is associated with an increased risk of cognitive impairment. Aerobic exercise improves cognitive function in elderly people and contributes to the prevention of degenerative neurological disease and brain damage. Dance sport is a form of aerobic exercise that has the additional benefits of stimulating the emotions, promoting social interaction, and exposing subjects to acoustic stimulation and music. In the present study, dance exercise for a 6-month period improved cognitive function in older adults with MS. In particular, positive effects were observed in verbal fluency, word

  7. Effect of dance exercise on cognitive function in elderly patients with metabolic syndrome: a pilot study.

    Kim, Se-Hong; Kim, Minjeong; Ahn, Yu-Bae; Lim, Hyun-Kook; Kang, Sung-Goo; Cho, Jung-Hyoun; Park, Seo-Jin; Song, Sang-Wook

    2011-01-01

    Metabolic syndrome is associated with an increased risk of cognitive impairment. The purpose of this prospective pilot study was to examine the effects of dance exercise on cognitive function in elderly patients with metabolic syndrome. The participants included 38 elderly metabolic syndrome patients with normal cognitive function (26 exercise group and 12 control group). The exercise group performed dance exercise twice a week for 6 months. Cognitive function was assessed in all participants using the Korean version of the Consortium to Establish a Registry for Alzheimer's disease (CERAD-K). Repeated-measures ANCOVA was used to assess the effect of dance exercise on cognitive function and cardiometabolic risk factors. Compared with the control group, the exercise group significantly improved in verbal fluency (p = 0.048), word list delayed recall (p = 0.038), word list recognition (p = 0.007), and total CERAD-K score (p = 0.037). However, no significance difference was found in body mass index, blood pressure, waist circumference, fasting plasma glucose, triglyceride, and HDL cholesterol between groups over the 6-month period. In the present study, six months of dance exercise improved cognitive function in older adults with metabolic syndrome. Thus, dance exercise may reduce the risk for cognitive disorders in elderly people with metabolic syndrome. Key pointsMetabolic syndrome (MS) is associated with an increased risk of cognitive impairment.Aerobic exercise improves cognitive function in elderly people and contributes to the prevention of degenerative neurological disease and brain damage. Dance sport is a form of aerobic exercise that has the additional benefits of stimulating the emotions, promoting social interaction, and exposing subjects to acoustic stimulation and music.In the present study, dance exercise for a 6-month period improved cognitive function in older adults with MS. In particular, positive effects were observed in verbal fluency, word list

  8. Intranasal administration of insulin to the brain impacts cognitive function and peripheral metabolism.

    Ott, V; Benedict, C; Schultes, B; Born, J; Hallschmid, M

    2012-03-01

    In recent years, the central nervous system (CNS) has emerged as a principal site of insulin action. This notion is supported by studies in animals relying on intracerebroventricular insulin infusion and by experiments in humans that make use of the intranasal pathway of insulin administration to the brain. Employing neurobehavioural and metabolic measurements as well as functional imaging techniques, these studies have provided insight into a broad range of central and peripheral effects of brain insulin. The present review focuses on CNS effects of insulin administered via the intranasal route on cognition, in particular memory function, and whole-body energy homeostasis including glucose metabolism. Furthermore, evidence is reviewed that suggests a pathophysiological role of impaired brain insulin signaling in obesity and type 2 diabetes, which are hallmarked by peripheral and possibly central nervous insulin resistance, as well as in conditions such as Alzheimer's disease where CNS insulin resistance might contribute to cognitive dysfunction. © 2011 Blackwell Publishing Ltd.

  9. Deciphering the mechanisms involved in Portulaca oleracea (C4) response to drought: metabolic changes including crassulacean acid-like metabolism induction and reversal upon re-watering.

    D'Andrea, Rodrigo Matías; Andreo, Carlos Santiago; Lara, María Valeria

    2014-11-01

    Portulaca oleracea is a C(4) plant; however, under drought it can change its carbon fixation metabolism into a crassulacean acid metabolism (CAM)-like one. While the C(3) -CAM shift is well known, the C(4) -CAM transition has only been described in Portulaca. Here, a CAM-like metabolism was induced in P. oleracea by drought and then reversed by re-watering. Physiological and biochemical approaches were undertaken to evaluate the drought and recovery responses. In CAM-like plants, chlorophyll fluorescence parameters were transitory affected and non-radiative energy dissipation mechanisms were induced. Induction of flavonoids, betalains and antioxidant machinery may be involved in photosynthetic machinery protection. Metabolic analysis highlights a clear metabolic shift, when a CAM-like metabolism is induced and then reversed. Increases in nitrogenous compounds like free amino acids and urea, and of pinitol could contribute to withstand drought. Reciprocal variations in arginase and urease in drought-stressed and in re-watered plants suggest urea synthesis is strictly regulated. Recovery of C(4) metabolism was accounted by CO(2) assimilation pattern and malate levels. Increases in glycerol and in polyamines would be of importance of re-watered plants. Collectively, in P. oleracea multiple strategies, from induction of several metabolites to the transitory development of a CAM-like metabolism, participate to enhance its adaptation to drought. © 2014 Scandinavian Plant Physiology Society.

  10. Metabolic syndrome and aerobic fitness in patients with first-episode schizophrenia, including a 1-year follow-up

    Nyboe, L.; Vestergaard, C. H.; Moeller, M. K.

    2015-01-01

    OBJECTIVE: To compare the prevalence of metabolic syndrome (MetS) and metabolic abnormalities in patients with first-episode schizophrenia (FES) with sex- and age-matched healthy controls; to investigate changes in MetS during 1year of treatment; and to investigate predictors of MetS. METHODS: Pa...

  11. Vascular endothelial growth factors: multitasking functionality in metabolism, health and disease.

    Smith, Gina A; Fearnley, Gareth W; Harrison, Michael A; Tomlinson, Darren C; Wheatcroft, Stephen B; Ponnambalam, Sreenivasan

    2015-07-01

    Vascular endothelial growth factors (VEGFs) bind to VEGF receptor tyrosine kinases (VEGFRs). The VEGF and VEGFR gene products regulate diverse regulatory pathways in mammalian development, health and disease. The interaction between a particular VEGF and its cognate VEGFR activates multiple signal transduction pathways which regulate different cellular responses including metabolism, gene expression, proliferation, migration, and survival. The family of VEGF isoforms regulate vascular physiology and promote tissue homeostasis. VEGF dysfunction is implicated in major chronic disease states including atherosclerosis, diabetes, and cancer. More recent studies implicate a strong link between response to VEGF and regulation of vascular metabolism. Understanding how this family of multitasking cytokines regulates cell and animal function has implications for treating many different diseases.

  12. Metabolic pattern analysis of early detection in Alzheimer's disease from other types of dementias and correlated with cognitive function

    Ju, R. H.; Lee, C. W.; Jung, Y. A.; Sohn, H. S.; Kim, S. H.; Seo, T. S

    2004-01-01

    PET/CT studies have demonstrated temporoparietal hypometabolism in probable and definite Alzheimer's disease (AD), a pattern that may help differentiate AD from other types of dementias. Seeking to distinguish Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD), we examined brain glucose metabolism of DLB and AD. Identification of individual differences in patterns of regional cerebral glucose metabolism (rCMRglc) interactions may be important for early detection of AD. We elucidate the relationship between reduced cognitive function and cerebral metabolism. Ten patients with the diagnosis of AD, 3 DLB patients underwent 18F-FDG PET CT. We applied statistical mapping procedure to evaluate the diagnostic power of rCMRglc patterns for differentiation and also correlated with Korean-mini mental status exam (K-MMSE) score include orientation time, place, registration, attention, calculation, recaIl, language and visuospatial function. Glucose metabolic pattern analysis confirmed AD and DLB patients showed significant metabolic reductions involving parietotemporal association, posterior cingulate, and frontal association cortex. DLB patients showed significant metabolic reductions in the occipital cortex, particularly in the primary visual cortex. Covariate analysis revealed that occipital metabolic changes in DLB were independent from those in the adjacent parietotemporal cortices. AnaIysis of clinically diagnosed probable AD patients showed a significantly higher frequency of primary visual metabolic reduction among patients who fulfilled clinical criteria for DLB. occipital hypometabolism is a potential discriminate marker to distinguish DLB versus AD

  13. Exploiting immune cell metabolic machinery for functional HIV cure and the prevention of inflammaging

    Palmer, Clovis S.; Palchaudhuri, Riya; Albargy, Hassan; Abdel-Mohsen, Mohamed; Crowe, Suzanne M.

    2018-01-01

    An emerging paradigm in immunology suggests that metabolic reprogramming and immune cell activation and functions are intricately linked. Viral infections, such as HIV infection, as well as cancer force immune cells to undergo major metabolic challenges. Cells must divert energy resources in order to mount an effective immune response. However, the fact that immune cells adopt specific metabolic programs to provide host defense against intracellular pathogens and how this metabolic shift impa...

  14. Direct fragmentation of quarkonia including Fermi motion using light-cone wave function

    Nobary, M.A. Gomshi [Razi University, Department of Physics, Faculty of Science, Kermanshah (Iran); A.E.O.I., Center for Theoretical Physics and Mathematics, Tehran (Iran); Javadi, B. [Razi University, Department of Physics, Faculty of Science, Kermanshah (Iran)

    2005-07-01

    We investigate the effect of Fermi motion on the direct fragmentation of the J/{psi} and {upsilon} states employing a light-cone wave function. Consistent with such a wave function we set up the kinematics of a heavy quark fragmenting into quarkonia such that the Fermi motion of the constituents splits into a longitudinal as well as a transverse direction and thus calculate the fragmentation functions for these states. In the framework of our investigation, we estimate that the fragmentation probabilities of J/{psi} and {upsilon} may increase at least up to 14 percent when including this degree of freedom. (orig.)

  15. Physical exercise restores microvascular function in obese rats with metabolic syndrome.

    Machado, Marcus Vinicius; Vieira, Aline Bomfim; Nascimento, Alessandro Rodrigues; Martins, Rômulo Lanza; Daleprane, Julio Beltrame; Lessa, Marcos Adriano; Tibiriçá, Eduardo

    2014-11-01

    Obesity and metabolic syndrome are related to systemic functional microvascular alterations, including a significant reduction in microvessel density. The aim of this study was to investigate the effects of exercise training on functional capillary density in the skeletal muscle and skin of obese rats with metabolic syndrome. We used male Wistar-Kyoto rats that had been fed a standard commercial diet (CON) or high-fat diet (HFD) for 32 weeks. Animals receiving the HFD were randomly divided into sedentary (HFD+SED) and training groups (HFD+TR) at the 20(th) week. After 12 weeks of aerobic treadmill training, the maximal oxygen uptake (VO2max); hemodynamic, biochemical, and anthropometric parameters; and functional capillary density were assessed. In addition, a maximal exercise test was performed. Exercise training increased the VO2max (69 ± 3 mL/kg per min) and exercise tolerance (30 ± 1 min) compared with the HFD+SED (41 ± 6 mL/kg per min, P Exercise training also increased the number of spontaneously perfused capillaries in the skeletal muscle (252 ± 9 vs. 207 ± 9 capillaries/mm(2)) of the training group compared with that in the sedentary animals (260 ± 15 capillaries/mm(2)). These results demonstrate that exercise training reverses capillary rarefaction in our experimental model of metabolic syndrome and obesity.

  16. Metabolism and Ovarian Function in PCOS Women: A Therapeutic Approach with Inositols

    Antonio Simone Laganà

    2016-01-01

    Full Text Available Polycystic ovary syndrome (PCOS is characterized by chronical anovulation and hyperandrogenism which may be present in a different degree of severity. Insulin-resistance and hyperinsulinemia are the main physiopathological basis of this syndrome and the failure of inositol-mediated signaling may concur to them. Myo (MI and D-chiro-inositol (DCI, the most studied inositol isoforms, are classified as insulin sensitizers. In form of glycans, DCI-phosphoglycan and MI-phosphoglycan control key enzymes were involved in glucose and lipid metabolism. In form of phosphoinositides, they play an important role as second messengers in several cellular biological functions. Considering the key role played by insulin-resistance and androgen excess in PCOS patients, the insulin-sensitizing effects of both MI and DCI were tested in order to ameliorate symptoms and signs of this syndrome, including the possibility to restore patients’ fertility. Accumulating evidence suggests that both isoforms of inositol are effective in improving ovarian function and metabolism in patients with PCOS, although MI showed the most marked effect on the metabolic profile, whereas DCI reduced hyperandrogenism better. The purpose of this review is to provide an update on inositol signaling and correlate data on biological functions of these multifaceted molecules, in view of a rational use for the therapy in women with PCOS.

  17. Age Drives Distortion of Brain Metabolic, Vascular and Cognitive Functions, and the Gut Microbiome

    Jared D. Hoffman

    2017-09-01

    Full Text Available Advancing age is the top risk factor for the development of neurodegenerative disorders, including Alzheimer’s disease (AD. However, the contribution of aging processes to AD etiology remains unclear. Emerging evidence shows that reduced brain metabolic and vascular functions occur decades before the onset of cognitive impairments, and these reductions are highly associated with low-grade, chronic inflammation developed in the brain over time. Interestingly, recent findings suggest that the gut microbiota may also play a critical role in modulating immune responses in the brain via the brain-gut axis. In this study, our goal was to identify associations between deleterious changes in brain metabolism, cerebral blood flow (CBF, gut microbiome and cognition in aging, and potential implications for AD development. We conducted our study with a group of young mice (5–6 months of age and compared those to old mice (18–20 months of age by utilizing metabolic profiling, neuroimaging, gut microbiome analysis, behavioral assessments and biochemical assays. We found that compared to young mice, old mice had significantly increased levels of numerous amino acids and fatty acids that are highly associated with inflammation and AD biomarkers. In the gut microbiome analyses, we found that old mice had increased Firmicutes/Bacteroidetes ratio and alpha diversity. We also found impaired blood-brain barrier (BBB function and reduced CBF as well as compromised learning and memory and increased anxiety, clinical symptoms often seen in AD patients, in old mice. Our study suggests that the aging process involves deleterious changes in brain metabolic, vascular and cognitive functions, and gut microbiome structure and diversity, all which may lead to inflammation and thus increase the risk for AD. Future studies conducting comprehensive and integrative characterization of brain aging, including crosstalk with peripheral systems and factors, will be necessary to

  18. Metabolic functions of Pseudomonas fluorescens strains from Populus deltoides depend on rhizosphere or endosphere isolation compartment

    Collin M Timm

    2015-10-01

    Full Text Available The bacterial microbiota of plants is diverse, with 1,000s of operational taxonomic units (OTUs associated with any individual plant. In this work we investigate the differences between 19 sequenced Pseudomonas fluorescens strains, isolated from Populus deltoides rhizosphere and endosphere and which represent a single OTU, using phenotypic analysis, comparative genomics, and metabolic models. While no traits were exclusive to either endosphere or rhizosphere P. fluorescens isolates, multiple pathways relevant for plant-bacterial interactions are enriched in endosphere isolate genomes. Further, growth phenotypes such as phosphate solubilization, protease activity, denitrification and root growth promotion are biased towards endosphere isolates. Endosphere isolates have significantly more metabolic pathways for plant signaling compounds and an increased metabolic range that includes utilization of energy rich nucleotides and sugars, consistent with endosphere colonization. Rhizosphere P. fluorescens have fewer pathways representative of plant-bacterial interactions but show metabolic bias towards chemical substrates often found in root exudates. This work reveals the diverse functions that may contribute to colonization of the endosphere by bacteria and are enriched among closely related isolates.

  19. β-cell function is associated with metabolic syndrome in Mexican subjects

    Baez-Duarte, Blanca G; Sánchez-Guillén, María Del Carmen; Pérez-Fuentes, Ricardo; Zamora-Ginez, Irma; Leon-Chavez, Bertha Alicia; Revilla-Monsalve, Cristina; Islas-Andrade, Sergio

    2010-01-01

    Aims The clinical diagnosis of metabolic syndrome does not find any parameters to evaluate the insulin sensitivity (IS) or β-cell function. The evaluation of these parameters would detect early risk of developing metabolic syndrome. The aim of this study is to determine the relationship between β-cell function and presence of metabolic syndrome in Mexican subjects. Material and methods This study is part of the Mexican Survey on the Prevention of Diabetes (MexDiab Study) with headquarters in ...

  20. Association between functional performance and executive cognitive functions in an elderly population including patients with low ankle–brachial index

    Ferreira, Naomi Vidal; Cunha, Paulo Jannuzzi; da Costa, Danielle Irigoyen; dos Santos, Fernando; Costa, Fernando Oliveira; Consolim-Colombo, Fernanda; Irigoyen, Maria Cláudia

    2015-01-01

    Introduction Peripheral arterial disease, as measured by the ankle–brachial index (ABI), is prevalent among the elderly, and is associated with functional performance, assessed by the 6-minute walk test (6MWT). Executive cognitive function (ECF) impairments are also prevalent in this population, but no existing study has investigated the association between ECF and functional performance in an elderly population including individuals with low ABI. Aim To investigate the association between functional performance, as measured by the 6MWT, and loss in ECF, in an elderly sample including individuals with low ABI. Method The ABI group was formed by 26 elderly individuals with low ABI (mean ABI: 0.63±0.19), and the control group was formed by 40 elderly individuals with normal ABI (mean ABI: 1.08±0.07). We analyzed functional performance using the 6MWT, global cognition using the Mini-Mental State Examination (MMSE), and ECF using the Digit Span for assessing attention span and working memory, the Stroop Color Word Test (SCWT) for assessing information processing speed and inhibitory control/impulsivity, and the Controlled Oral Word Association Test (COWAT) for assessing semantic verbal fluency and phonemic verbal fluency. We also used a factor analysis on all of the ECF tests (global ECF). Results Before adjustment, the ABI group performed worse on global cognition, attention span, working memory, inhibitory control/impulsivity, semantic verbal fluency, and phonemic verbal fluency. After adjustment, the ABI group performance remained worse for working memory and semantic verbal fluency. In a simple correlation analysis including all of the subjects, the 6MWT was associated with global cognition, attention span, working memory, information processing speed, inhibitory control/impulsivity, semantic verbal fluency, and global ECF. After adjustment, all the associations remained statistically significant. Conclusion This study found an independent association between

  1. A new wall function boundary condition including heat release effect for supersonic combustion flows

    Gao, Zhen-Xun; Jiang, Chong-Wen; Lee, Chun-Hian

    2016-01-01

    Highlights: • A new wall function including heat release effect is theoretically derived. • The new wall function is a unified form holding for flows with/without combustion. • The new wall function shows good results for a supersonic combustion case. - Abstract: A new wall function boundary condition considering combustion heat release effect (denoted as CWFBC) is proposed, for efficient predictions of skin friction and heat transfer in supersonic combustion flows. Based on a standard flow model including boundary-layer combustion, the Shvab–Zeldovich coupling parameters are introduced to derive a new velocity law-of-the-wall including the influence of combustion. For the temperature law-of-the-wall, it is proposed to use the enthalpy–velocity relation, instead of the Crocco–Busemann equation, to eliminate explicit influence of chemical reactions. The obtained velocity and temperature law-of-the-walls constitute the CWFBC, which is a unified form simultaneously holding for single-species, multi-species mixing and multi-species reactive flows. The subsequent numerical simulations using this CWFBC on an experimental case indicate that the CWFBC could accurately reflect the influences on the skin friction and heat transfer by the chemical reactions and heat release, and show large improvements compared to previous WFBC. Moreover, the CWFBC can give accurate skin friction and heat flux for a coarse mesh with y"+ up to 200 for the experimental case, except for slightly larger discrepancy of the wall heat flux around ignition position.

  2. Brain glucose sensing, glucokinase and neural control of metabolism and islet function.

    Ogunnowo-Bada, E O; Heeley, N; Brochard, L; Evans, M L

    2014-09-01

    It is increasingly apparent that the brain plays a central role in metabolic homeostasis, including the maintenance of blood glucose. This is achieved by various efferent pathways from the brain to periphery, which help control hepatic glucose flux and perhaps insulin-stimulated insulin secretion. Also, critically important for the brain given its dependence on a constant supply of glucose as a fuel--emergency counter-regulatory responses are triggered by the brain if blood glucose starts to fall. To exert these control functions, the brain needs to detect rapidly and accurately changes in blood glucose. In this review, we summarize some of the mechanisms postulated to play a role in this and examine the potential role of the low-affinity hexokinase, glucokinase, in the brain as a key part of some of this sensing. We also discuss how these processes may become altered in diabetes and related metabolic diseases. © 2014 John Wiley & Sons Ltd.

  3. Mitochondrial metabolism in hematopoietic stem cells requires functional FOXO3

    Rimmelé, Pauline; Liang, Raymond; Bigarella, Carolina L; Kocabas, Fatih; Xie, Jingjing; Serasinghe, Madhavika N; Chipuk, Jerry; Sadek, Hesham; Zhang, Cheng Cheng; Ghaffari, Saghi

    2015-01-01

    Hematopoietic stem cells (HSC) are primarily dormant but have the potential to become highly active on demand to reconstitute blood. This requires a swift metabolic switch from glycolysis to mitochondrial oxidative phosphorylation. Maintenance of low levels of reactive oxygen species (ROS), a by-product of mitochondrial metabolism, is also necessary for sustaining HSC dormancy. Little is known about mechanisms that integrate energy metabolism with hematopoietic stem cell homeostasis. Here, we identify the transcription factor FOXO3 as a new regulator of metabolic adaptation of HSC. ROS are elevated in Foxo3−/− HSC that are defective in their activity. We show that Foxo3−/− HSC are impaired in mitochondrial metabolism independent of ROS levels. These defects are associated with altered expression of mitochondrial/metabolic genes in Foxo3−/− hematopoietic stem and progenitor cells (HSPC). We further show that defects of Foxo3−/− HSC long-term repopulation activity are independent of ROS or mTOR signaling. Our results point to FOXO3 as a potential node that couples mitochondrial metabolism with HSC homeostasis. These findings have critical implications for mechanisms that promote malignant transformation and aging of blood stem and progenitor cells. PMID:26209246

  4. TS Fuzzy Model-Based Controller Design for a Class of Nonlinear Systems Including Nonsmooth Functions

    Vafamand, Navid; Asemani, Mohammad Hassan; Khayatiyan, Alireza

    2018-01-01

    This paper proposes a novel robust controller design for a class of nonlinear systems including hard nonlinearity functions. The proposed approach is based on Takagi-Sugeno (TS) fuzzy modeling, nonquadratic Lyapunov function, and nonparallel distributed compensation scheme. In this paper, a novel...... criterion, new robust controller design conditions in terms of linear matrix inequalities are derived. Three practical case studies, electric power steering system, a helicopter model and servo-mechanical system, are presented to demonstrate the importance of such class of nonlinear systems comprising...

  5. Beneficial effects of herbs, spices and medicinal plants on the metabolic syndrome, brain and cognitive function.

    Panickar, Kiran S

    2013-03-01

    Herbs and spices have been used since ancient times to not only improve the flavor of edible food but also to prevent and treat chronic health maladies. While the scientific evidence for the use of such common herbs and medicinal plants then had been scarce or lacking, the beneficial effects observed from such use were generally encouraging. It is, therefore, not surprising that the tradition of using such herbs, perhaps even after the advent of modern medicine, has continued. More recently, due to an increased interest in understanding the nutritional effects of herbs/spices more comprehensively, several studies have examined the cellular and molecular modes of action of the active chemical components in herbs and their biological properties. Beneficial actions of herbs/spices include anti-inflammatory, antioxidant, anti-hypertensive, gluco-regulatory, and anti-thrombotic effects. One major component of herbs and spices is the polyphenols. Some of the aforementioned properties are attributed to the polyphenols and they are associated with attenuating the metabolic syndrome. Detrimental changes associated with the metabolic syndrome over time affect brain and cognitive function. Metabolic syndrome and type-2 diabetes are also risk factors for Alzheimer's disease and stroke. In addition, the neuroprotective effects of herbs and spices have been demonstrated and, whether directly or indirectly, such beneficial effects may also contribute to an improvement in cognitive function. This review evaluates the current evidence available for herbs/spices in potentially improving the metabolic syndrome, as well as their neuroprotective effects on the brain, and cognitive function in animal and human studies.

  6. Novel metabolic and physiological functions of branched chain amino acids: a review

    Shihai Zhang; Xiangfang Zeng; Man Ren; Xiangbing Mao; Shiyan Qiao

    2017-01-01

    It is widely known that branched chain amino acids (BCAA) are not only elementary components for building muscle tissue but also participate in increasing protein synthesis in animals and humans.BCAA (isoleucine,leucine and valine) regulate many key signaling pathways,the most classic of which is the activation of the mTOR signaling pathway.This signaling pathway connects many diverse physiological and metabolic roles.Recent years have witnessed many striking developments in determining the novel functions of BCAA including:(1) Insufficient or excessive levels of BCAA in the diet enhances lipolysis.(2) BCAA,especially isoleucine,play a major role in enhancing glucose consumption and utilization by up-regulating intestinal and muscular glucose transporters.(3)Supplementation of leucine in the diet enhances meat quality in finishing pigs.(4) BCAA are beneficial for mammary health,milk quality and embryo growth.(5) BCAA enhance intestinal development,intestinal amino acid transportation and mucin production.(6) BCAA participate in up-regulating innate and adaptive immune responses.In addition,abnormally elevated BCAA levels in the blood (decreased BCAA catabolism) are a good biomarker for the early detection of obesity,diabetes and other metabolic diseases.This review will provide some insights into these novel metabolic and physiological functions of BCAA.

  7. Novel metabolic and physiological functions of branched chain amino acids: a review.

    Zhang, Shihai; Zeng, Xiangfang; Ren, Man; Mao, Xiangbing; Qiao, Shiyan

    2017-01-01

    It is widely known that branched chain amino acids (BCAA) are not only elementary components for building muscle tissue but also participate in increasing protein synthesis in animals and humans. BCAA (isoleucine, leucine and valine) regulate many key signaling pathways, the most classic of which is the activation of the mTOR signaling pathway. This signaling pathway connects many diverse physiological and metabolic roles. Recent years have witnessed many striking developments in determining the novel functions of BCAA including: (1) Insufficient or excessive levels of BCAA in the diet enhances lipolysis. (2) BCAA, especially isoleucine, play a major role in enhancing glucose consumption and utilization by up-regulating intestinal and muscular glucose transporters. (3) Supplementation of leucine in the diet enhances meat quality in finishing pigs. (4) BCAA are beneficial for mammary health, milk quality and embryo growth. (5) BCAA enhance intestinal development, intestinal amino acid transportation and mucin production. (6) BCAA participate in up-regulating innate and adaptive immune responses. In addition, abnormally elevated BCAA levels in the blood (decreased BCAA catabolism) are a good biomarker for the early detection of obesity, diabetes and other metabolic diseases. This review will provide some insights into these novel metabolic and physiological functions of BCAA.

  8. PORPHYRIN METABOLISM AND LIVER FUNCTION IN THE BANTU

    method for the detection of urinary coproporphyrin, Mentz5 calculated that ... defect in porphyrin metabolism which is commonly found in the Bantu could be ..... wood,61 traces of uroporphyrin may be excreted in normal urine. As much as 5 ...

  9. Metabolism

    ... Are More Common in People With Type 1 Diabetes Metabolic Syndrome Your Child's Weight Healthy Eating Endocrine System Blood Test: Basic Metabolic Panel (BMP) Activity: Endocrine System Growth Disorders Diabetes Center Thyroid Disorders Your Endocrine System Movie: Endocrine ...

  10. Stoichiometric Correlation Analysis: Principles of Metabolic Functionality from Metabolomics Data

    Kevin Schwahn

    2017-12-01

    Full Text Available Recent advances in metabolomics technologies have resulted in high-quality (time-resolved metabolic profiles with an increasing coverage of metabolic pathways. These data profiles represent read-outs from often non-linear dynamics of metabolic networks. Yet, metabolic profiles have largely been explored with regression-based approaches that only capture linear relationships, rendering it difficult to determine the extent to which the data reflect the underlying reaction rates and their couplings. Here we propose an approach termed Stoichiometric Correlation Analysis (SCA based on correlation between positive linear combinations of log-transformed metabolic profiles. The log-transformation is due to the evidence that metabolic networks can be modeled by mass action law and kinetics derived from it. Unlike the existing approaches which establish a relation between pairs of metabolites, SCA facilitates the discovery of higher-order dependence between more than two metabolites. By using a paradigmatic model of the tricarboxylic acid cycle we show that the higher-order dependence reflects the coupling of concentration of reactant complexes, capturing the subtle difference between the employed enzyme kinetics. Using time-resolved metabolic profiles from Arabidopsis thaliana and Escherichia coli, we show that SCA can be used to quantify the difference in coupling of reactant complexes, and hence, reaction rates, underlying the stringent response in these model organisms. By using SCA with data from natural variation of wild and domesticated wheat and tomato accession, we demonstrate that the domestication is accompanied by loss of such couplings, in these species. Therefore, application of SCA to metabolomics data from natural variation in wild and domesticated populations provides a mechanistic way to understanding domestication and its relation to metabolic networks.

  11. Representing uncertainty in objective functions: extension to include the influence of serial correlation

    Croke, B. F.

    2008-12-01

    The role of performance indicators is to give an accurate indication of the fit between a model and the system being modelled. As all measurements have an associated uncertainty (determining the significance that should be given to the measurement), performance indicators should take into account uncertainties in the observed quantities being modelled as well as in the model predictions (due to uncertainties in inputs, model parameters and model structure). In the presence of significant uncertainty in observed and modelled output of a system, failure to adequately account for variations in the uncertainties means that the objective function only gives a measure of how well the model fits the observations, not how well the model fits the system being modelled. Since in most cases, the interest lies in fitting the system response, it is vital that the objective function(s) be designed to account for these uncertainties. Most objective functions (e.g. those based on the sum of squared residuals) assume homoscedastic uncertainties. If model contribution to the variations in residuals can be ignored, then transformations (e.g. Box-Cox) can be used to remove (or at least significantly reduce) heteroscedasticity. An alternative which is more generally applicable is to explicitly represent the uncertainties in the observed and modelled values in the objective function. Previous work on this topic addressed the modifications to standard objective functions (Nash-Sutcliffe efficiency, RMSE, chi- squared, coefficient of determination) using the optimal weighted averaging approach. This paper extends this previous work; addressing the issue of serial correlation. A form for an objective function that includes serial correlation will be presented, and the impact on model fit discussed.

  12. Insulin in the nervous system and the mind: Functions in metabolism, memory, and mood.

    Lee, Seung-Hwan; Zabolotny, Janice M; Huang, Hu; Lee, Hyon; Kim, Young-Bum

    2016-08-01

    Insulin, a pleotrophic hormone, has diverse effects in the body. Recent work has highlighted the important role of insulin's action in the nervous system on glucose and energy homeostasis, memory, and mood. Here we review experimental and clinical work that has broadened the understanding of insulin's diverse functions in the central and peripheral nervous systems, including glucose and body weight homeostasis, memory and mood, with particular emphasis on intranasal insulin. Implications for the treatment of obesity, type 2 diabetes, dementia, and mood disorders are discussed in the context of brain insulin action. Intranasal insulin may have potential in the treatment of central nervous system-related metabolic disorders.

  13. Role of central nervous system in acute radiation syndrome functional metabolic encephalopathy

    Court, L.; Fatome, M.; Gueneau, J.; Rouif, G.; Pasquier, C.; Bassant, M.H.; Dufour, R.

    In adult rabbit, the effect on the brain of a whole-body or encephalic gamma irradiation is a function of the absorbed dose and begins after 25 rads. Three phases are described in the mechanism of radiation effect. In the initial phase, irradiation acts as a direct stimulus of cerebral structures. The second phase is a response towards aggression which includes: the effect of stimulation of various cerebral structures; their response and the induced feed-back mechanism; the release of metabolites inducing a functional metabolic encephalopathy in which occur: modification of blood pressure; modification of pulmonary ventilation; modification of acido-basic blood equilibrium. The third phase consists of functional recovery [fr

  14. Defining the breeding goal for a sheep breed including production and functional traits using market data.

    Theodoridis, A; Ragkos, A; Rose, G; Roustemis, D; Arsenos, G

    2017-11-16

    In this study, the economic values for production and functional traits of dairy sheep are estimated through the application of a profit function model using farm-level technical and economic data. The traits incorporated in the model were milk production, prolificacy, fertility, milking speed, longevity and mastitis occurrence. The economic values for these traits were derived as the approximate partial derivative of the specified profit function. A sensitivity analysis was also conducted in order to examine how potential changes in input and output prices would affect the breeding goal. The estimated economic values of the traits revealed their economic impact on the definition of the breeding goal for the specified production system. Milk production and fertility had the highest economic values (€40.30 and €20.28 per standard genetic deviation (SDa)), while, mastitis only had a low negative value of -0.57 €/SDa. Therefore, breeding for clinical mastitis will have a minor impact on farm profitability because it affects a small proportion of the flock and has low additive variance. The production traits, which include milk production, prolificacy and milking speed, contributed most to the breeding goal (70.0%), but functional traits still had a considerable share (30.0%). The results of this study highlight the importance of the knowledge of economic values of traits in the design of a breeding program. It is also suggested that the production and functional traits under consideration can be categorized as those which can be efficiently treated through genetic improvement (e.g. milk production and fertility) while others would be better dealt with through managerial interventions (e.g. mastitis occurrence). Also, sub-clinical mastitis that affects a higher proportion of flocks could have a higher contribution to breeding goals.

  15. Genetic modulation of energy metabolism in birds through mitochondrial function

    Tieleman, B. Irene; Versteegh, Maaike A.; Fries, Anthony; Helm, Barbara; Dingemanse, Niels J.; Gibbs, H. Lisle; Williams, Joseph B.

    2009-01-01

    Despite their central importance for the evolution of physiological variation, the genetic mechanisms that determine energy expenditure in animals have largely remained unstudied. We used quantitative genetics to confirm that both mass-specific and whole-organism basal metabolic rate (BMR) were

  16. Systematic inference of functional phosphorylation events in yeast metabolism

    Chen, Yu; Wang, Yonghong; Nielsen, Jens

    2017-01-01

    Motivation: Protein phosphorylation is a post-translational modification that affects proteins by changing their structure and conformation in a rapid and reversible way, and it is an important mechanism for metabolic regulation in cells. Phosphoproteomics enables high-throughput identification o...

  17. Simulation of Escherichia coli Dynamics in Biofilms and Submerged Colonies with an Individual-Based Model Including Metabolic Network Information.

    Tack, Ignace L M M; Nimmegeers, Philippe; Akkermans, Simen; Hashem, Ihab; Van Impe, Jan F M

    2017-01-01

    Clustered microbial communities are omnipresent in the food industry, e.g., as colonies of microbial pathogens in/on food media or as biofilms on food processing surfaces. These clustered communities are often characterized by metabolic differentiation among their constituting cells as a result of heterogeneous environmental conditions in the cellular surroundings. This paper focuses on the role of metabolic differentiation due to oxygen gradients in the development of Escherichia coli cell communities, whereby low local oxygen concentrations lead to cellular secretion of weak acid products. For this reason, a metabolic model has been developed for the facultative anaerobe E. coli covering the range of aerobic, microaerobic, and anaerobic environmental conditions. This metabolic model is expressed as a multiparametric programming problem, in which the influence of low extracellular pH values and the presence of undissociated acid cell products in the environment has been taken into account. Furthermore, the developed metabolic model is incorporated in MICRODIMS, an in-house developed individual-based modeling framework to simulate microbial colony and biofilm dynamics. Two case studies have been elaborated using the MICRODIMS simulator: (i) biofilm growth on a substratum surface and (ii) submerged colony growth in a semi-solid mixed food product. In the first case study, the acidification of the biofilm environment and the emergence of typical biofilm morphologies have been observed, such as the mushroom-shaped structure of mature biofilms and the formation of cellular chains at the exterior surface of the biofilm. The simulations show that these morphological phenomena are respectively dependent on the initial affinity of pioneer cells for the substratum surface and the cell detachment process at the outer surface of the biofilm. In the second case study, a no-growth zone emerges in the colony center due to a local decline of the environmental pH. As a result

  18. Simulation of Escherichia coli Dynamics in Biofilms and Submerged Colonies with an Individual-Based Model Including Metabolic Network Information

    Ignace L. M. M. Tack

    2017-12-01

    Full Text Available Clustered microbial communities are omnipresent in the food industry, e.g., as colonies of microbial pathogens in/on food media or as biofilms on food processing surfaces. These clustered communities are often characterized by metabolic differentiation among their constituting cells as a result of heterogeneous environmental conditions in the cellular surroundings. This paper focuses on the role of metabolic differentiation due to oxygen gradients in the development of Escherichia coli cell communities, whereby low local oxygen concentrations lead to cellular secretion of weak acid products. For this reason, a metabolic model has been developed for the facultative anaerobe E. coli covering the range of aerobic, microaerobic, and anaerobic environmental conditions. This metabolic model is expressed as a multiparametric programming problem, in which the influence of low extracellular pH values and the presence of undissociated acid cell products in the environment has been taken into account. Furthermore, the developed metabolic model is incorporated in MICRODIMS, an in-house developed individual-based modeling framework to simulate microbial colony and biofilm dynamics. Two case studies have been elaborated using the MICRODIMS simulator: (i biofilm growth on a substratum surface and (ii submerged colony growth in a semi-solid mixed food product. In the first case study, the acidification of the biofilm environment and the emergence of typical biofilm morphologies have been observed, such as the mushroom-shaped structure of mature biofilms and the formation of cellular chains at the exterior surface of the biofilm. The simulations show that these morphological phenomena are respectively dependent on the initial affinity of pioneer cells for the substratum surface and the cell detachment process at the outer surface of the biofilm. In the second case study, a no-growth zone emerges in the colony center due to a local decline of the environmental p

  19. Alteration of Fatty-Acid-Metabolizing Enzymes Affects Mitochondrial Form and Function in Hereditary Spastic Paraplegia

    Tesson, Christelle; Nawara, Magdalena; Salih, Mustafa A.M.; Rossignol, Rodrigue; Zaki, Maha S.; Al Balwi, Mohammed; Schule, Rebecca; Mignot, Cyril; Obre, Emilie; Bouhouche, Ahmed; Santorelli, Filippo M.; Durand, Christelle M.; Oteyza, Andrés Caballero; El-Hachimi, Khalid H.; Al Drees, Abdulmajeed; Bouslam, Naima; Lamari, Foudil; Elmalik, Salah A.; Kabiraj, Mohammad M.; Seidahmed, Mohammed Z.; Esteves, Typhaine; Gaussen, Marion; Monin, Marie-Lorraine; Gyapay, Gabor; Lechner, Doris; Gonzalez, Michael; Depienne, Christel; Mochel, Fanny; Lavie, Julie; Schols, Ludger; Lacombe, Didier; Yahyaoui, Mohamed; Al Abdulkareem, Ibrahim; Zuchner, Stephan; Yamashita, Atsushi; Benomar, Ali; Goizet, Cyril; Durr, Alexandra; Gleeson, Joseph G.; Darios, Frederic; Brice, Alexis; Stevanin, Giovanni

    2012-01-01

    Hereditary spastic paraplegia (HSP) is considered one of the most heterogeneous groups of neurological disorders, both clinically and genetically. The disease comprises pure and complex forms that clinically include slowly progressive lower-limb spasticity resulting from degeneration of the corticospinal tract. At least 48 loci accounting for these diseases have been mapped to date, and mutations have been identified in 22 genes, most of which play a role in intracellular trafficking. Here, we identified mutations in two functionally related genes (DDHD1 and CYP2U1) in individuals with autosomal-recessive forms of HSP by using either the classical positional cloning or a combination of whole-genome linkage mapping and next-generation sequencing. Interestingly, three subjects with CYP2U1 mutations presented with a thin corpus callosum, white-matter abnormalities, and/or calcification of the basal ganglia. These genes code for two enzymes involved in fatty-acid metabolism, and we have demonstrated in human cells that the HSP pathophysiology includes alteration of mitochondrial architecture and bioenergetics with increased oxidative stress. Our combined results focus attention on lipid metabolism as a critical HSP pathway with a deleterious impact on mitochondrial bioenergetic function. PMID:23176821

  20. The cross-tissue metabolic response of abalone (Haliotis midae) to functional hypoxia.

    Venter, Leonie; Loots, Du Toit; Mienie, Lodewyk J; Jansen van Rensburg, Peet J; Mason, Shayne; Vosloo, Andre; Lindeque, Jeremie Z

    2018-03-23

    Functional hypoxia is a stress condition caused by the abalone itself as a result of increased muscle activity, which generally necessitates the employment of anaerobic metabolism if the activity is sustained for prolonged periods. With that being said, abalone are highly reliant on anaerobic metabolism to provide partial compensation for energy production during oxygen-deprived episodes. However, current knowledge on the holistic metabolic response for energy metabolism during functional hypoxia, and the contribution of different metabolic pathways and various abalone tissues towards the overall accumulation of anaerobic end-products in abalone are scarce. Metabolomics analysis of adductor muscle, foot muscle, left gill, right gill, haemolymph and epipodial tissue samples indicated that South African abalone ( Haliotis midae) subjected to functional hypoxia utilises predominantly anaerobic metabolism, and depends on all of the main metabolite classes (proteins, carbohydrates and lipids) for energy supply. Functional hypoxia caused increased levels of anaerobic end-products: lactate, alanopine, tauropine, succinate and alanine. Also, elevation in arginine levels was detected, confirming that abalone use phosphoarginine to generate energy during functional hypoxia. Different tissues showed varied metabolic responses to hypoxia, with functional hypoxia showing excessive changes in the adductor muscle and gills. From this metabolomics investigation, it becomes evident that abalone are metabolically able to produce sufficient amounts of energy when functional hypoxia is experienced. Also, tissue interplay enables the adjustment of H. midae energy requirements as their metabolism shifts from aerobic to anaerobic respiration during functional hypoxia.This article has an associated First Person interview with the first author of the paper. © 2018. Published by The Company of Biologists Ltd.

  1. The cross-tissue metabolic response of abalone (Haliotis midae to functional hypoxia

    Leonie Venter

    2018-03-01

    Full Text Available Functional hypoxia is a stress condition caused by the abalone itself as a result of increased muscle activity, which generally necessitates the employment of anaerobic metabolism if the activity is sustained for prolonged periods. With that being said, abalone are highly reliant on anaerobic metabolism to provide partial compensation for energy production during oxygen-deprived episodes. However, current knowledge on the holistic metabolic response for energy metabolism during functional hypoxia, and the contribution of different metabolic pathways and various abalone tissues towards the overall accumulation of anaerobic end-products in abalone are scarce. Metabolomics analysis of adductor muscle, foot muscle, left gill, right gill, haemolymph and epipodial tissue samples indicated that South African abalone (Haliotis midae subjected to functional hypoxia utilises predominantly anaerobic metabolism, and depends on all of the main metabolite classes (proteins, carbohydrates and lipids for energy supply. Functional hypoxia caused increased levels of anaerobic end-products: lactate, alanopine, tauropine, succinate and alanine. Also, elevation in arginine levels was detected, confirming that abalone use phosphoarginine to generate energy during functional hypoxia. Different tissues showed varied metabolic responses to hypoxia, with functional hypoxia showing excessive changes in the adductor muscle and gills. From this metabolomics investigation, it becomes evident that abalone are metabolically able to produce sufficient amounts of energy when functional hypoxia is experienced. Also, tissue interplay enables the adjustment of H. midae energy requirements as their metabolism shifts from aerobic to anaerobic respiration during functional hypoxia. This article has an associated First Person interview with the first author of the paper.

  2. Knock-in/Knock-out (KIKO) vectors for rapid integration of large DNA sequences, including whole metabolic pathways, onto the Escherichia coli chromosome at well-characterised loci.

    Sabri, Suriana; Steen, Jennifer A; Bongers, Mareike; Nielsen, Lars K; Vickers, Claudia E

    2013-06-24

    Metabolic engineering projects often require integration of multiple genes in order to control the desired phenotype. However, this often requires iterative rounds of engineering because many current insertion approaches are limited by the size of the DNA that can be transferred onto the chromosome. Consequently, construction of highly engineered strains is very time-consuming. A lack of well-characterised insertion loci is also problematic. A series of knock-in/knock-out (KIKO) vectors was constructed for integration of large DNA sequences onto the E. coli chromosome at well-defined loci. The KIKO plasmids target three nonessential genes/operons as insertion sites: arsB (an arsenite transporter); lacZ (β-galactosidase); and rbsA-rbsR (a ribose metabolism operon). Two homologous 'arms' target each insertion locus; insertion is mediated by λ Red recombinase through these arms. Between the arms is a multiple cloning site for the introduction of exogenous sequences and an antibiotic resistance marker (either chloramphenicol or kanamycin) for selection of positive recombinants. The resistance marker can subsequently be removed by flippase-mediated recombination. The insertion cassette is flanked by hairpin loops to isolate it from the effects of external transcription at the integration locus. To characterize each target locus, a xylanase reporter gene (xynA) was integrated onto the chromosomes of E. coli strains W and K-12 using the KIKO vectors. Expression levels varied between loci, with the arsB locus consistently showing the highest level of expression. To demonstrate the simultaneous use of all three loci in one strain, xynA, green fluorescent protein (gfp) and a sucrose catabolic operon (cscAKB) were introduced into lacZ, arsB and rbsAR respectively, and shown to be functional. The KIKO plasmids are a useful tool for efficient integration of large DNA fragments (including multiple genes and pathways) into E. coli. Chromosomal insertion provides stable

  3. The international spinal cord injury endocrine and metabolic function basic data set

    Bauman, W A; Biering-Sørensen, Fin; Krassioukov, A

    2011-01-01

    To develop the International Spinal Cord Injury (SCI) Endocrine and Metabolic Function Basic Data Set within the framework of the International SCI Data Sets that would facilitate consistent collection and reporting of basic endocrine and metabolic findings in the SCI population....

  4. Etiopathophysiological assessment of cases with chronic daily headache: A functional magnetic resonance imaging included investigation

    Hashemi, Akram; Nami, Mohammad Torabi; Oghabian, Mohammad Ali; Ganjgahi, Habib; Vahabi, Zahra

    2012-01-01

    Background Chronic daily headache (CDH) has gained little attention in functional neuro-imaging. When no structural abnormality is found in CDH, defining functional correlates between activated brain regions during headache bouts may provide unique insights towards understanding the pathophysiology of this type of headache. Methods We recruited four CDH cases for comprehensive assessments, including history taking, physical examinations and neuropsychological evaluations (The Addenbrooke's Cognitive Evaluation, Beck's Anxiety and Depression Inventories, Pittsburg Sleep Quality Index and Epworth Sleepiness Scale). Visual analogue scale (VAS) was used to self-rate the intensity of headache. Patients then underwent electroencephalography (EEG), transcranial Doppler (TCD) and functional magnetic resonance imaging (fMRI) evaluations during maximal (VAS = 8-10/10) and off-headache (VAS = 0-3/10) conditions. Data were used to compare in both conditions. We also used BOLD (blood oxygen level dependent) -group level activation map fMRI to possibly locate headache-related activated brain regions. Results General and neurological examinations as well as conventional MRIs were unremarkable. Neuropsychological assessments showed moderate anxiety and depression in one patient and minimal in others. Unlike three patients, maximal and off-headache TCD evaluation in one revealed increased middle cerebral artery blood flow velocity, at the maximal pain area. Although with no seizure history, the same patient's EEG showed paroxysmal epileptic discharges during maximal headache intensity, respectively. Group level activation map fMRI showed activated classical pain matrix regions upon headache bouts (periaqueductal grey, substantia nigra and raphe nucleus), and markedly bilateral occipital lobes activation. Conclusion The EEG changes were of note. Furthermore, the increased BOLD signals in areas outside the classical pain matrix (i.e. occipital lobes) during maximal headaches may

  5. [Functional results of cryosurgical procedures in rhegmatogenous retinal detachment including macula region - our experience].

    Chrapek, O; Sín, M; Jirková, B; Jarkovský, J; Rehák, J

    2013-10-01

    Aim of this study is to evaluate retrospectively functional results of cryosurgical treatment of uncomplicated, idiopathic rhegmatogenous retinal detachment including macula region in phakic patients operated on at the Department of Ophthalmology, Faculty Hospital, Palacký University, Olomouc, Czech Republic, E.U., during the period 2002 -2013, and to evaluate the significance of the macula detachment duration for the final visual acuity. In the study group were included 56 eyes of 56 patients operated in the years 2003 - 2012 at the Department of Ophthalmology, Faculty Hospital, Palacký University, Olomouc. All patients were phakic and in all of them, the retinal detachment including the macula region was diagnosed. The mean follow-up period of the patients was 8,75 months. The initial and final visual acuity testing were performed. Comparing the initial and final visual acuity we rated the level of the visual acuity change. The result was stated as improved, if the visual acuity improved by 1 or more lines on the ETDRS chart. The result was rated as stabilized, if the visual acuity remained the same or it changed by 1 line of the ETDRS chart only. The result was evaluated as worsened, if the visual acuity decreased by 1 or more lines of the ETDRS chart. In the followed-up group, the authors compared visual acuity levels in patients with the macula detachment duration 10 days and 11 days. For the statistical evaluation of achieved results, the Mann - Whitney U test was used. The visual acuity improved in 49 (87 %), did not changed in 5 (9 %) and worsened in 2 (4 %) patients. The patients with macula detachment duration 10 days achieved statistically significant better visual acuity than patients with macula detachment duration 11 days. Patients with macula detachment duration 10 days have better prognosis for functional result than patients with macula detachment duration 11 days.

  6. Metabolic enzymes: key modulators of functionality in cancer stem-like cells.

    Dong, Bo-Wen; Qin, Guang-Ming; Luo, Yan; Mao, Jian-Shan

    2017-02-21

    Cancer Stem-like Cells (CSCs) are a subpopulation of cancer cells with self-renewal capacity and are important for the initiation, progression and recurrence of cancer diseases. The metabolic profile of CSCs is consistent with their stem-like properties. Studies have indicated that enzymes, the main regulators of cellular metabolism, dictate functionalities of CSCs in both catalysis-dependent and catalysis-independent manners. This paper reviews diverse studies of metabolic enzymes, and describes the effects of these enzymes on metabolic adaptation, gene transcription and signal transduction, in CSCs.

  7. Effects of magnesium supplements on blood pressure, endothelial function and metabolic parameters in healthy young men with a family history of metabolic syndrome.

    Cosaro, E; Bonafini, S; Montagnana, M; Danese, E; Trettene, M S; Minuz, P; Delva, P; Fava, C

    2014-11-01

    Magnesium plays an important role in the modulation of vascular tone and endothelial function and can regulate glucose and lipid metabolism. Patients with hypertension, metabolic syndrome (MetS) and diabetes mellitus (T2DM) have low body magnesium content; indeed, magnesium supplementation has been shown to have a positive effect on blood pressure (BP) and gluco-metabolic parameters. The aim of our study was to evaluate the effect of magnesium supplements on hemodynamic and metabolic parameters in healthy men with a positive family history of MetS or T2DM. In a randomized, double-blind, placebo-controlled 8-week crossover trial with a 4 week wash-out period, oral supplements of 8.1 mmol of magnesium-pidolate or placebo were administered twice a day to 14 healthy normomagnesemic participants, aged 23-33 years. The primary endpoint was office BP, measured with a semiautomatic oscillometric device. Secondary endpoints included characteristics of the MetS, namely endothelial function, arterial stiffness and inflammation. Plasma and urinary magnesium were measured in all participants while free intracellular magnesium was measured only in a subsample. There was no significant difference in either systolic and diastolic BP in participants post-magnesium supplementation and post-placebo treatment when compared to baseline BP measurements. Further, the metabolic, inflammatory and hemodynamic parameters did not vary significantly during the study. Our study showed no beneficial effect of magnesium supplements on BP, vascular function and glycolipid profile in young men with a family history of MetS/T2DM (trial registration at clinicaltrial.gov ID: NCT01181830; 12th of Aug 2010). Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Metabolism

    ... lin), which signals cells to increase their anabolic activities. Metabolism is a complicated chemical process, so it's not ... how those enzymes or hormones work. When the metabolism of body chemicals is ... Hyperthyroidism (pronounced: hi-per-THIGH-roy-dih-zum). Hyperthyroidism ...

  9. Creatine, energetic function, metabolism and supplementation effects on sports

    Emerson Gimenes Bernardo da Silva

    2008-06-01

    Full Text Available The purpose of this work is to review the literature regarding creatine ingestion by athletes and physical activity enthusiasts, discussing its necessity and, if possible, predicting some consequences. In order to achieve this purpose it was necessary to study the relationship between the muscles energetic system and their regulation. It was also proved necessary to investigate the creatine cycle, its endogenous origin, its metabolizing and conversion into creatine-phosphate. A bibliography was used to collect information about the subject. The research lead to the following conclusions: diet supplementation with creatine leads to increased phosphocreatine levels in human muscles. However, new in vivo experiments are most desirable, because it is already known that creatine interferes with the regulation of some metabolic pathways.

  10. Biological functions of histidine-dipeptides and metabolic syndrome

    Song, Byeng Chun; Joo, Nam-Seok; Aldini, Giancarlo; Yeum, Kyung-Jin

    2014-01-01

    The rapid increase in the prevalence of metabolic syndrome, which is associated with a state of elevated systemic oxidative stress and inflammation, is expected to cause future increases in the prevalence of diabetes and cardiovascular diseases. Oxidation of polyunsaturated fatty acids and sugars produces reactive carbonyl species, which, due to their electrophilic nature, react with the nucleophilic sites of certain amino acids. This leads to formation of protein adducts such as advanced gly...

  11. Succession of the functional microbial communities and the metabolic functions in maize straw composting process.

    Wei, Huawei; Wang, Liuhong; Hassan, Muhammad; Xie, Bing

    2018-05-01

    Illumina MiSeq sequencing and phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) were applied to study the dynamic changes and effects of microbial community structures as well as the metabolic function of bacterial community in maize straw composting process. Results showed that humic acid contents in loosely combined humus (HA1) and stably combined humus (HA2) increased after composting and Staphylococcus, Cellulosimicrobium and Ochrobactrum possibly participated in the transformation of the process. The bacterial communities differed in different stages of the composting. Firmicutes, Proteobacteria, Bacteroidetes and Actinobacteria were reported the dominant phyla throughout the process and the relative abundance of the dominant phyla varied significantly (p composting. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. Communication: importance sampling including path correlation in semiclassical initial value representation calculations for time correlation functions.

    Pan, Feng; Tao, Guohua

    2013-03-07

    Full semiclassical (SC) initial value representation (IVR) for time correlation functions involves a double phase space average over a set of two phase points, each of which evolves along a classical path. Conventionally, the two initial phase points are sampled independently for all degrees of freedom (DOF) in the Monte Carlo procedure. Here, we present an efficient importance sampling scheme by including the path correlation between the two initial phase points for the bath DOF, which greatly improves the performance of the SC-IVR calculations for large molecular systems. Satisfactory convergence in the study of quantum coherence in vibrational relaxation has been achieved for a benchmark system-bath model with up to 21 DOF.

  13. How Energy Metabolism Supports Cerebral Function: Insights from 13C Magnetic Resonance Studies In vivo

    Sarah Sonnay

    2017-05-01

    Full Text Available Cerebral function is associated with exceptionally high metabolic activity, and requires continuous supply of oxygen and nutrients from the blood stream. Since the mid-twentieth century the idea that brain energy metabolism is coupled to neuronal activity has emerged, and a number of studies supported this hypothesis. Moreover, brain energy metabolism was demonstrated to be compartmentalized in neurons and astrocytes, and astrocytic glycolysis was proposed to serve the energetic demands of glutamatergic activity. Shedding light on the role of astrocytes in brain metabolism, the earlier picture of astrocytes being restricted to a scaffold-associated function in the brain is now out of date. With the development and optimization of non-invasive techniques, such as nuclear magnetic resonance spectroscopy (MRS, several groups have worked on assessing cerebral metabolism in vivo. In this context, 1H MRS has allowed the measurements of energy metabolism-related compounds, whose concentrations can vary under different brain activation states. 1H-[13C] MRS, i.e., indirect detection of signals from 13C-coupled 1H, together with infusion of 13C-enriched glucose has provided insights into the coupling between neurotransmission and glucose oxidation. Although these techniques tackle the coupling between neuronal activity and metabolism, they lack chemical specificity and fail in providing information on neuronal and glial metabolic pathways underlying those processes. Currently, the improvement of detection modalities (i.e., direct detection of 13C isotopomers, the progress in building adequate mathematical models along with the increase in magnetic field strength now available render possible detailed compartmentalized metabolic flux characterization. In particular, direct 13C MRS offers more detailed dataset acquisitions and provides information on metabolic interactions between neurons and astrocytes, and their role in supporting neurotransmission. Here

  14. Rhinal hypometabolism on FDG PET in healthy APO-E4 carriers: impact on memory function and metabolic networks

    Didic, Mira; Felician, Olivier; Gour, Natalina; Ceccaldi, Mathieu; Bernard, Rafaelle; Pecheux, Christophe; Mundler, Olivier; Guedj, Eric

    2015-01-01

    The ε4 allele of the apolipoprotein E (APO-E4) gene, a genetic risk factor for Alzheimer's disease (AD), also modulates brain metabolism and function in healthy subjects. The aim of the present study was to explore cerebral metabolism using FDG PET in healthy APO-E4 carriers by comparing cognitively normal APO-E4 carriers to noncarriers and to assess if patterns of metabolism are correlated with performance on cognitive tasks. Moreover, metabolic connectivity patterns were established in order to assess if the organization of neural networks is influenced by genetic factors. Whole-brain PET statistical analysis was performed at voxel-level using SPM8 with a threshold of p < 0.005, corrected for volume, with age, gender and level of education as nuisance variables. Significant hypometabolism between APO-E4 carriers (n = 11) and noncarriers (n = 30) was first determined. Mean metabolic values with clinical/neuropsychological data were extracted at the individual level, and correlations were searched using Spearman's rank test in the whole group. To evaluate metabolic connectivity from metabolic cluster(s) previously identified in the intergroup comparison, voxel-wise interregional correlation analysis (IRCA) was performed between groups of subjects. APO-E4 carriers had reduced metabolism within the left anterior medial temporal lobe (MTL), where neuropathological changes first appear in AD, including the entorhinal and perirhinal cortices. A correlation between metabolism in this area and performance on the DMS48 (delayed matching to sample-48 items) was found, in line with converging evidence involving the perirhinal cortex in object-based memory. Finally, a voxel-wise IRCA revealed stronger metabolic connectivity of the MTL cluster with neocortical frontoparietal regions in carriers than in noncarriers, suggesting compensatory metabolic networks. Exploring cerebral metabolism using FDG PET can contribute to a better understanding of the influence of

  15. Rhinal hypometabolism on FDG PET in healthy APO-E4 carriers: impact on memory function and metabolic networks

    Didic, Mira; Felician, Olivier; Gour, Natalina; Ceccaldi, Mathieu [Pole de Neurosciences Cliniques, Centre Hospitalo-Universitaire de la Timone, AP-HM, Service de Neurologie and Neuropsychologie, Marseille (France); Aix Marseille Universite, Inserm, INS UMRS 1106, Marseille (France); Bernard, Rafaelle; Pecheux, Christophe [Centre Hospitalo-Universitaire de la Timone, AP-HM, et INSERM UMRS 910: ' ' Genetique Medicale et Genomique fonctionnelle' ' , Departement de Genetique Medicale, Marseille (France); Mundler, Olivier; Guedj, Eric [Centre Hospitalo-Universitaire de la Timone, AP-HM, Service Central de Biophysique et Medecine Nucleaire, Marseille (France); Aix Marseille Universite, CERIMED, CNRS UMR7289, INT, Marseille (France); Aix Marseille Universite, CNRS UMR7289, INT, Marseille (France)

    2015-09-15

    The ε4 allele of the apolipoprotein E (APO-E4) gene, a genetic risk factor for Alzheimer's disease (AD), also modulates brain metabolism and function in healthy subjects. The aim of the present study was to explore cerebral metabolism using FDG PET in healthy APO-E4 carriers by comparing cognitively normal APO-E4 carriers to noncarriers and to assess if patterns of metabolism are correlated with performance on cognitive tasks. Moreover, metabolic connectivity patterns were established in order to assess if the organization of neural networks is influenced by genetic factors. Whole-brain PET statistical analysis was performed at voxel-level using SPM8 with a threshold of p < 0.005, corrected for volume, with age, gender and level of education as nuisance variables. Significant hypometabolism between APO-E4 carriers (n = 11) and noncarriers (n = 30) was first determined. Mean metabolic values with clinical/neuropsychological data were extracted at the individual level, and correlations were searched using Spearman's rank test in the whole group. To evaluate metabolic connectivity from metabolic cluster(s) previously identified in the intergroup comparison, voxel-wise interregional correlation analysis (IRCA) was performed between groups of subjects. APO-E4 carriers had reduced metabolism within the left anterior medial temporal lobe (MTL), where neuropathological changes first appear in AD, including the entorhinal and perirhinal cortices. A correlation between metabolism in this area and performance on the DMS48 (delayed matching to sample-48 items) was found, in line with converging evidence involving the perirhinal cortex in object-based memory. Finally, a voxel-wise IRCA revealed stronger metabolic connectivity of the MTL cluster with neocortical frontoparietal regions in carriers than in noncarriers, suggesting compensatory metabolic networks. Exploring cerebral metabolism using FDG PET can contribute to a better understanding of the influence of

  16. Recent insights into the implications of metabolism in plasmacytoid dendritic cell innate functions: Potential ways to control these functions [version 2; referees: 1 approved, 2 approved with reservations

    Philippe Saas

    2017-06-01

    Full Text Available There are more and more data concerning the role of cellular metabolism in innate immune cells, such as macrophages or conventional dendritic cells. However, few data are available currently concerning plasmacytoid dendritic cells (PDC, another type of innate immune cells. These cells are the main type I interferon (IFN producing cells, but they also secrete other pro-inflammatory cytokines (e.g., tumor necrosis factor or interleukin [IL]-6 or immunomodulatory factors (e.g., IL-10 or transforming growth factor-β. Through these functions, PDC participate in antimicrobial responses or maintenance of immune tolerance, and have been implicated in the pathophysiology of several autoimmune diseases, as well as in tumor immune escape mechanisms. Recent data support the idea that the glycolytic pathway (or glycolysis, as well as lipid metabolism (including both cholesterol and fatty acid metabolism may impact some innate immune functions of PDC or may be involved in these functions after Toll-like receptor (TLR 7/9 triggering. The kinetics of glycolysis after TLR7/9 triggering may differ between human and murine PDC. In mouse PDC, metabolism changes promoted by TLR7/9 activation may depend on an autocrine/paracrine loop, implicating type I IFN and its receptor IFNAR. This could explain a delayed glycolysis in mouse PDC. Moreover, PDC functions can be modulated by the metabolism of cholesterol and fatty acids. This may occur via the production of lipid ligands that activate nuclear receptors (e.g., liver X receptor [LXR] in PDC or through limiting intracellular cholesterol pool size (by statin or LXR agonist treatment in these cells. Finally, lipid-activated nuclear receptors (i.e., LXR or peroxisome proliferator activated receptor may also directly interact with pro-inflammatory transcription factors, such as NF-κB. Here, we discuss how glycolysis and lipid metabolism may modulate PDC functions and how this may be harnessed in pathological situations

  17. Microbial metaproteomics for characterizing the range of metabolic functions and activities of human gut microbiota.

    Xiong, Weili; Abraham, Paul E; Li, Zhou; Pan, Chongle; Hettich, Robert L

    2015-10-01

    The human gastrointestinal tract is a complex, dynamic ecosystem that consists of a carefully tuned balance of human host and microbiota membership. The microbiome is not merely a collection of opportunistic parasites, but rather provides important functions to the host that are absolutely critical to many aspects of health, including nutrient transformation and absorption, drug metabolism, pathogen defense, and immune system development. Microbial metaproteomics provides the ability to characterize the human gut microbiota functions and metabolic activities at a remarkably deep level, revealing information about microbiome development and stability as well as their interactions with their human host. Generally, microbial and human proteins can be extracted and then measured by high performance MS-based proteomics technology. Here, we review the field of human gut microbiome metaproteomics, with a focus on the experimental and informatics considerations involved in characterizing systems ranging from low-complexity model gut microbiota in gnotobiotic mice, to the emerging gut microbiome in the GI tract of newborn human infants, and finally to an established gut microbiota in human adults. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Overexpression of SIRT1 in mouse forebrain impairs lipid/glucose metabolism and motor function.

    Dongmei Wu

    Full Text Available SIRT1 plays crucial roles in glucose and lipid metabolism, and has various functions in different tissues including brain. The brain-specific SIRT1 knockout mice display defects in somatotropic signaling, memory and synaptic plasticity. And the female mice without SIRT1 in POMC neuron are more sensitive to diet-induced obesity. Here we created transgenic mice overexpressing SIRT1 in striatum and hippocampus under the control of CaMKIIα promoter. These mice, especially females, exhibited increased fat accumulation accompanied by significant upregulation of adipogenic genes in white adipose tissue. Glucose tolerance of the mice was also impaired with decreased Glut4 mRNA levels in muscle. Moreover, the SIRT1 overexpressing mice showed decreased energy expenditure, and concomitantly mitochondria-related genes were decreased in muscle. In addition, these mice showed unusual spontaneous physical activity pattern, decreased activity in open field and rotarod performance. Further studies demonstrated that SIRT1 deacetylated IRS-2, and upregulated phosphorylation level of IRS-2 and ERK1/2 in striatum. Meanwhile, the neurotransmitter signaling in striatum and the expression of endocrine hormones in hypothalamus and serum T3, T4 levels were altered. Taken together, our findings demonstrate that SIRT1 in forebrain regulates lipid/glucose metabolism and motor function.

  19. Functional analysis of the global repressor Tup1 for maltose metabolism in Saccharomyces cerevisiae: different roles of the functional domains.

    Lin, Xue; Yu, Ai-Qun; Zhang, Cui-Ying; Pi, Li; Bai, Xiao-Wen; Xiao, Dong-Guang

    2017-11-09

    Tup1 is a general transcriptional repressor of diverse gene families coordinately controlled by glucose repression, mating type, and other mechanisms in Saccharomyces cerevisiae. Several functional domains of Tup1 have been identified, each of which has differing effects on transcriptional repression. In this study, we aim to investigate the role of Tup1 and its domains in maltose metabolism of industrial baker's yeast. To this end, a battery of in-frame truncations in the TUP1 gene coding region were performed in the industrial baker's yeasts with different genetic background, and the maltose metabolism, leavening ability, MAL gene expression levels, and growth characteristics were investigated. The results suggest that the TUP1 gene is essential to maltose metabolism in industrial baker's yeast. Importantly, different domains of Tup1 play different roles in glucose repression and maltose metabolism of industrial baker's yeast cells. The Ssn6 interaction, N-terminal repression and C-terminal repression domains might play roles in the regulation of MAL transcription by Tup1 for maltose metabolism of baker's yeast. The WD region lacking the first repeat could influence the regulation of maltose metabolism directly, rather than indirectly through glucose repression. These findings lay a foundation for the optimization of industrial baker's yeast strains for accelerated maltose metabolism and facilitate future research on glucose repression in other sugar metabolism.

  20. Gancao-Gansui combination impacts gut microbiota diversity and related metabolic functions.

    Yu, Jingao; Guo, Jianming; Tao, Weiwei; Liu, Pei; Shang, Erxin; Zhu, Zhenhua; Fan, Xiuhe; Shen, Juan; Hua, Yongqing; Zhu, Kevin Yue; Tang, Yuping; Duan, Jin-Ao

    2018-03-25

    The theory of "eighteen incompatible medicaments" (EIM) in traditional Chinese medicine (TCM) is the most representative case of herbal-herbal interactions. Gancao and Gansui are one of the incompatible herbal pairs in EIM. Gancao, also known as "licorice", is the most frequently used Chinese herb or food additive. Gansui, the root of Euphorbia kansui T.P. Wang, is another famous Chinese herb usually used to treat edema, ascites and asthma but could induce gastrointestinal (GI) tract irritation. Although Gancao and Gansui are incompatible herbal pairs, they are still used in combination in the famous "Gansui-Banxia" decoction. This study was conducted to investigate if Gancao-Gansui combination could exacerbate Gansui induced GI tract injury. Moreover, the impact of Gancao-Gansui combination to gut microbiota and related metabolism pathways were evaluated. Normal mice were divided into different groups and treated with Gancao extracts, Gansui extracts, and Gancao-Gansui combination extracts for 7 days. Serum biomarkers (diamine oxidase activity, lipopolysaccharide, motilin, IL-1β, IL-6, TNF-α) were determined to reflect GI tract damage. Gut microbiota diversity was studied by 16S rDNA sequencing and metagenomes analysis were also conducted to reflect functional genes expression alteration. Fecal hydrogen sulfide concentrations were measured by spectrophotometry to confirm the alteration of Desulfovibrio genus. Fecal lipid metabolomics study was conducted by GC-MS analysis to confirm the change of metagenomes and Mycoplasma abundance. Gancao-Gansui combination did not exacerbate GI tract tissue or functional damage but caused gut microbiota dysbiosis and increased some rare genus's abundance including Desulfovibrio and Mycoplasma. Desulfovibrio genus proliferation was confirmed by the disturbance of fecal hydrogen sulfide homeostasis. Gancao-Gansui combination also dys-regulated the metabolic genes in metagenomes. Mycoplasma genus proliferation and the metagenomes

  1. Chronic obstructive pulmonary disease candidate gene prioritization based on metabolic networks and functional information.

    Xinyan Wang

    Full Text Available Chronic obstructive pulmonary disease (COPD is a multi-factor disease, in which metabolic disturbances played important roles. In this paper, functional information was integrated into a COPD-related metabolic network to assess similarity between genes. Then a gene prioritization method was applied to the COPD-related metabolic network to prioritize COPD candidate genes. The gene prioritization method was superior to ToppGene and ToppNet in both literature validation and functional enrichment analysis. Top-ranked genes prioritized from the metabolic perspective with functional information could promote the better understanding about the molecular mechanism of this disease. Top 100 genes might be potential markers for diagnostic and effective therapies.

  2. Metabolic parameters and cognitive function in a cohort of older diabetic patients.

    Herghelegiu, Anna Marie; Nacu, Raluca Mihaela; Prada, Gabriel Ioan

    2016-12-01

    Dementia is one of the most disabling conditions associated with old age. With increasing life expectancy, prevalence of both dementia and diabetes is rising. The complex pathological relationship between diabetes mellitus (DM) and dementia has been studied, but is not yet fully understood. The main objective of this study was to investigate the relationship between metabolic parameters and the cognitive function in older diabetics. A total number of 360 diabetic subjects, age 65 years and over, and 300 older people controls were included. Clinical and biological parameters, together with the cognitive function, were assessed every 6 months over a 18-month period, for each study participant. By employing a multivariate linear regression analysis, several significant relationships have been identified: between Clock Drawing Test (CDT) scores and HbA1c (R 2  = 0.68); between CDT scores (R 2  = 0.51) and overall MMSE scores (R 2  = 0.43) on one hand, and DM duration in years, on the other hand; also between CDT scores and BMI (R 2  = 0.59). There was no significant association between fasting serum glucose (FSG), total serum cholesterol, LDL cholesterol or triglycerides levels and cognitive function scores (p > 0.05). The close detailed monitoring of the cognitive function and a rigorous metabolic control are important, especially in the very early stages of DM. Addressing factors such as weight control in older diabetic patients could contribute to better cognitive outcomes.

  3. Metabolic and demographic feedbacks shape the emergent spatial structure and function of microbial communities.

    Sylvie Estrela

    Full Text Available Microbes are predominantly found in surface-attached and spatially structured polymicrobial communities. Within these communities, microbial cells excrete a wide range of metabolites, setting the stage for interspecific metabolic interactions. The links, however, between metabolic and ecological interactions (functional relationships, and species spatial organization (structural relationships are still poorly understood. Here, we use an individual-based modelling framework to simulate the growth of a two-species surface-attached community where food (resource is traded for detoxification (service and investigate how metabolic constraints of individual species shape the emergent structural and functional relationships of the community. We show that strong metabolic interdependence drives the emergence of mutualism, robust interspecific mixing, and increased community productivity. Specifically, we observed a striking and highly stable emergent lineage branching pattern, generating a persistent lineage mixing that was absent when the metabolic exchange was removed. These emergent community properties are driven by demographic feedbacks, such that aid from neighbouring cells directly enhances focal cell growth, which in turn feeds back to neighbour fecundity. In contrast, weak metabolic interdependence drives conflict (exploitation or competition, and in turn greater interspecific segregation. Together, these results support the idea that species structural and functional relationships represent the net balance of metabolic interdependencies.

  4. Reversible changes in brain glucose metabolism following thyroid function normalization in hyperthyroidism.

    Miao, Q; Zhang, S; Guan, Y H; Ye, H Y; Zhang, Z Y; Zhang, Q Y; Xue, R D; Zeng, M F; Zuo, C T; Li, Y M

    2011-01-01

    Patients with hyperthyroidism frequently present with regional cerebral metabolic changes, but the consequences of endocrine-induced brain changes after thyroid function normalization are unclear. We hypothesized that the changes of regional cerebral glucose metabolism are related to thyroid hormone levels in patients with hyperthyroid, and some of these changes can be reversed with antithyroid therapy. Relative regional cerebral glucose metabolism was compared between 10 new-onset untreated patients with hyperthyroidism and 20 healthy control participants by using brain FDG-PET scans. Levels of emotional distress were evaluated by using the SAS and SDS. Patients were treated with methimazole. A follow-up PET scan was performed to assess metabolic changes of the brain when thyroid functions normalized. Compared with controls, patients exhibited lower activity in the limbic system, frontal lobes, and temporal lobes before antithyroid treatment. There were positive correlations between scores of depression and regional metabolism in the cingulate and paracentral lobule. The severity of depression and anxiety covaried negatively with pretreatment activity in the inferior temporal and inferior parietal gyri respectively. Compared with the hyperthyroid status, patients with normalized thyroid functions showed an increased metabolism in the left parahippocampal, fusiform, and right superior frontal gyri. The decrease in both FT3 and FT4 was associated with increased activity in the left parahippocampal and right superior frontal gyri. The changes of regional cerebral glucose metabolism are related to thyroid hormone levels in patients with hyperthyroidism, and some cerebral hypometabolism can be improved after antithyroid therapy.

  5. Optimisation of chromatographic resolution using objective functions including both time and spectral information.

    Torres-Lapasió, J R; Pous-Torres, S; Ortiz-Bolsico, C; García-Alvarez-Coque, M C

    2015-01-16

    The optimisation of the resolution in high-performance liquid chromatography is traditionally performed attending only to the time information. However, even in the optimal conditions, some peak pairs may remain unresolved. Such incomplete resolution can be still accomplished by deconvolution, which can be carried out with more guarantees of success by including spectral information. In this work, two-way chromatographic objective functions (COFs) that incorporate both time and spectral information were tested, based on the peak purity (analyte peak fraction free of overlapping) and the multivariate selectivity (figure of merit derived from the net analyte signal) concepts. These COFs are sensitive to situations where the components that coelute in a mixture show some spectral differences. Therefore, they are useful to find out experimental conditions where the spectrochromatograms can be recovered by deconvolution. Two-way multivariate selectivity yielded the best performance and was applied to the separation using diode-array detection of a mixture of 25 phenolic compounds, which remained unresolved in the chromatographic order using linear and multi-linear gradients of acetonitrile-water. Peak deconvolution was carried out using the combination of orthogonal projection approach and alternating least squares. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Pulmonary Function After Treatment for Embryonal Brain Tumors on SJMB03 That Included Craniospinal Irradiation

    Green, Daniel M.; Merchant, Thomas E.; Billups, Catherine A.; Stokes, Dennis C.; Broniscer, Alberto; Bartels, Ute; Chintagumpala, Murali; Hassall, Timothy E.; Gururangan, Sridharan; McCowage, Geoffrey B.; Heath, John A.; Cohn, Richard J.; Fisher, Michael J.; Srinivasan, Ashok; Robinson, Giles W.; Gajjar, Amar

    2015-01-01

    Purpose: The treatment of children with embryonal brain tumors (EBT) includes craniospinal irradiation (CSI). There are limited data regarding the effect of CSI on pulmonary function. Methods: Protocol SJMB03 enrolled patients 3 to 21 years of age with EBT. Pulmonary function tests (PFTs) (forced expiratory volume in 1 second [FEV 1 ] and forced vital capacity [FVC] by spirometry, total lung capacity [TLC] by nitrogen washout or plethysmography, and diffusing capacity of the lung for carbon monoxide corrected for hemoglobin [DLCO corr ]) were obtained. Differences between PFTs obtained immediately after the completion of CSI and 24 or 60 months after the completion of treatment (ACT) were compared using exact Wilcoxon signed-rank tests and repeated-measures models. Results: Between June 24, 2003, and March 1, 2010, 303 eligible patients (spine dose: ≤2345 cGy, 201; >2345 cGy, 102; proton beam, 20) were enrolled, 260 of whom had at least 1 PFT. The median age at diagnosis was 8.9 years (range, 3.1-20.4 years). The median thoracic spinal radiation dose was 23.4 Gy (interquartile range [IQR], 23.4-36.0 Gy). The median cyclophosphamide dose was 16.0 g/m 2 (IQR, 15.7-16.0 g/m 2 ). At 24 and 60 months ACT, DLCO corr was <75% predicted in 23% (27/118) and 25% (21/84) of patients, FEV 1 was <80% predicted in 20% (34/170) and 29% (32/109) of patients, FVC was <80% predicted in 27% (46/172) and 28% (30/108) of patients, and TLC was <75% predicted in 9% (13/138) and 11% (10/92) of patients. DLCO corr was significantly decreased 24 months ACT (median difference [MD] in % predicted, 3.00%; P=.028) and 60 months ACT (MD in % predicted, 6.00%; P=.033) compared with the end of radiation therapy. These significant decreases in DLCO corr were also observed in repeated-measures models (P=.011 and P=.032 at 24 and 60 months ACT, respectively). Conclusions: A significant minority of EBT survivors experience PFT deficits after CSI. Continued monitoring of this cohort

  7. Pulmonary Function After Treatment for Embryonal Brain Tumors on SJMB03 That Included Craniospinal Irradiation

    Green, Daniel M., E-mail: daniel.green@stjude.org [Department of Epidemiology and Cancer Control, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Merchant, Thomas E. [Department of Radiological Sciences, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Billups, Catherine A. [Department of Biostatistics, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Stokes, Dennis C. [Department of Pediatrics, University of Tennessee School of Medicine, Memphis, Tennessee (United States); Broniscer, Alberto [Department of Oncology, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Bartels, Ute [Department of Haematology and Oncology, The Hospital for Sick Children, Toronto, Ontario (Canada); Chintagumpala, Murali [Department of Pediatric Medicine, Texas Children' s Cancer and Hematology Centers, Baylor College of Medicine, Houston, Texas (United States); Hassall, Timothy E. [Department of Haematology and Oncology, Royal Children' s Hospital, Brisbane (Australia); Gururangan, Sridharan [Department of Pediatrics, Duke University Medical Center, Durham, North Carolina (United States); McCowage, Geoffrey B. [Department of Pediatrics, Children' s Hospital at Westmead, Sydney (Australia); Heath, John A. [Children' s Cancer Center, Royal Children' s Hospital Melbourne, Melbourne (Australia); Cohn, Richard J. [Department of Clinical Oncology, Sydney Children' s Hospital, Sydney (Australia); Fisher, Michael J. [Department of Pediatrics, Children' s Hospital of Philadelphia, Philadelphia, Pennsylvania (United States); Srinivasan, Ashok [Department of Bone Marrow Transplantation & Cellular Therapy, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Robinson, Giles W.; Gajjar, Amar [Department of Oncology, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States)

    2015-09-01

    Purpose: The treatment of children with embryonal brain tumors (EBT) includes craniospinal irradiation (CSI). There are limited data regarding the effect of CSI on pulmonary function. Methods: Protocol SJMB03 enrolled patients 3 to 21 years of age with EBT. Pulmonary function tests (PFTs) (forced expiratory volume in 1 second [FEV{sub 1}] and forced vital capacity [FVC] by spirometry, total lung capacity [TLC] by nitrogen washout or plethysmography, and diffusing capacity of the lung for carbon monoxide corrected for hemoglobin [DLCO{sub corr}]) were obtained. Differences between PFTs obtained immediately after the completion of CSI and 24 or 60 months after the completion of treatment (ACT) were compared using exact Wilcoxon signed-rank tests and repeated-measures models. Results: Between June 24, 2003, and March 1, 2010, 303 eligible patients (spine dose: ≤2345 cGy, 201; >2345 cGy, 102; proton beam, 20) were enrolled, 260 of whom had at least 1 PFT. The median age at diagnosis was 8.9 years (range, 3.1-20.4 years). The median thoracic spinal radiation dose was 23.4 Gy (interquartile range [IQR], 23.4-36.0 Gy). The median cyclophosphamide dose was 16.0 g/m{sup 2} (IQR, 15.7-16.0 g/m{sup 2}). At 24 and 60 months ACT, DLCO{sub corr} was <75% predicted in 23% (27/118) and 25% (21/84) of patients, FEV{sub 1} was <80% predicted in 20% (34/170) and 29% (32/109) of patients, FVC was <80% predicted in 27% (46/172) and 28% (30/108) of patients, and TLC was <75% predicted in 9% (13/138) and 11% (10/92) of patients. DLCO{sub corr} was significantly decreased 24 months ACT (median difference [MD] in % predicted, 3.00%; P=.028) and 60 months ACT (MD in % predicted, 6.00%; P=.033) compared with the end of radiation therapy. These significant decreases in DLCO{sub corr} were also observed in repeated-measures models (P=.011 and P=.032 at 24 and 60 months ACT, respectively). Conclusions: A significant minority of EBT survivors experience PFT deficits after CSI

  8. Microbial community assembly and metabolic function during mammalian corpse decomposition

    Metcalf, J. L.; Xu, Z. Z.; Weiss, S.; Lax, S.; Van Treuren, W.; Hyde, E. R.; Song, S. J.; Amir, A.; Larsen, P.; Sangwan, N.; Haarmann, D.; Humphrey, G. C.; Ackermann, G.; Thompson, L. R.; Lauber, C.; Bibat, A.; Nicholas, C.; Gebert, M. J.; Petrosino, J. F.; Reed, S. C.; Gilbert, J. A.; Lynne, A. M.; Bucheli, S. R.; Carter, D. O.; Knight, R.

    2015-12-10

    Vertebrate corpse decomposition provides an important stage in nutrient cycling in most terrestrial habitats, yet microbially mediated processes are poorly understood. Here we combine deep microbial community characterization, community-level metabolic reconstruction, and soil biogeochemical assessment to understand the principles governing microbial community assembly during decomposition of mouse and human corpses on different soil substrates. We find a suite of bacterial and fungal groups that contribute to nitrogen cycling and a reproducible network of decomposers that emerge on predictable time scales. Our results show that this decomposer community is derived primarily from bulk soil, but key decomposers are ubiquitous in low abundance. Soil type was not a dominant factor driving community development, and the process of decomposition is sufficiently reproducible to offer new opportunities for forensic investigations.

  9. Microbial community assembly and metabolic function during mammalian corpse decomposition

    Metcalf, Jessica L; Xu, Zhenjiang Zech; Weiss, Sophie; Lax, Simon; Van Treuren, Will; Hyde, Embriette R.; Song, Se Jin; Amir, Amnon; Larsen, Peter; Sangwan, Naseer; Haarmann, Daniel; Humphrey, Greg C; Ackermann, Gail; Thompson, Luke R; Lauber, Christian; Bibat, Alexander; Nicholas, Catherine; Gebert, Matthew J; Petrosino, Joseph F; Reed, Sasha C.; Gilbert, Jack A; Lynne, Aaron M; Bucheli, Sibyl R; Carter, David O; Knight, Rob

    2016-01-01

    Vertebrate corpse decomposition provides an important stage in nutrient cycling in most terrestrial habitats, yet microbially mediated processes are poorly understood. Here we combine deep microbial community characterization, community-level metabolic reconstruction, and soil biogeochemical assessment to understand the principles governing microbial community assembly during decomposition of mouse and human corpses on different soil substrates. We find a suite of bacterial and fungal groups that contribute to nitrogen cycling and a reproducible network of decomposers that emerge on predictable time scales. Our results show that this decomposer community is derived primarily from bulk soil, but key decomposers are ubiquitous in low abundance. Soil type was not a dominant factor driving community development, and the process of decomposition is sufficiently reproducible to offer new opportunities for forensic investigations.

  10. Blood metabolism study on protection of residual renal function of hemodialysis patients by traditional Chinese medicine Kidney Flaccidity Compound.

    Hu, Qiong-Dan; Wu, Wei-Hua; Zeng, Yan; Wen, Ji; Li, Xiao-Jun; Pan, Wei; Zhang, Mao-Ping; Hu, Bo; Lei, Chun-Yan; Fan, Junming

    2018-04-30

    In recent years, metabolomics using high-performance liquid chromatography (UPLC) has been used to study the metabolic profiles in plasma, urine, stool and tissue in animal model of chronic kidney disease (CKD). In the previous work, we found that traditional Chinese medicine (TCM) "Kidney Flaccidity Compound" (KFC) based on "kidney flaccidity theory" can improve renal function and quality of life of patients with kidney disease. This study aimed to investigate the metabolic profiles in peripheral blood of hemodialysis patients administrated by KFC for 1.5 and 3 months and explore the potential metabolic mechanism using UPLC. Results showed that 121 metabolites were different between KFC 3-months group and untreated control, of which 75 were significantly upregulated and 46 were significantly downregulated. In the 1.5-months treatment group, there were 365 metabolites, of which 164 were significantly upregulated and 192 downregulated. There were 6 metabolites and 15 metabolites upregulated 3-fold in 3-months and 1.5-months KFC treatment group, respectively. In addition, more than 60 new metabolites were identified in the peripheral blood in KFC treated patients, including two potential diagnostic markers MGDG 30:8 and 2-(hydroxymethyl)-6-[[(1R,4S) -2,2,4-trimethyl-3-oxabicyclo[2.2.2]octan-5-yl]oxy]oxane-3,4,5-triol. The pathway enrichment analysis showed thce differential metabolites mainly enriched in Arginine and proline metabolism, Urea cycle, Tyrosine metabolism, Methionine metabolism, Tricarboxylic acid cycle, and Androgen and estrogen metabolism. The findings are helpful to reveal the mechanism of KFC protects CKD, and to provide a new strategy for recovery renal function in hemodialysis patients.

  11. Psychosocial and metabolic function by smoking status in individuals with binge eating disorder and obesity.

    Udo, Tomoko; White, Marney A; Barnes, Rachel D; Ivezaj, Valentina; Morgan, Peter; Masheb, Robin M; Grilo, Carlos M

    2016-02-01

    Individuals with binge eating disorder (BED) report smoking to control appetite and weight. Smoking in BED is associated with increased risk for comorbid psychiatric disorders, but its impact on psychosocial functioning and metabolic function has not been evaluated. Participants were 429 treatment-seeking adults (72.4% women; mean age 46.2±11.0years old) with BED comorbid with obesity. Participants were categorized into current smokers (n=66), former smokers (n=145), and never smokers (n=218). Smoking status was unrelated to most historical eating/weight variables and to current eating disorder psychopathology. Smoking status was associated with psychiatric, psychosocial, and metabolic functioning. Compared with never smokers, current smokers were more likely to meet lifetime diagnostic criteria for alcohol (OR=5.51 [95% CI=2.46-12.33]) and substance use disorders (OR=7.05 [95% CI=3.37-14.72]), poorer current physical quality of life, and increased risk for metabolic syndrome (OR=1.80 [95% CI=0.97-3.35]) and related metabolic risks (reduced HDL, elevated total cholesterol). On the other hand, the odds of meeting criteria for lifetime psychiatric comorbidity or metabolic abnormalities were not significantly greater in former smokers, relative to never smokers. Our findings suggest the importance of promoting smoking cessation in treatment-seeking patients with BED and obesity for its potential long-term implications for psychiatric and metabolic functioning. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Gap-filling analysis of the iJO1366 Escherichia coli metabolic network reconstruction for discovery of metabolic functions

    Orth Jeffrey D

    2012-05-01

    Full Text Available Abstract Background The iJO1366 reconstruction of the metabolic network of Escherichia coli is one of the most complete and accurate metabolic reconstructions available for any organism. Still, because our knowledge of even well-studied model organisms such as this one is incomplete, this network reconstruction contains gaps and possible errors. There are a total of 208 blocked metabolites in iJO1366, representing gaps in the network. Results A new model improvement workflow was developed to compare model based phenotypic predictions to experimental data to fill gaps and correct errors. A Keio Collection based dataset of E. coli gene essentiality was obtained from literature data and compared to model predictions. The SMILEY algorithm was then used to predict the most likely missing reactions in the reconstructed network, adding reactions from a KEGG based universal set of metabolic reactions. The feasibility of these putative reactions was determined by comparing updated versions of the model to the experimental dataset, and genes were predicted for the most feasible reactions. Conclusions Numerous improvements to the iJO1366 metabolic reconstruction were suggested by these analyses. Experiments were performed to verify several computational predictions, including a new mechanism for growth on myo-inositol. The other predictions made in this study should be experimentally verifiable by similar means. Validating all of the predictions made here represents a substantial but important undertaking.

  13. Diversity and functional traits of culturable microbiome members, including cyanobacteria in the rice phyllosphere.

    Venkatachalam, S; Ranjan, K; Prasanna, R; Ramakrishnan, B; Thapa, S; Kanchan, A

    2016-07-01

    The diversity and abundance of culturable microbiome members of the rice phyllosphere was investigated using cv. Pusa Punjab Basmati 1509. Both diversity and species richness of bacteria were significantly higher in plants in pots in a semi-controlled environment than those in fields. Application of fertilisers reduced both diversity and species richness in field-grown plants under a conventional flooded system of rice intensification (SRI) and in dry-seeded rice (DSR) modes. Sequence analyses of 16S rDNA of culturable bacteria, those selected after amplified ribosomal DNA restriction analysis (ARDRA), showed the dominance of α-proteobacteria (35%) and actinobacteria (38%); Pantoea, Exiguobacterium and Bacillus were common among the culturable phyllospheric bacteria. About 34% of 83 culturable bacterial isolates had higher potential (>2 μg·ml(-1) ) for indole acetic acid production in the absence of tryptophan. Interestingly, the phyllosphere bacterial isolates from the pot experiment had significantly higher potential for nitrogen fixation than isolates from the field experiment. Enrichment for cyanobacteria showed both unicellular forms and non-heterocystous filaments under aerobic as well as anaerobic conditions. PCR-DGGE analysis of these showed that aerobic and anaerobic conditions as well as the three modes of cultivation of rice in the field strongly influenced the number and abundance of phylotypes. The adaptability and functional traits of these culturable microbiome members suggest enormous diversity in the phyllosphere, including potential for plant growth promotion, which was also significantly influenced by the different methods of growing rice. © 2016 German Botanical Society and The Royal Botanical Society of the Netherlands.

  14. Red Blood Cell Function and Dysfunction: Redox Regulation, Nitric Oxide Metabolism, Anemia

    Kuhn, Viktoria; Diederich, Lukas; Keller, T.C. Stevenson; Kramer, Christian M.; Lückstädt, Wiebke; Panknin, Christina; Suvorava, Tatsiana; Isakson, Brant E.; Kelm, Malte

    2017-01-01

    Abstract Significance: Recent clinical evidence identified anemia to be correlated with severe complications of cardiovascular disease (CVD) such as bleeding, thromboembolic events, stroke, hypertension, arrhythmias, and inflammation, particularly in elderly patients. The underlying mechanisms of these complications are largely unidentified. Recent Advances: Previously, red blood cells (RBCs) were considered exclusively as transporters of oxygen and nutrients to the tissues. More recent experimental evidence indicates that RBCs are important interorgan communication systems with additional functions, including participation in control of systemic nitric oxide metabolism, redox regulation, blood rheology, and viscosity. In this article, we aim to revise and discuss the potential impact of these noncanonical functions of RBCs and their dysfunction in the cardiovascular system and in anemia. Critical Issues: The mechanistic links between changes of RBC functional properties and cardiovascular complications related to anemia have not been untangled so far. Future Directions: To allow a better understanding of the complications associated with anemia in CVD, basic and translational science studies should be focused on identifying the role of noncanonical functions of RBCs in the cardiovascular system and on defining intrinsic and/or systemic dysfunction of RBCs in anemia and its relationship to CVD both in animal models and clinical settings. Antioxid. Redox Signal. 26, 718–742. PMID:27889956

  15. Functional genomics of lipid metabolism in the oleaginous yeast Rhodosporidium toruloides

    Geiselman, Gina M; Ito, Masakazu; Mondo, Stephen J; Reilly, Morgann C; Cheng, Ya-Fang; Bauer, Stefan; Grigoriev, Igor V; Gladden, John M; Simmons, Blake A; Brem, Rachel B

    2018-01-01

    The basidiomycete yeast Rhodosporidium toruloides (also known as Rhodotorula toruloides) accumulates high concentrations of lipids and carotenoids from diverse carbon sources. It has great potential as a model for the cellular biology of lipid droplets and for sustainable chemical production. We developed a method for high-throughput genetics (RB-TDNAseq), using sequence-barcoded Agrobacterium tumefaciens T-DNA insertions. We identified 1,337 putative essential genes with low T-DNA insertion rates. We functionally profiled genes required for fatty acid catabolism and lipid accumulation, validating results with 35 targeted deletion strains. We identified a high-confidence set of 150 genes affecting lipid accumulation, including genes with predicted function in signaling cascades, gene expression, protein modification and vesicular trafficking, autophagy, amino acid synthesis and tRNA modification, and genes of unknown function. These results greatly advance our understanding of lipid metabolism in this oleaginous species and demonstrate a general approach for barcoded mutagenesis that should enable functional genomics in diverse fungi. PMID:29521624

  16. Metabolic imaging for breast cancer detection and treatment: a role for mitochondrial Complex I function

    Ramanujan, V. Krishnan

    2018-02-01

    Cancer cells are known to display a variety of metabolic reprogramming strategies to fulfill their own growth and proliferative agenda. With the advent of high resolution imaging strategies, metabolomics techniques etc., there is an increasing appreciation of critical role that tumor cell metabolism plays in the overall breast cancer (BC) growth. A recent study from our laboratory demonstrated that the development of invasive cancers could be causally connected to deficits in mitochondrial function. Using this study as a rationale, we hypothesize that the widely accepted multistep tumor growth model might have a strong metabolic component as well. In this study, we explore the possibility of targeting mitochondrial Complex I enzyme system for not only metabolic detection of cancer-associated redox changes but also for modulating breast cancer cell growth characteristics. As a proof-of-principle, we demonstrate two approaches (pharmacological and genetic) for modulating mitochondrial Complex I function so as to achieve breast cancer control.

  17. Molecules in motion: influences of diffusion on metabolic structure and function in skeletal muscle.

    Kinsey, Stephen T; Locke, Bruce R; Dillaman, Richard M

    2011-01-15

    Metabolic processes are often represented as a group of metabolites that interact through enzymatic reactions, thus forming a network of linked biochemical pathways. Implicit in this view is that diffusion of metabolites to and from enzymes is very fast compared with reaction rates, and metabolic fluxes are therefore almost exclusively dictated by catalytic properties. However, diffusion may exert greater control over the rates of reactions through: (1) an increase in reaction rates; (2) an increase in diffusion distances; or (3) a decrease in the relevant diffusion coefficients. It is therefore not surprising that skeletal muscle fibers have long been the focus of reaction-diffusion analyses because they have high and variable rates of ATP turnover, long diffusion distances, and hindered metabolite diffusion due to an abundance of intracellular barriers. Examination of the diversity of skeletal muscle fiber designs found in animals provides insights into the role that diffusion plays in governing both rates of metabolic fluxes and cellular organization. Experimental measurements of metabolic fluxes, diffusion distances and diffusion coefficients, coupled with reaction-diffusion mathematical models in a range of muscle types has started to reveal some general principles guiding muscle structure and metabolic function. Foremost among these is that metabolic processes in muscles do, in fact, appear to be largely reaction controlled and are not greatly limited by diffusion. However, the influence of diffusion is apparent in patterns of fiber growth and metabolic organization that appear to result from selective pressure to maintain reaction control of metabolism in muscle.

  18. Functional analysis of thermostable proteins involved in carbohydrate metabolism

    Akerboom, A.P.

    2007-01-01

    Thermostable proteins can resist temperature stress whilst keeping their integrity and functionality. In many cases, thermostable proteins originate from hyperthermophilic microorganisms that thrive in extreme environments. These systems are generally located close to geothermal (volcanic) activity,

  19. A Cellular Perspective on Brain Energy Metabolism and Functional Imaging

    Magistretti, Pierre J.; Allaman, Igor

    2015-01-01

    The energy demands of the brain are high: they account for at least 20% of the body's energy consumption. Evolutionary studies indicate that the emergence of higher cognitive functions in humans is associated with an increased glucose utilization

  20. Study of beta-cell function (by HOMA model) in metabolic syndrome.

    Garg, M K; Dutta, M K; Mahalle, Namita

    2011-07-01

    The clustering of cardiovascular risk factors is termed the metabolic syndrome (MS), which strongly predict risk of diabetes and cardiovascular disease. Many studies implicate insulin resistance (IR) in the development of diabetes, but ignore the contribution of beta-cell dysfunction. Hence, we studied beta-cell function, as assessed by HOMA model, in subjects with MS. We studied 50 subjects with MS diagnosed by IDF criteria and 24 healthy age- and sex-matched controls. Clinical evaluation included anthropometry, body fat analysis by bioimpedance, biochemical, and insulin measurement. IR and secretion were calculated by HOMA model. Subjects with MS had more IR (HOMA-IR) than controls (3.35 ± 3.14 vs. 1.76 ± 0.53, P = 0.029) and secreted less insulin (HOMA-S) than controls (66.80 ± 69.66 vs. 144.27 ± 101.61, P = 0.0003), although plasma insulin levels were comparable in both groups (10.7 ± 10.2 vs. 8.2 ± 2.38, P = 0.44). HOMA-IR and HOMA-S were related with number of metabolic abnormalities. HOMA-IR was positively associated with body mass index, waist hip ratio, body fat mass, and percent body fat. HOMA-S was negatively associated with waist hip ratio, fasting plasma glucose and total cholesterol and positively with basal metabolic rate. Percent body fat was an independent predictor of HOMA-IR and waist hip ratio of HOMA-S in multiple regression analysis. Subjects with MS have increased IR and decreased insulin secretion compared with healthy controls. Lifestyle measures have been shown to improve IR, insulin secretion, and various components and effects of MS. Hence, there is an urgent need for public health measures to prevent ongoing epidemic of diabetes and cardiovascular disease.

  1. From Network Analysis to Functional Metabolic Modeling of the Human Gut Microbiota.

    Bauer, Eugen; Thiele, Ines

    2018-01-01

    An important hallmark of the human gut microbiota is its species diversity and complexity. Various diseases have been associated with a decreased diversity leading to reduced metabolic functionalities. Common approaches to investigate the human microbiota include high-throughput sequencing with subsequent correlative analyses. However, to understand the ecology of the human gut microbiota and consequently design novel treatments for diseases, it is important to represent the different interactions between microbes with their associated metabolites. Computational systems biology approaches can give further mechanistic insights by constructing data- or knowledge-driven networks that represent microbe interactions. In this minireview, we will discuss current approaches in systems biology to analyze the human gut microbiota, with a particular focus on constraint-based modeling. We will discuss various community modeling techniques with their advantages and differences, as well as their application to predict the metabolic mechanisms of intestinal microbial communities. Finally, we will discuss future perspectives and current challenges of simulating realistic and comprehensive models of the human gut microbiota.

  2. Regulation of metabolic health and adipose tissue function by group 2 innate lymphoid cells.

    Cautivo, Kelly M; Molofsky, Ari B

    2016-06-01

    Adipose tissue (AT) is home to an abundance of immune cells. With chronic obesity, inflammatory immune cells accumulate and promote insulin resistance and the progression to type 2 diabetes mellitus. In contrast, recent studies have highlighted the regulation and function of immune cells in lean, healthy AT, including those associated with type 2 or "allergic" immunity. Although traditionally activated by infection with multicellular helminthes, AT type 2 immunity is active independently of infection, and promotes tissue homeostasis, AT "browning," and systemic insulin sensitivity, protecting against obesity-induced metabolic dysfunction and type 2 diabetes mellitus. In particular, group 2 innate lymphoid cells (ILC2s) are integral regulators of AT type 2 immunity, producing the cytokines interleukin-5 and IL-13, promoting eosinophils and alternatively activated macrophages, and cooperating with and promoting AT regulatory T (Treg) cells. In this review, we focus on the recent developments in our understanding of group 2 innate lymphoid cell cells and type 2 immunity in AT metabolism and homeostasis. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Simultaneous determination of dynamic cardiac metabolism and function using PET/MRI.

    Barton, Gregory P; Vildberg, Lauren; Goss, Kara; Aggarwal, Niti; Eldridge, Marlowe; McMillan, Alan B

    2018-05-01

    Cardiac metabolic changes in heart disease precede overt contractile dysfunction. However, metabolism and function are not typically assessed together in clinical practice. The purpose of this study was to develop a cardiac positron emission tomography/magnetic resonance (PET/MR) stress test to assess the dynamic relationship between contractile function and metabolism in a preclinical model. Following an overnight fast, healthy pigs (45-50 kg) were anesthetized and mechanically ventilated. 18 F-fluorodeoxyglucose ( 18 F-FDG) solution was administered intravenously at a constant rate of 0.01 mL/s for 60 minutes. A cardiac PET/MR stress test was performed using normoxic gas (F I O 2  = .209) and hypoxic gas (F I O 2  = .12). Simultaneous cardiac imaging was performed on an integrated 3T PET/MR scanner. Hypoxic stress induced a significant increase in heart rate, cardiac output, left ventricular (LV) ejection fraction (EF), and peak torsion. There was a significant decline in arterial SpO 2 , LV end-diastolic and end-systolic volumes in hypoxia. Increased LV systolic function was coupled with an increase in myocardial FDG uptake (Ki) during hypoxic stress. PET/MR with continuous FDG infusion captures dynamic changes in both cardiac metabolism and contractile function. This technique warrants evaluation in human cardiac disease for assessment of subtle functional and metabolic abnormalities.

  4. Free fatty acids and their metabolism affect function and survival of podocytes

    Jonas eSieber

    2014-10-01

    Full Text Available Podocyte injury and loss critically contribute to the pathogenesis of proteinuric kidney diseases including diabetic nephropathy. Deregulated lipid metabolism with disturbed free fatty acid (FFA metabolism is a characteristic of metabolically unhealthy obesity and type 2 diabetes and likely contributes to end-stage kidney disease irrespective of the underlying kidney disease. In the current review we summarize recent findings related to FFAs and altered renal FFA metabolism with a special focus on podocytes. We will outline the opposing effects of saturated and monounsaturated FFAs and a particular emphasis will be given to the underlying molecular mechanisms involving insulin resistance and endoplasmic reticulum homeostasis. Finally, recent data suggesting a critical role of renal FFA metabolism to adapt to an altered lipid environment will be discussed.

  5. Functional integration changes in regional brain glucose metabolism from childhood to adulthood.

    Trotta, Nicola; Archambaud, Frédérique; Goldman, Serge; Baete, Kristof; Van Laere, Koen; Wens, Vincent; Van Bogaert, Patrick; Chiron, Catherine; De Tiège, Xavier

    2016-08-01

    The aim of this study was to investigate the age-related changes in resting-state neurometabolic connectivity from childhood to adulthood (6-50 years old). Fifty-four healthy adult subjects and twenty-three pseudo-healthy children underwent [(18) F]-fluorodeoxyglucose positron emission tomography at rest. Using statistical parametric mapping (SPM8), age and age squared were first used as covariate of interest to identify linear and non-linear age effects on the regional distribution of glucose metabolism throughout the brain. Then, by selecting voxels of interest (VOI) within the regions showing significant age-related metabolic changes, a psychophysiological interaction (PPI) analysis was used to search for age-induced changes in the contribution of VOIs to the metabolic activity in other brain areas. Significant linear or non-linear age-related changes in regional glucose metabolism were found in prefrontal cortices (DMPFC/ACC), cerebellar lobules, and thalamo-hippocampal areas bilaterally. Decreases were found in the contribution of thalamic, hippocampal, and cerebellar regions to DMPFC/ACC metabolic activity as well as in the contribution of hippocampi to preSMA and right IFG metabolic activities. Increases were found in the contribution of the right hippocampus to insular cortex and of the cerebellar lobule IX to superior parietal cortex metabolic activities. This study evidences significant linear or non-linear age-related changes in regional glucose metabolism of mesial prefrontal, thalamic, mesiotemporal, and cerebellar areas, associated with significant modifications in neurometabolic connectivity involving fronto-thalamic, fronto-hippocampal, and fronto-cerebellar networks. These changes in functional brain integration likely represent a metabolic correlate of age-dependent effects on sensory, motor, and high-level cognitive functional networks. Hum Brain Mapp 37:3017-3030, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  6. Simultaneous measurements of work function and H‒ density including caesiation of a converter surface

    Cristofaro, S.; Friedl, R.; Fantz, U.

    2017-08-01

    Negative hydrogen ion sources rely on the surface conversion of neutral atomic hydrogen and positive hydrogen ions to H-. The efficiency of this process depends on the actual work function of the converter surface. By introducing caesium into the source the work function decreases, enhancing the negative ion yield. In order to study the impact of the work function on the H- surface production at similar conditions to the ones in ion sources for fusion devices like ITER and DEMO, fundamental investigations are performed in a flexible laboratory experiment. The work function of the converter surface can be absolutely measured by photoelectric effect, while a newly installed cavity ring-down spectroscopy system (CRDS) measures the H- density. The CRDS is firstly tested and characterized by investigations on H- volume production. Caesiation of a stainless steel sample is then performed in vacuum and the plasma effect on the Cs layer is investigated also for long plasma-on times. A minimum work function of (1.9±0.1) eV is reached after some minutes of plasma treatment, resulting in a reduction by a value of 0.8 eV compared to vacuum measurements. The H- density above the surface is (2.1±0.5)×1015 m-3. With further plasma exposure of the caesiated surface, the work function increases up to 3.75 eV, due to the impinging plasma particles which gradually remove the Cs layer. As a result, the H- density decreases by a factor of at least 2.

  7. Metabolic Control of Dendritic Cell Activation and Function: Recent Advances and Clinical Implications

    Bart eEverts

    2014-05-01

    Full Text Available Dendritic cells (DCs are key regulators of both immunity and tolerance by controlling activation and polarization of effector T helper cell and regulatory T cell responses. Therefore, there is a major focus on developing approaches to manipulate DC function for immunotherapy. It is well known that changes in cellular activation are coupled to profound changes in cellular metabolism. Over the past decade there is a growing appreciation that these metabolic changes also underlie the capacity of immune cells to perform particular functions. This has led to the concept that the manipulation of cellular metabolism can be used to shape innate and adaptive immune responses. While most of our understanding in this area has been gained from studies with T cells and macrophages, evidence is emerging that the activation and function of DCs are also dictated by the type of metabolism these cells commit to. We here discuss these new insights and explore whether targeting of metabolic pathways in DCs could hold promise as a novel approach to manipulate the functional properties of DCs for clinical purposes.

  8. Metabolic effects of the iodothyronine functional analogue TRC150094 on the liver and skeletal muscle of high-fat diet fed overweight rats: an integrated proteomic study.

    Silvestri, Elena; Glinni, Daniela; Cioffi, Federica; Moreno, Maria; Lombardi, Assunta; de Lange, Pieter; Senese, Rosalba; Ceccarelli, Michele; Salzano, Anna Maria; Scaloni, Andrea; Lanni, Antonia; Goglia, Fernando

    2012-07-06

    A novel functional iodothyronine analogue, TRC150094, which has a much lower potency toward thyroid hormone receptor (α1/β1) activation than triiodothyronine, has been shown to be effective at reducing adiposity in rats simultaneously receiving a high-fat diet (HFD). Here, by combining metabolic, functional and proteomic analysis, we studied how the hepatic and skeletal muscle phenotypes might respond to TRC150094 treatment in HFD-fed overweight rats. Drug treatment increased both the liver and skeletal muscle mitochondrial oxidative capacities without altering mitochondrial efficiency. Coherently, in terms of individual respiratory in-gel activity, blue-native analysis revealed an increased activity of complex V in the liver and of complexes II and V in tibialis muscle in TCR150094-treated animals. Subsequently, the identification of differentially expressed proteins and the analysis of their interrelations gave an integrated view of the phenotypic/metabolic adaptations occurring in the liver and muscle proteomes during drug treatment. TRC150094 significantly altered the expression of several proteins involved in key liver metabolic pathways, including amino acid and nitrogen metabolism, and fructose and mannose metabolism. The canonical pathways most strongly influenced by TRC150094 in tibialis muscle included glycolysis and gluconeogenesis, amino acid, fructose and mannose metabolism, and cell signaling. The phenotypic/metabolic influence of TRC150094 on the liver and skeletal muscle of HFD-fed overweight rats suggests the potential clinical application of this iodothyronine analogue in ameliorating metabolic risk parameters altered by diet regimens.

  9. Evidence for compromised metabolic function and limited glucose uptake in spermatozoa from the teratospermic domestic cat (Felis catus) and cheetah (Acinonyx jubatus).

    Terrell, Kimberly A; Wildt, David E; Anthony, Nicola M; Bavister, Barry D; Leibo, Stanley P; Penfold, Linda M; Marker, Laurie L; Crosier, Adrienne E

    2010-11-01

    Cheetahs and certain other felids consistently ejaculate high proportions (≥ 60%) of malformed spermatozoa, a condition known as teratospermia, which is prevalent in humans. Even seemingly normal spermatozoa from domestic cat teratospermic ejaculates have reduced fertilizing capacity. To understand the role of sperm metabolism in this phenomenon, we conducted a comparative study in the normospermic domestic cat versus the teratospermic cat and cheetah with the general hypothesis that sperm metabolic function is impaired in males producing predominantly pleiomorphic spermatozoa. Washed ejaculates were incubated in chemically defined medium containing glucose and pyruvate. Uptake of glucose and pyruvate and production of lactate were assessed using enzyme-linked fluorescence assays. Spermatozoa from domestic cats and cheetahs exhibited similar metabolic profiles, with minimal glucose metabolism and approximately equimolar rates of pyruvate uptake and lactate production. Compared to normospermic counterparts, pyruvate and lactate metabolism were reduced in teratospermic cat and cheetah ejaculates, even when controlling for sperm motility. Rates of pyruvate and lactate (but not glucose) metabolism were correlated positively with sperm motility, acrosomal integrity, and normal morphology. Collectively, our findings reveal that pyruvate uptake and lactate production are reliable, quantitative indicators of sperm quality in these two felid species and that metabolic function is impaired in teratospermic ejaculates. Furthermore, patterns of substrate utilization are conserved between these species, including the unexpected lack of exogenous glucose metabolism. Because glycolysis is required to support sperm motility and capacitation in certain other mammals (including dogs), the activity of this pathway in felid spermatozoa is a target for future investigation.

  10. Beta-cell function is associated with metabolic syndrome in Mexican subjects

    Pérez-Fuentes

    2010-08-01

    Full Text Available Blanca G Baez-Duarte1,3, María Del Carmen Sánchez-Guillén3†, Ricardo Pérez-Fuentes2,3, Irma Zamora-Ginez1,3, Bertha Alicia Leon-Chavez1, Cristina Revilla-Monsalve4, Sergio Islas-Andrade41Posgrado en Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, México; 2Facultad de Medicina, Benemérita Universidad Autónoma de Puebla, México; 3Centro de Investigación Biomédica de Oriente, Instituto Mexicano del Seguro Social, Atlixco, Puebla, México; 4Multidiciplinary Research Group on Diabetes (José Sánchez-Corona, Fernando Guerrero-Romero, Martha Rodriguez-Moran, Agustin Madero, Jorge Escobedo-de-la-Peña, Silvia Flores-Martinez, Esperanza, Martinez-Abundis, Manuel Gonzalez-Ortiz, Alberto Rascon-Pacheco, Margarita Torres-Tamayo, Instituto Mexicano del Seguro Social, México, Distrito Federal, México; †María Del Carmen Sánchez-Guillén passed away on 27 November 2009.Aims: The clinical diagnosis of metabolic syndrome does not find any parameters to evaluate the insulin sensitivity (IS or β-cell function. The evaluation of these parameters would detect early risk of developing metabolic syndrome. The aim of this study is to determine the relationship between β-cell function and presence of metabolic syndrome in Mexican subjects.Material and methods: This study is part of the Mexican Survey on the Prevention of Diabetes (MexDiab Study with headquarters in the city of Puebla, Mexico. The study comprised of 444 subjects of both genders, aged between 18 and 60 years and allocated into two study groups: (1 control group of individuals at metabolic balance without metabolic syndrome and (2 group composed of subjects with metabolic syndrome and diagnosed according to the criteria of the Third Report of the National Cholesterol Education Program Expert Panel on Defection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Anthropometric, biochemical, and clinical assessments were carried out.Results: Average age of the

  11. Mitochondrial biogenesis and energy production in differentiating murine stem cells: a functional metabolic study.

    Han, Sungwon; Auger, Christopher; Thomas, Sean C; Beites, Crestina L; Appanna, Vasu D

    2014-02-01

    The significance of metabolic networks in guiding the fate of the stem cell differentiation is only beginning to emerge. Oxidative metabolism has been suggested to play a major role during this process. Therefore, it is critical to understand the underlying mechanisms of metabolic alterations occurring in stem cells to manipulate the ultimate outcome of these pluripotent cells. Here, using P19 murine embryonal carcinoma cells as a model system, the role of mitochondrial biogenesis and the modulation of metabolic networks during dimethyl sulfoxide (DMSO)-induced differentiation are revealed. Blue native polyacrylamide gel electrophoresis (BN-PAGE) technology aided in profiling key enzymes, such as hexokinase (HK) [EC 2.7.1.1], glucose-6-phosphate isomerase (GPI) [EC 5.3.1.9], pyruvate kinase (PK) [EC 2.7.1.40], Complex I [EC 1.6.5.3], and Complex IV [EC 1.9.3.1], that are involved in the energy budget of the differentiated cells. Mitochondrial adenosine triphosphate (ATP) production was shown to be increased in DMSO-treated cells upon exposure to the tricarboxylic acid (TCA) cycle substrates, such as succinate and malate. The increased mitochondrial activity and biogenesis were further confirmed by immunofluorescence microscopy. Collectively, the results indicate that oxidative energy metabolism and mitochondrial biogenesis were sharply upregulated in DMSO-differentiated P19 cells. This functional metabolic and proteomic study provides further evidence that modulation of mitochondrial energy metabolism is a pivotal component of the cellular differentiation process and may dictate the final destiny of stem cells.

  12. Impact of social integration on metabolic functions: evidence from a nationally representative longitudinal study of US older adults.

    Yang, Yang Claire; Li, Ting; Ji, Yinchun

    2013-12-20

    Metabolic functions may operate as important biophysiological mechanisms through which social relationships affect health. It is unclear how social embeddedness or the lack thereof is related to risk of metabolic dysregulation. To fill this gap we tested the effects of social integration on metabolic functions over time in a nationally representative sample of older adults in the United States and examined population heterogeneity in the effects. Using longitudinal data from 4,323 adults aged over 50 years in the Health and Retirement Study and latent growth curve models, we estimated the trajectories of social integration spanning five waves, 1998-2006, in relation to biomarkers of energy metabolism in 2006. We assessed social integration using a summary index of the number of social ties across five domains. We examined six biomarkers, including total cholesterol, high-density lipoprotein cholesterol, glycosylated hemoglobin, waist circumference, and systolic and diastolic blood pressure, and the summary index of the overall burden of metabolic dysregulation. High social integration predicted significantly lower risks of both individual and overall metabolic dysregulation. Specifically, adjusting for age, sex, race, and body mass index, having four to five social ties reduced the risks of abdominal obesity by 61% (odds ratio [OR] [95% confidence interval {CI}] = 0.39 [0.23, 0.67], p = .007), hypertension by 41% (OR [95% CI] = 0.59 [0.42, 0.84], p = .021), and the overall metabolic dysregulation by 46% (OR [95% CI] = 0.54 [0.40, 0.72], p < .001). The OR for the overall burden remained significant when adjusting for social, behavioral, and illness factors. In addition, stably high social integration had more potent metabolic impacts over time than changes therein. Such effects were consistent across subpopulations and more salient for the younger old (those under age 65), males, whites, and the socioeconomically disadvantaged. This study

  13. Hydrogen sulfide metabolism regulates endothelial solute barrier function

    Shuai Yuan

    2016-10-01

    Full Text Available Hydrogen sulfide (H2S is an important gaseous signaling molecule in the cardiovascular system. In addition to free H2S, H2S can be oxidized to polysulfide which can be biologically active. Since the impact of H2S on endothelial solute barrier function is not known, we sought to determine whether H2S and its various metabolites affect endothelial permeability. In vitro permeability was evaluated using albumin flux and transendothelial electrical resistance. Different H2S donors were used to examine the effects of exogenous H2S. To evaluate the role of endogenous H2S, mouse aortic endothelial cells (MAECs were isolated from wild type mice and mice lacking cystathionine γ-lyase (CSE, a predominant source of H2S in endothelial cells. In vivo permeability was evaluated using the Miles assay. We observed that polysulfide donors induced rapid albumin flux across endothelium. Comparatively, free sulfide donors increased permeability only with higher concentrations and at later time points. Increased solute permeability was associated with disruption of endothelial junction proteins claudin 5 and VE-cadherin, along with enhanced actin stress fiber formation. Importantly, sulfide donors that increase permeability elicited a preferential increase in polysulfide levels within endothelium. Similarly, CSE deficient MAECs showed enhanced solute barrier function along with reduced endogenous bound sulfane sulfur. CSE siRNA knockdown also enhanced endothelial junction structures with increased claudin 5 protein expression. In vivo, CSE genetic deficiency significantly blunted VEGF induced hyperpermeability revealing an important role of the enzyme for barrier function. In summary, endothelial solute permeability is critically regulated via exogenous and endogenous sulfide bioavailability with a prominent role of polysulfides.

  14. Mutagenicity of silver nanoparticles in CHO cells dependent on particle surface functionalization and metabolic activation

    Guigas, Claudia; Walz, Elke; Gräf, Volker; Heller, Knut J.; Greiner, Ralf

    2017-06-01

    The potential of engineered nanomaterials to induce genotoxic effects is an important aspect of hazard identification. In this study, cytotoxicity and mutagenicity as a function of metabolic activation of three silver nanoparticle (AgNP) preparations differing in surface coating were determined in Chinese hamster ovary (CHO) subclone K1 cells. Three silver nanoparticle preparations ( x 90,0 culture medium containing 10% fetal calf serum (FCS) than in medium without FCS. The HPRT test without metabolic activation system S9 revealed that compared to the other AgNP formulations, citrate-coated Ag showed a lower genotoxic effect. However, addition of S9 increased the mutation frequency of all AgNPs and especially influenced the genotoxicity of Citrate-Ag. The results showed that exogenous metabolic activation of nanosilver is crucial even if interactions of the metabolic activation system, nanosilver, and cells are not really understood up to now.

  15. Functional Role of PPARs in Ruminants: Potential Targets for Fine-Tuning Metabolism during Growth and Lactation

    Chen, Shuowen; Khan, Muhammad J.; Loor, Juan J.

    2013-01-01

    Characterization and biological roles of the peroxisome proliferator-activated receptor (PPAR) isotypes are well known in monogastrics, but not in ruminants. However, a wealth of information has accumulated in little more than a decade on ruminant PPARs including isotype tissue distribution, response to synthetic and natural agonists, gene targets, and factors affecting their expression. Functional characterization demonstrated that, as in monogastrics, the PPAR isotypes control expression of genes involved in lipid metabolism, anti-inflammatory response, development, and growth. Contrary to mouse, however, the PPARγ gene network appears to controls milk fat synthesis in lactating ruminants. As in monogastrics, PPAR isotypes in ruminants are activated by long-chain fatty acids, therefore, making them ideal candidates for fine-tuning metabolism in this species via nutrients. In this regard, using information accumulated in ruminants and monogastrics, we propose a model of PPAR isotype-driven biological functions encompassing key tissues during the peripartal period in dairy cattle. PMID:23737762

  16. The association between the metabolic syndrome and metabolic syndrome score and pulmonary function in non-smoking adults.

    Yoon, Hyun; Gi, Mi Young; Cha, Ju Ae; Yoo, Chan Uk; Park, Sang Muk

    2018-03-01

    This study assessed the association of metabolic syndrome and metabolic syndrome score with the predicted forced vital capacity and predicted forced expiratory volume in 1 s (predicted forced expiratory volume in 1 s) values in Korean non-smoking adults. We analysed data obtained from 6684 adults during the 2013-2015 Korean National Health and Nutrition Examination Survey. After adjustment for related variables, metabolic syndrome ( p metabolic syndrome score ( p metabolic syndrome score with metabolic syndrome score 0 as a reference group showed no significance for metabolic syndrome score 1 [1.061 (95% confidence interval, 0.755-1.490)] and metabolic syndrome score 2 [1.247 (95% confidence interval, 0.890-1.747)], but showed significant for metabolic syndrome score 3 [1.433 (95% confidence interval, 1.010-2.033)] and metabolic syndrome score ⩾ 4 [1.760 (95% confidence interval, 1.216-2.550)]. In addition, the odds ratio of restrictive pulmonary disease of the metabolic syndrome [1.360 (95% confidence interval, 1.118-1.655)] was significantly higher than those of non-metabolic syndrome. Metabolic syndrome and metabolic syndrome score were inversely associated with the predicted forced vital capacity and forced expiratory volume in 1 s values in Korean non-smoking adults. In addition, metabolic syndrome and metabolic syndrome score were positively associated with the restrictive pulmonary disease.

  17. Structural, Functional, and Metabolic Brain Markers Differentiate Collision versus Contact and Non-Contact Athletes.

    Churchill, Nathan W; Hutchison, Michael G; Di Battista, Alex P; Graham, Simon J; Schweizer, Tom A

    2017-01-01

    There is growing concern about how participation in contact sports affects the brain. Retrospective evidence suggests that contact sports are associated with long-term negative health outcomes. However, much of the research to date has focused on former athletes with significant health problems. Less is known about the health of current athletes in contact and collision sports who have not reported significant medical issues. In this cross-sectional study, advanced magnetic resonance imaging (MRI) was used to evaluate multiple aspects of brain physiology in three groups of athletes participating in non-contact sports ( N  = 20), contact sports ( N  = 22), and collision sports ( N  = 23). Diffusion tensor imaging was used to assess white matter microstructure based on measures of fractional anisotropy (FA) and mean diffusivity (MD); resting-state functional MRI was used to evaluate global functional connectivity; single-voxel spectroscopy was used to compare ratios of neural metabolites, including N -acetyl aspartate (NAA), creatine (Cr), choline, and myo-inositol. Multivariate analysis revealed structural, functional, and metabolic measures that reliably differentiated between sport groups. The collision group had significantly elevated FA and reduced MD in white matter, compared to both contact and non-contact groups. In contrast, the collision group showed significant reductions in functional connectivity and the NAA/Cr metabolite ratio, relative to only the non-contact group, while the contact group overlapped with both non-contact and collision groups. For brain regions associated with contact sport participation, athletes with a history of concussion also showed greater alterations in FA and functional connectivity, indicating a potential cumulative effect of both contact exposure and concussion history on brain physiology. These findings indicate persistent differences in brain physiology for athletes participating in contact and collision sports

  18. Effects of anabolic hormones on structural, metabolic and functional aspects of skeletal muscle

    Flávio de Oliveira Pires

    2009-01-01

    Full Text Available http://dx.doi.org/10.5007/1980-0037.2009v11n3p350   This study reviewed information regarding the effects of anabolic hormones on strength gain and muscle hypertrophy, emphasizing the physiological mechanisms that may increase muscle strength. Structural, metabolic and functional aspects were analyzed and special attention was paid to the dose-response relationship. The Pubmed database was searched and studies were selected according to relevance and date of publication (last 15 years. The administration of high testosterone doses (~600 mg/week potentiates the effects of strength training, increasing lean body mass, muscle fiber type IIA and IIB cross-sectional area, and the number of myonuclei. There is no evidence of conversion between MHC isoforms. The interaction between testosterone administration and strength training seems to modify some metabolic pathways, increasing protein synthesis, glycogen and ATP-CP muscle stores and improving fat mobilization. Changes in 17-estradiol concentration or in the ACTH-cortisol and insulin-glucagon ratios seem to be associated with these metabolic alterations. Regarding performance, testosterone administration may improve muscle strength by 5-20% depending on the dose used. On the other hand, the effects of growth hormone on the structural and functional aspects of skeletal muscle are not evident, with this hormone more affecting metabolic aspects. However, strictly controlled human studies are necessary to establish the extent of the effects of anabolic hormones on structural, metabolic and functional aspects.

  19. Effects of anabolic hormones on structural, metabolic and functional aspects of skeletal muscle

    Flávio de Oliveira Pires

    2009-06-01

    Full Text Available This study reviewed information regarding the effects of anabolic hormones on strength gain and muscle hypertrophy, emphasizing the physiological mechanisms that may increase muscle strength. Structural, metabolic and functional aspects were analyzed and special attention was paid to the dose-response relationship. The Pubmed database was searched and studies were selected according to relevance and date of publication (last 15 years. The administration of high testosterone doses (~600 mg/week potentiates the effects of strength training, increasing lean body mass, muscle fiber type IIA and IIB cross-sectional area, and the number of myonuclei. There is no evidence of conversion between MHC isoforms. The interaction between testosterone administration and strength training seems to modify some metabolic pathways, increasing protein synthesis, glycogen and ATP-CP muscle stores and improving fat mobilization. Changes in 17-estradiol concentration or in the ACTH-cortisol and insulin-glucagon ratios seem to be associated with these metabolic alterations. Regarding performance, testosterone administration may improve muscle strength by 5-20% depending on the dose used. On the other hand, the effects of growth hormone on the structural and functional aspects of skeletal muscle are not evident, with this hormone more affecting metabolic aspects. However, strictly controlled human studies are necessary to establish the extent of the effects of anabolic hormones on structural, metabolic and functional aspects.

  20. Sex-Specific Effects of Organophosphate Diazinon on the Gut Microbiome and Its Metabolic Functions.

    Gao, Bei; Bian, Xiaoming; Mahbub, Ridwan; Lu, Kun

    2017-02-01

    There is growing recognition of the significance of the gut microbiome to human health, and the association between a perturbed gut microbiome with human diseases has been established. Previous studies also show the role of environmental toxicants in perturbing the gut microbiome and its metabolic functions. The wide agricultural use of diazinon, an organophosphate insecticide, has raised serious environmental health concerns since it is a potent neurotoxicant. With studies demonstrating the presence of a microbiome-gut-brain axis, it is possible that gut microbiome perturbation may also contribute to diazinon toxicity. We investigated the impact of diazinon exposure on the gut microbiome composition and its metabolic functions in C57BL/6 mice. We used a combination of 16S rRNA gene sequencing, metagenomics sequencing, and mass spectrometry-based metabolomics profiling in a mouse model to examine the functional impact of diazinon on the gut microbiome. 16S rRNA gene sequencing revealed that diazinon exposure significantly perturbed the gut microbiome, and metagenomic sequencing found that diazinon exposure altered the functional metagenome. Moreover, metabolomics profiling revealed an altered metabolic profile arising from exposure. Of particular significance, these changes were more pronounced for male mice than for female mice. Diazinon exposure perturbed the gut microbiome community structure, functional metagenome, and associated metabolic profiles in a sex-specific manner. These findings may provide novel insights regarding perturbations of the gut microbiome and its functions as a potential new mechanism contributing to diazinon neurotoxicity and, in particular, its sex-selective effects. Citation: Gao B, Bian X, Mahbub R, Lu K. 2017. Sex-specific effects of organophosphate diazinon on the gut microbiome and its metabolic functions. Environ Health Perspect 125:198-206; http://dx.doi.org/10.1289/EHP202.

  1. Dynamical density functional theory for arbitrary-shape colloidal fluids including inertia and hydrodynamic interactions

    Duran-Olivencia, Miguel A.; Goddard, Ben; Kalliadasis, Serafim

    2015-11-01

    Over the last few decades the classical density-functional theory (DFT) and its dynamic extensions (DDFTs) have become a remarkably powerful tool in the study of colloidal fluids. Recently there has been extensive research to generalise all previous DDFTs finally yielding a general DDFT equation (for spherical particles) which takes into account both inertia and hydrodynamic interactions (HI) which strongly influence non-equilibrium properties. The present work will be devoted to a further generalisation of such a framework to systems of anisotropic particles. To this end, the kinetic equation for the Brownian particle distribution function is derived starting from the Liouville equation and making use of Zwanzig's projection-operator techniques. By averaging over all but one particle, a DDFT equation is finally obtained with some similarities to that for spherical colloids. However, there is now an inevitable translational-rotational coupling which affects the diffusivity of asymmetric particles. Lastly, in the overdamped (high friction) limit the theory is notably simplified leading to a DDFT equation which agrees with previous derivations. We acknowledge financial support from European Research Council via Advanced Grant No. 247031.

  2. Cognitive functions in middle aged individuals are related to metabolic disturbances and aerobic capacity: a cross-sectional study.

    Maria Pedersen

    Full Text Available AIMS: Metabolic disturbances may contribute to cognitive dysfunction in patients with type 2 diabetes. We investigated the relation between cognitive impairment and metabolic deteriorations, low physical fitness, low-grade inflammation and abdominal obesity in middle aged individuals. METHODS: We conducted a cross-sectional study including 40 to 65 year-old patients with type 2 diabetes and limited co morbidity (N = 56, age-matched individuals with impaired glucose tolerance (N = 56 as well as age-matched controls with normal glucose tolerance (N = 72. Specific cognitive functions were assessed with focus on verbal memory, processing speed, executive functions, and a composite overall mean score. Oral glucose tolerance test, VO(2max test, systemic inflammation, DXA scanning and abdominal MRI were measured. RESULTS: Multiple linear regression analyses adjusting for age, gender and verbal intelligence demonstrated that a low score in processing speed, executive functions and overall cognitive function were related to high fasting C-peptide, as well as low insulin sensitivity, beta-cell function and VO(2max. Measurements of blood glucose, obesity and inflammation were not associated with cognitive function. CONCLUSION: Low cognitive scores are seen in middle aged individuals with hyperinsulinemia, low insulin sensitivity, beta-cell function and low aerobic capacity. These findings emphasize the importance of appropriate lifestyle and not only blood glucose control in prevention of cognitive disability.

  3. Pancreatic Function, Type 2 Diabetes, and Metabolism in Aging

    Zhenwei Gong

    2012-01-01

    Full Text Available Aging is a risk factor for impaired glucose tolerance and diabetes. Of the reported 25.8 million Americans estimated to have diabetes, 26.9% are over the age of 65. In certain ethnic groups, the proportion is even higher; almost 1 in 3 older Hispanics and African Americans and 3 out of 4 Pima Indian elders have diabetes. As per the NHANES III (Third National Health and Nutrition Examination survey, the percentage of physician-diagnosed diabetes increased from 3.9% in middle-aged adults (40–49 years to 13.2% in elderly adults (≥75 years. The higher incidence of diabetes is especially alarming considering that diabetes in itself increases the risk for multiple other age-related diseases such as cancer, stroke, cardiovascular diseases, Parkinson’s disease, and Alzheimer’s disease (AD. In this review, we summarize the current evidence on how aging affects pancreatic β cell function, β cell mass, insulin secretion and insulin sensitivity. We also review the effects of aging on the relationship between insulin sensitivity and insulin secretion. Understanding the mechanisms that lead to impaired glucose homeostasis and T2D in the elderly will lead to development of novel treatments that will prevent or delay diabetes, substantially improve quality of life and ultimately increase overall life span.

  4. Beyond triglyceride synthesis: the dynamic functional roles of MGAT and DGAT enzymes in energy metabolism.

    Shi, Yuguang; Cheng, Dong

    2009-07-01

    Monoacyglycerol acyltransferases (MGATs) and diacylglycerol acyltransferases (DGATs) catalyze two consecutive steps of enzyme reactions in the synthesis of triacylglycerols (TAGs). The metabolic complexity of TAG synthesis is reflected by the presence of multiple isoforms of MGAT and DGAT enzymes that differ in catalytic properties, subcellular localization, tissue distribution, and physiological functions. MGAT and DGAT enzymes play fundamental roles in the metabolism of monoacylglycerol (MAG), diacylglycerol (DAG), and triacylglycerol (TAG) that are involved in many aspects of physiological functions, such as intestinal fat absorption, lipoprotein assembly, adipose tissue formation, signal transduction, satiety, and lactation. The recent progress in the phenotypic characterization of mice deficient in MGAT and DGAT enzymes and the development of chemical inhibitors have revealed important roles of these enzymes in the regulation of energy homeostasis and insulin sensitivity. Consequently, selective inhibition of MGAT or DGAT enzymes by synthetic compounds may provide novel treatment for obesity and its related metabolic complications.

  5. Effects of anesthesia on renal function and metabolism in rats assessed by hyperpolarized MRI

    Qi, Haiyun; Mariager, Christian Østergaard; Lindhardt, Jakob

    2018-01-01

    . In the present study, we aimed to investigate the renal functional and metabolic consequences of 3 typical rodent anesthetics used in preclinical MRI: sevoflurane, inaction, and a mixture of fentanyl, fluanisone, and midazolam (FFM). METHODS: The renal effects of 3 different classes of anesthetics (inactin......, servoflurane, and FFM) were investigated using functional and metabolic MRI. The renal glucose metabolism and hemodynamics was characterized with hyperpolarized [1-13C]pyruvate MRI and by DCE imaging. RESULTS: Rats receiving sevoflurane or FFM had blood glucose levels that were 1.3-fold to 1.4-fold higher than...... rats receiving inactin. A 2.9-fold and 4.8-fold increased13C-lactate/13C-pyruvate ratio was found in the FFM mixture anesthetized group compared with the sevoflurane and the inactin anesthetized groups. The FFM anesthesia resulted in a 50% lower renal plasma flow compared with the sevoflurane...

  6. Pulmonary alveolar microlithiasis. A review including ultrastructural and pulmonary function studies

    Prakash, U.B.; Barham, S.S.; Rosenow, E.C.; Brown, M.L.; Payne, W.S.

    1983-01-01

    Pulmonary alveolar microlithiasis is a rare disease of unknown cause in which calcium phosphate microliths are deposited throughout the lungs. These deposits are of sufficient density to be almost diagnostic on chest roentgenograms. The Mayo Clinic experience with 8 patients is added to the approximately 120 cases reported in the world literature. The age range of all patients is from newborn to 80 years, with a mean age at diagnosis of about 35 years. No sexual predominance has been noted, but in about half of the reported cases a familial pattern has been found. The progression of the disease is generally very slow, some patients having been followed up for more than 30 years without evidence of change. No specific treatment is available. Pulmonary function studies demonstrate a tendency toward a restrictive pattern. Technetium-99m scanning and scanning and transmission electron microscopy are useful procedures for analysis of pulmonary alveolar microliths

  7. A tryptophan derivative, ITE, enhances liver cell metabolic functions in vitro.

    Zhang, Xiaoqian; Lu, Juan; He, Bin; Tang, Lingling; Liu, Xiaoli; Zhu, Danhua; Cao, Hongcui; Wang, Yingjie; Li, Lanjuan

    2017-01-01

    Cell encapsulation provides a three-dimensional support by incorporating isolated cells into microcapsules with the goal of simultaneously maintaining cell survival and function, as well as providing active transport for a bioreactor in vitro similarly to that observed in vivo. However, the biotra-nsformation and metabolic functions of the encapsulated cells are not satisfactory for clinical applications. For this purpose, in this study, hepatoma-derived Huh7 cells/C3A cells were treated with 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), an endogenous non-toxic ligand for aryl hydrocarbon receptor, in monolayer cultures and on microspheres. The mRNA and protein levels, as well as the metabolic activities of drug metabolizing enzymes, albumin secretion and urea synthesis were determined. When the Huh7 and C3A cells cultured in a monolayer on two‑dimensional surfaces, ITE enhanced the protein levels and the metabolic activities of the major cytochrome P450 (CYP450) enzymes, CYP1A1, CYP1A2, CYP3A4 and CYP1B1, and slightly increased albumin secretion and urea synthesis. Moreover, when cultured on microspheres, ITE also substantially increased the protein levels and metabolic activities of CYP1A1, CYP1A2, CYP3A4 and CYP1B1 in both liver cell lines. On the whole, our findings indicate that ITE enhances the enzymatic activities of major CYP450 enzymes and the metabolic functions of liver cells cultured in monolayer or on microspheres, indicating that it may be utilized to improve the functions of hepatocytes. Thus, it may be used in the future for the treatment of liver diseases.

  8. A tryptophan derivative, ITE, enhances liver cell metabolic functions in vitro

    Zhang, Xiaoqian; Lu, Juan; He, Bin; Tang, Lingling; Liu, Xiaoli; Zhu, Danhua; Cao, Hongcui; Wang, Yingjie; Li, Lanjuan

    2017-01-01

    Cell encapsulation provides a three-dimensional support by incorporating isolated cells into microcapsules with the goal of simultaneously maintaining cell survival and function, as well as providing active transport for a bioreactor in vitro similarly to that observed in vivo. However, the biotransformation and metabolic functions of the encapsulated cells are not satisfactory for clinical applications. For this purpose, in this study, hepatoma-derived Huh7 cells/C3A cells were treated with 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), an endogenous non-toxic ligand for aryl hydrocarbon receptor, in monolayer cultures and on microspheres. The mRNA and protein levels, as well as the metabolic activities of drug metabolizing enzymes, albumin secretion and urea synthesis were determined. When the Huh7 and C3A cells cultured in a monolayer on two-dimensional surfaces, ITE enhanced the protein levels and the metabolic activities of the major cytochrome P450 (CYP450) enzymes, CYP1A1, CYP1A2, CYP3A4 and CYP1B1, and slightly increased albumin secretion and urea synthesis. Moreover, when cultured on microspheres, ITE also substantially increased the protein levels and metabolic activities of CYP1A1, CYP1A2, CYP3A4 and CYP1B1 in both liver cell lines. On the whole, our findings indicate that ITE enhances the enzymatic activities of major CYP450 enzymes and the metabolic functions of liver cells cultured in monolayer or on microspheres, indicating that it may be utilized to improve the functions of hepatocytes. Thus, it may be used in the future for the treatment of liver diseases. PMID:27959388

  9. Rb and p53 Liver Functions Are Essential for Xenobiotic Metabolism and Tumor Suppression.

    Sathidpak Nantasanti

    Full Text Available The tumor suppressors Retinoblastoma (Rb and p53 are frequently inactivated in liver diseases, such as hepatocellular carcinomas (HCC or infections with Hepatitis B or C viruses. Here, we discovered a novel role for Rb and p53 in xenobiotic metabolism, which represent a key function of the liver for metabolizing therapeutic drugs or toxins. We demonstrate that Rb and p53 cooperate to metabolize the xenobiotic 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC. DDC is metabolized mainly by cytochrome P450 (Cyp3a enzymes resulting in inhibition of heme synthesis and accumulation of protoporphyrin, an intermediate of heme pathway. Protoporphyrin accumulation causes bile injury and ductular reaction. We show that loss of Rb and p53 resulted in reduced Cyp3a expression decreased accumulation of protoporphyrin and consequently less ductular reaction in livers of mice fed with DDC for 3 weeks. These findings provide strong evidence that synergistic functions of Rb and p53 are essential for metabolism of DDC. Because Rb and p53 functions are frequently disabled in liver diseases, our results suggest that liver patients might have altered ability to remove toxins or properly metabolize therapeutic drugs. Strikingly the reduced biliary injury towards the oxidative stress inducer DCC was accompanied by enhanced hepatocellular injury and formation of HCCs in Rb and p53 deficient livers. The increase in hepatocellular injury might be related to reduce protoporphyrin accumulation, because protoporphrin is well known for its anti-oxidative activity. Furthermore our results indicate that Rb and p53 not only function as tumor suppressors in response to carcinogenic injury, but also in response to non-carcinogenic injury such as DDC.

  10. Exploiting immune cell metabolic machinery for functional HIV cure and the prevention of inflammaging [version 1; referees: 4 approved

    Clovis S. Palmer; Riya Palchaudhuri; Hassan Albargy; Mohamed Abdel-Mohsen; Suzanne M. Crowe

    2018-01-01

    An emerging paradigm in immunology suggests that metabolic reprogramming and immune cell activation and functions are intricately linked. Viral infections, such as HIV infection, as well as cancer force immune cells to undergo major metabolic challenges. Cells must divert energy resources in order to mount an effective immune response. However, the fact that immune cells adopt specific metabolic programs to provide host defense against intracellular pathogens and how this metabolic shift impa...

  11. Metabolic engineering pathways for rare sugars biosynthesis, physiological functionalities, and applications-a review.

    Bilal, Muhammad; Iqbal, Hafiz M N; Hu, Hongbo; Wang, Wei; Zhang, Xuehong

    2017-06-29

    Biomolecules like rare sugars and their derivatives are referred to as monosaccharides particularly uncommon in nature. Remarkably, many of them have various known physiological functions and biotechnological applications in cosmetics, nutrition, and pharmaceutical industries. Also, they can be exploited as starting materials for synthesizing fascinating natural bioproducts with significant biological activities. Regrettably, most of the rare sugars are quite expensive, and their synthetic chemical routes are both limited and economically unfeasible due to expensive raw materials. On the other hand, their production by enzymatic means often suffers from low space-time yields and high catalyst costs due to hasty enzyme denaturation/degradation. In this context, biosynthesis of rare sugars with industrial importance is receiving renowned scientific attention, across the globe. Moreover, the utilization of renewable resources as energy sources via microbial fermentation or microbial metabolic engineering has appeared a new tool. This article presents a comprehensive review of physiological functions and biotechnological applications of rare ketohexoses and aldohexoses, including D-psicose, D-tagatose, L-tagatose, D-sorbose, L-fructose, D-allose, L-glucose, D-gulose, L-talose, L-galactose, and L-fucose. Novel in-vivo recombination pathways based on aldolase and phosphatase for the biosynthesis of rare sugars, particularly D-psicose and D-sorbose using robust microbial strains are also deliberated.

  12. Hydrodynamics-based functional forms of activity metabolism: a case for the power-law polynomial function in animal swimming energetics.

    Papadopoulos, Anthony

    2009-01-01

    The first-degree power-law polynomial function is frequently used to describe activity metabolism for steady swimming animals. This function has been used in hydrodynamics-based metabolic studies to evaluate important parameters of energetic costs, such as the standard metabolic rate and the drag power indices. In theory, however, the power-law polynomial function of any degree greater than one can be used to describe activity metabolism for steady swimming animals. In fact, activity metabolism has been described by the conventional exponential function and the cubic polynomial function, although only the power-law polynomial function models drag power since it conforms to hydrodynamic laws. Consequently, the first-degree power-law polynomial function yields incorrect parameter values of energetic costs if activity metabolism is governed by the power-law polynomial function of any degree greater than one. This issue is important in bioenergetics because correct comparisons of energetic costs among different steady swimming animals cannot be made unless the degree of the power-law polynomial function derives from activity metabolism. In other words, a hydrodynamics-based functional form of activity metabolism is a power-law polynomial function of any degree greater than or equal to one. Therefore, the degree of the power-law polynomial function should be treated as a parameter, not as a constant. This new treatment not only conforms to hydrodynamic laws, but also ensures correct comparisons of energetic costs among different steady swimming animals. Furthermore, the exponential power-law function, which is a new hydrodynamics-based functional form of activity metabolism, is a special case of the power-law polynomial function. Hence, the link between the hydrodynamics of steady swimming and the exponential-based metabolic model is defined.

  13. Hydrodynamics-based functional forms of activity metabolism: a case for the power-law polynomial function in animal swimming energetics.

    Anthony Papadopoulos

    Full Text Available The first-degree power-law polynomial function is frequently used to describe activity metabolism for steady swimming animals. This function has been used in hydrodynamics-based metabolic studies to evaluate important parameters of energetic costs, such as the standard metabolic rate and the drag power indices. In theory, however, the power-law polynomial function of any degree greater than one can be used to describe activity metabolism for steady swimming animals. In fact, activity metabolism has been described by the conventional exponential function and the cubic polynomial function, although only the power-law polynomial function models drag power since it conforms to hydrodynamic laws. Consequently, the first-degree power-law polynomial function yields incorrect parameter values of energetic costs if activity metabolism is governed by the power-law polynomial function of any degree greater than one. This issue is important in bioenergetics because correct comparisons of energetic costs among different steady swimming animals cannot be made unless the degree of the power-law polynomial function derives from activity metabolism. In other words, a hydrodynamics-based functional form of activity metabolism is a power-law polynomial function of any degree greater than or equal to one. Therefore, the degree of the power-law polynomial function should be treated as a parameter, not as a constant. This new treatment not only conforms to hydrodynamic laws, but also ensures correct comparisons of energetic costs among different steady swimming animals. Furthermore, the exponential power-law function, which is a new hydrodynamics-based functional form of activity metabolism, is a special case of the power-law polynomial function. Hence, the link between the hydrodynamics of steady swimming and the exponential-based metabolic model is defined.

  14. Rb and p53 Liver Functions Are Essential for Xenobiotic Metabolism and Tumor Suppression

    Nantasanti, Sathidpak; Toussaint, Mathilda J. M.; Youssef, Sameh A.; Tooten, Peter C. J.; de Bruin, Alain

    2016-01-01

    The tumor suppressors Retinoblastoma (Rb) and p53 are frequently inactivated in liver diseases, such as hepatocellular carcinomas (HCC) or infections with Hepatitis B or C viruses. Here, we discovered a novel role for Rb and p53 in xenobiotic metabolism, which represent a key function of the liver

  15. Inflation including collapse of the wave function: the quasi-de Sitter case

    Leon, Gabriel [Universidad de Buenos Aires, Ciudad Universitaria-PabI, Departamento de Fisica, Facultad de Ciencias Exactas y Naturales, Buenos Aires (Argentina); Landau, Susana J. [Universidad de Buenos Aires y IFIBA, CONICET, Ciudad Universitaria-PabI, Departamento de Fisica, Facultad de Ciencias Exactas y Naturales, Buenos Aires (Argentina); Piccirilli, Maria Pia [Universidad Nacional de La Plata, Grupo de Astrofisica, Relatividad y Cosmologia, Facultad de Ciencias Astronomicas y Geofisicas, Pcia de Buenos Aires (Argentina)

    2015-08-15

    The precise physical mechanism describing the emergence of the seeds of cosmic structure from a perfect isotropic and homogeneous universe has not been fully explained by the standard version of inflationary models. To handle this shortcoming, D. Sudarsky and collaborators have developed a proposal: the self-induced collapse hypothesis. In this scheme, the objective collapse of the inflaton wave function is responsible for the emergence of inhomogeneity and anisotropy at all scales. In previous papers, the proposal was developed with an almost exact de Sitter space-time approximation for the background that led to a perfect scale-invariant power spectrum. In the present article, we consider a full quasi-de Sitter expansion and calculate the primordial power spectrum for three different choices of the self-induced collapse. The consideration of a quasi-de Sitter background allows us to distinguish departures from an exact scale-invariant power spectrum that are due to the inclusion of the collapse hypothesis. These deviations are also different from the prediction of standard inflationary models with a running spectral index. A comparison with the primordial power spectrum and the CMB temperature fluctuation spectrum preferred by the latest observational data is also discussed. From the analysis performed in this work, it follows that most of the collapse schemes analyzed in this paper are viable candidates to explain the present observations of the CMB fluctuation spectrum. (orig.)

  16. Inflation including collapse of the wave function: the quasi-de Sitter case

    Leon, Gabriel; Landau, Susana J.; Piccirilli, Maria Pia

    2015-01-01

    The precise physical mechanism describing the emergence of the seeds of cosmic structure from a perfect isotropic and homogeneous universe has not been fully explained by the standard version of inflationary models. To handle this shortcoming, D. Sudarsky and collaborators have developed a proposal: the self-induced collapse hypothesis. In this scheme, the objective collapse of the inflaton wave function is responsible for the emergence of inhomogeneity and anisotropy at all scales. In previous papers, the proposal was developed with an almost exact de Sitter space-time approximation for the background that led to a perfect scale-invariant power spectrum. In the present article, we consider a full quasi-de Sitter expansion and calculate the primordial power spectrum for three different choices of the self-induced collapse. The consideration of a quasi-de Sitter background allows us to distinguish departures from an exact scale-invariant power spectrum that are due to the inclusion of the collapse hypothesis. These deviations are also different from the prediction of standard inflationary models with a running spectral index. A comparison with the primordial power spectrum and the CMB temperature fluctuation spectrum preferred by the latest observational data is also discussed. From the analysis performed in this work, it follows that most of the collapse schemes analyzed in this paper are viable candidates to explain the present observations of the CMB fluctuation spectrum. (orig.)

  17. Proteomic analysis uncovers a metabolic phenotype in C. elegans after nhr-40 reduction of function

    Pohludka, Michal; Simeckova, Katerina; Vohanka, Jaroslav; Yilma, Petr; Novak, Petr; Krause, Michael W.; Kostrouchova, Marta; Kostrouch, Zdenek

    2008-01-01

    Caenorhabditis elegans has an unexpectedly large number (284) of genes encoding nuclear hormone receptors, most of which are nematode-specific and are of unknown function. We have exploited comparative two-dimensional chromatography of synchronized cultures of wild type C. elegans larvae and a mutant in nhr-40 to determine if proteomic approaches will provide additional insight into gene function. Chromatofocusing, followed by reversed-phase chromatography and mass spectrometry, identified altered chromatographic patterns for a set of proteins, many of which function in muscle and metabolism. Prompted by the proteomic analysis, we find that the penetrance of the developmental phenotypes in the mutant is enhanced at low temperatures and by food restriction. The combination of our phenotypic and proteomic analysis strongly suggests that NHR-40 provides a link between metabolism and muscle development. Our results highlight the utility of comparative two-dimensional chromatography to provide a relatively rapid method to gain insight into gene function

  18. Exploiting immune cell metabolic machinery for functional HIV cure and the prevention of inflammaging.

    Palmer, Clovis S; Palchaudhuri, Riya; Albargy, Hassan; Abdel-Mohsen, Mohamed; Crowe, Suzanne M

    2018-01-01

    An emerging paradigm in immunology suggests that metabolic reprogramming and immune cell activation and functions are intricately linked. Viral infections, such as HIV infection, as well as cancer force immune cells to undergo major metabolic challenges. Cells must divert energy resources in order to mount an effective immune response. However, the fact that immune cells adopt specific metabolic programs to provide host defense against intracellular pathogens and how this metabolic shift impacts immune cell functions and the natural course of diseases have only recently been appreciated. A clearer insight into how these processes are inter-related will affect our understanding of several fundamental aspects of HIV persistence. Even in patients with long-term use of anti-retroviral therapies, HIV infection persists and continues to cause chronic immune activation and inflammation, ongoing and cumulative damage to multiple organs systems, and a reduction in life expectancy. HIV-associated fundamental changes to the metabolic machinery of the immune system can promote a state of "inflammaging", a chronic, low-grade inflammation with specific immune changes that characterize aging, and can also contribute to the persistence of HIV in its reservoirs. In this commentary, we will bring into focus evolving concepts on how HIV modulates the metabolic machinery of immune cells in order to persist in reservoirs and how metabolic reprogramming facilitates a chronic state of inflammation that underlies the development of age-related comorbidities. We will discuss how immunometabolism is facilitating the changing paradigms in HIV cure research and outline the novel therapeutic opportunities for preventing inflammaging and premature development of age-related conditions in HIV + individuals.

  19. Structural and functional effects of heavy metals on the nervous system, including sense organs, of fish

    Baatrup, E

    1991-01-01

    metals are well known pollutants in the aquatic environment. Their interaction with relevant chemical stimuli may interfere with the communication between fish and environment. 5. The affinity for a number of ligands and macromolecules makes heavy metals most potent neurotoxins. 6. The present Mini......1. Today, fish in the environment are inevitably exposed to chemical pollution. Although most hazardous substances are present at concentrations far below the lethal level, they may still cause serious damage to the life processes of these animals. 2. Fish depend on an intact nervous system......, including their sense organs, for mediating relevant behaviour such as food search, predator recognition, communication and orientation. 3. Unfortunately, the nervous system is most vulnerable and injuries to its elements may dramatically change the behaviour and consequently the survival of fish. 4. Heavy...

  20. The FTD-like syndrome causing TREM2 T66M mutation impairs microglia function, brain perfusion, and glucose metabolism.

    Kleinberger, Gernot; Brendel, Matthias; Mracsko, Eva; Wefers, Benedikt; Groeneweg, Linda; Xiang, Xianyuan; Focke, Carola; Deußing, Maximilian; Suárez-Calvet, Marc; Mazaheri, Fargol; Parhizkar, Samira; Pettkus, Nadine; Wurst, Wolfgang; Feederle, Regina; Bartenstein, Peter; Mueggler, Thomas; Arzberger, Thomas; Knuesel, Irene; Rominger, Axel; Haass, Christian

    2017-07-03

    Genetic variants in the triggering receptor expressed on myeloid cells 2 (TREM2) increase the risk for several neurodegenerative diseases including Alzheimer's disease and frontotemporal dementia (FTD). Homozygous TREM2 missense mutations, such as p.T66M, lead to the FTD-like syndrome, but how they cause pathology is unknown. Using CRISPR/Cas9 genome editing, we generated a knock-in mouse model for the disease-associated Trem2 p.T66M mutation. Consistent with a loss-of-function mutation, we observe an intracellular accumulation of immature mutant Trem2 and reduced generation of soluble Trem2 similar to patients with the homozygous p.T66M mutation. Trem2 p.T66M knock-in mice show delayed resolution of inflammation upon in vivo lipopolysaccharide stimulation and cultured macrophages display significantly reduced phagocytic activity. Immunohistochemistry together with in vivo TSPO small animal positron emission tomography (μPET) demonstrates an age-dependent reduction in microglial activity. Surprisingly, perfusion magnetic resonance imaging and FDG-μPET imaging reveal a significant reduction in cerebral blood flow and brain glucose metabolism. Thus, we demonstrate that a TREM2 loss-of-function mutation causes brain-wide metabolic alterations pointing toward a possible function of microglia in regulating brain glucose metabolism. © 2017 The Authors.

  1. Transcriptional Regulation of T-Cell Lipid Metabolism: Implications for Plasma Membrane Lipid Rafts and T-Cell Function

    George A. Robinson

    2017-11-01

    Full Text Available It is well established that cholesterol and glycosphingolipids are enriched in the plasma membrane (PM and form signaling platforms called lipid rafts, essential for T-cell activation and function. Moreover, changes in PM lipid composition affect the biophysical properties of lipid rafts and have a role in defining functional T-cell phenotypes. Here, we review the role of transcriptional regulators of lipid metabolism including liver X receptors α/β, peroxisome proliferator-activated receptor γ, estrogen receptors α/β (ERα/β, and sterol regulatory element-binding proteins in T-cells. These receptors lie at the interface between lipid metabolism and immune cell function and are endogenously activated by lipids and/or hormones. Importantly, they regulate cellular cholesterol, fatty acid, glycosphingolipid, and phospholipid levels but are also known to modulate a broad spectrum of immune responses. The current evidence supporting a role for lipid metabolism pathways in controlling immune cell activation by influencing PM lipid raft composition in health and disease, and the potential for targeting lipid biosynthesis pathways to control unwanted T-cell activation in autoimmunity is reviewed.

  2. Mechanistic links between gut microbial community dynamics, microbial functions and metabolic health

    Ha, Connie WY; Lam, Yan Y; Holmes, Andrew J

    2014-01-01

    Gut microbes comprise a high density, biologically active community that lies at the interface of an animal with its nutritional environment. Consequently their activity profoundly influences many aspects of the physiology and metabolism of the host animal. A range of microbial structural components and metabolites directly interact with host intestinal cells and tissues to influence nutrient uptake and epithelial health. Endocrine, neuronal and lymphoid cells in the gut also integrate signals from these microbial factors to influence systemic responses. Dysregulation of these host-microbe interactions is now recognised as a major risk factor in the development of metabolic dysfunction. This is a two-way process and understanding the factors that tip host-microbiome homeostasis over to dysbiosis requires greater appreciation of the host feedbacks that contribute to regulation of microbial community composition. To date, numerous studies have employed taxonomic profiling approaches to explore the links between microbial composition and host outcomes (especially obesity and its comorbidities), but inconsistent host-microbe associations have been reported. Available data indicates multiple factors have contributed to discrepancies between studies. These include the high level of functional redundancy in host-microbiome interactions combined with individual variation in microbiome composition; differences in study design, diet composition and host system between studies; and inherent limitations to the resolution of rRNA-based community profiling. Accounting for these factors allows for recognition of the common microbial and host factors driving community composition and development of dysbiosis on high fat diets. New therapeutic intervention options are now emerging. PMID:25469018

  3. Plasminogen activator inhibitor-1 is elevated in patients with COPD independent of metabolic and cardiovascular function

    Waschki, Benjamin; Watz, Henrik; Holz, Olaf; Magnussen, Helgo; Olejnicka, Beata; Welte, Tobias; Rabe, Klaus F; Janciauskiene, Sabina

    2017-01-01

    Introduction Plasminogen activator inhibitor-1 (PAI-1), a major inhibitor of fibrinolysis, is associated with thrombosis, obesity, insulin resistance, dyslipidemia, and premature aging, which all are coexisting conditions of chronic obstructive pulmonary disease (COPD). The role of PAI-1 in COPD with respect to metabolic and cardiovascular functions is unclear. Methods In this study, which was nested within a prospective cohort study, the serum levels of PAI-1 were cross-sectionally measured in 74 stable COPD patients (Global Initiative for Chronic Obstructive Lung Disease [GOLD] Stages I–IV) and 18 controls without lung disease. In addition, triglycerides, high-density lipoprotein cholesterol, fasting plasma glucose, waist circumference, blood pressure, smoking status, high-sensitive C-reactive protein (hs-CRP), adiponectin, ankle–brachial index, N-terminal pro-B-type natriuretic peptide, and history of comorbidities were also determined. Results The serum levels of PAI-1 were significantly higher in COPD patients than in controls, independent of a broad spectrum of possible confounders including metabolic and cardiovascular dysfunction. A multivariate regression analysis revealed triglyceride and hs-CRP levels to be the best predictors of PAI-1 within COPD. GOLD Stages II and III remained independently associated with higher PAI-1 levels in a final regression analysis. Conclusion The data from the present study showed that the serum levels of PAI-1 are higher in patients with COPD and that moderate-to-severe airflow limitation, hypertriglyceridemia, and systemic inflammation are independent predictors of an elevated PAI-1 level. PAI-1 may be a potential biomarker candidate for COPD-specific and extra-pulmonary manifestations. PMID:28356730

  4. Recent insights into the implications of metabolism in plasmacytoid dendritic cell innate functions: Potential ways to control these functions [version 1; referees: 1 approved, 2 approved with reservations

    Philippe Saas

    2017-04-01

    Full Text Available There are more and more data concerning the role of cellular metabolism in innate immune cells, such as macrophages or conventional dendritic cells. However, few data are available currently concerning plasmacytoid dendritic cells (PDC, another type of innate immune cells. These cells are the main type I interferon (IFN producing cells, but they also secrete other pro-inflammatory cytokines (e.g., tumor necrosis factor or interleukin [IL]-6 or immunomodulatory factors (e.g., IL-10 or transforming growth factor-β. Through these functions, PDC participate in antimicrobial responses or maintenance of immune tolerance, and have been implicated in the pathophysiology of several autoimmune diseases. Recent data support the idea that the glycolytic pathway (or glycolysis, as well as lipid metabolism (including both cholesterol and fatty acid metabolism may impact some innate immune functions of PDC or may be involved in these functions after Toll-like receptor (TLR 7/9 triggering. Some differences may be related to the origin of PDC (human versus mouse PDC or blood-sorted versus FLT3 ligand stimulated-bone marrow-sorted PDC. The kinetics of glycolysis may differ between human and murine PDC. In mouse PDC, metabolism changes promoted by TLR7/9 activation may depend on an autocrine/paracrine loop, implicating type I IFN and its receptor IFNAR, explaining a delayed glycolysis. Moreover, PDC functions can be modulated by the metabolism of cholesterol and fatty acids. This may occur via the production of lipid ligands that activate nuclear receptors (e.g., liver X receptor [LXR] in PDC or through limiting intracellular cholesterol pool size (by statins or LXR agonists in these cells. Finally, lipid-activated nuclear receptors (i.e., LXR or peroxisome proliferator activated receptor may also directly interact with pro-inflammatory transcription factors, such as NF-κB. Here, we discuss how glycolysis and lipid metabolism may modulate PDC functions and how

  5. Metabolic mapping of functional activity in human subjects with the [18F]fluorodeoxyglucose technique

    Greenberg, J.H.; Reivich, M.; Alavi, A.

    1981-01-01

    The 2-[ 18 F]fluoro-2-deoxy-D-glucose technique was used to measure regional cerebral glucose utilization by human subjects during functional activation. Normal male volunteers subjected to one or more sensory stimuli exhibited focal increases in glucose metabolism in response to the stimulus. These results demonstrate that the technique is capable of providing functional maps in vivo related to both body region and submodality of sensory information in the human brain

  6. Morphological, functional and metabolic imaging biomarkers: assessment of vascular-disrupting effect on rodent liver tumours

    Wang, Huaijun; Li, Junjie; Keyzer, Frederik De; Yu, Jie; Feng, Yuanbo; Marchal, Guy; Ni, Yicheng; Chen, Feng; Nuyts, Johan

    2010-01-01

    To evaluate effects of a vascular-disrupting agent on rodent tumour models. Twenty rats with liver rhabdomyosarcomas received ZD6126 intravenously at 20 mg/kg, and 10 vehicle-treated rats were used as controls. Multiple sequences, including diffusion-weighted imaging (DWI) and dynamic contrast-enhanced MRI (DCE-MRI) with the microvascular permeability constant (K), were acquired at baseline, 1 h, 24 h and 48 h post-treatment by using 1.5-T MRI. [ 18 F]fluorodeoxyglucose micro-positron emission tomography ( 18 F-FDG μPET) was acquired pre- and post-treatment. The imaging biomarkers including tumour volume, enhancement ratio, necrosis ratio, apparent diffusion coefficient (ADC) and K from MRI, and maximal standardised uptake value (SUV max ) from FDG μPET were quantified and correlated with postmortem microangiography and histopathology. In the ZD6126-treated group, tumours grew slower with higher necrosis ratio at 48 h (P max dropped at 24 h (P < 0.01). Relative K of tumour versus liver at 48 h correlated with relative vascular density on microangiography (r = 0.93, P < 0.05). The imaging biomarkers allowed morphological, functional and metabolic quantifications of vascular shutdown, necrosis formation and tumour relapse shortly after treatment. A single dose of ZD6126 significantly diminished tumour blood supply and growth until 48 h post-treatment. (orig.)

  7. Features of Mineral Metabolism and Parathyroid Glands Functioning in Chronic Renal Disease

    L.P. Martynyuk

    2012-04-01

    Full Text Available The calcium phosphoric metabolism was analyzed depending on the severity of renal functioning disorders. Chronic renal disease is known to be associated with impaired mineral metabolism in terms of hypocalcaemia, hyperphosphatemia and enhanced level of Ca × P product that aggravates in chronic renal failure progression. The majority of patients with nephropathy have parathyroid hormone concentration to be different from target one recommended by NKF-K/DOQI (2003, at that secondary hyperparathyroidism prevails on pre-dialysis stage of chronic renal disease, the relative hypoparathyroidism is common among the patients received dialysis.

  8. Economic values of production and functional traits, including residual feed intake, in Finnish milk production.

    Hietala, P; Wolfová, M; Wolf, J; Kantanen, J; Juga, J

    2014-02-01

    Improving the feed efficiency of dairy cattle has a substantial effect on the economic efficiency and on the reduction of harmful environmental effects of dairy production through lower feeding costs and emissions from dairy farming. To assess the economic importance of feed efficiency in the breeding goal for dairy cattle, the economic values for the current breeding goal traits and the additional feed efficiency traits for Finnish Ayrshire cattle under production circumstances in 2011 were determined. The derivation of economic values was based on a bioeconomic model in which the profit of the production system was calculated, using the generated steady state herd structure. Considering beef production from dairy farms, 2 marketing strategies for surplus calves were investigated: (A) surplus calves were sold at a young age and (B) surplus calves were fattened on dairy farms. Both marketing strategies were unprofitable when subsidies were not included in the revenues. When subsidies were taken into account, a positive profitability was observed in both marketing strategies. The marginal economic values for residual feed intake (RFI) of breeding heifers and cows were -25.5 and -55.8 €/kg of dry matter per day per cow and year, respectively. The marginal economic value for RFI of animals in fattening was -29.5 €/kg of dry matter per day per cow and year. To compare the economic importance among traits, the standardized economic weight of each trait was calculated as the product of the marginal economic value and the genetic standard deviation; the standardized economic weight expressed as a percentage of the sum of all standardized economic weights was called relative economic weight. When not accounting for subsidies, the highest relative economic weight was found for 305-d milk yield (34% in strategy A and 29% in strategy B), which was followed by protein percentage (13% in strategy A and 11% in strategy B). The third most important traits were calving

  9. Deletion of GLUT1 and GLUT3 Reveals Multiple Roles for Glucose Metabolism in Platelet and Megakaryocyte Function

    Trevor P. Fidler

    2017-07-01

    Full Text Available Anucleate platelets circulate in the blood to facilitate thrombosis and diverse immune functions. Platelet activation leading to clot formation correlates with increased glycogenolysis, glucose uptake, glucose oxidation, and lactic acid production. Simultaneous deletion of glucose transporter (GLUT 1 and GLUT3 (double knockout [DKO] specifically in platelets completely abolished glucose uptake. In DKO platelets, mitochondrial oxidative metabolism of non-glycolytic substrates, such as glutamate, increased. Thrombosis and platelet activation were decreased through impairment at multiple activation nodes, including Ca2+ signaling, degranulation, and integrin activation. DKO mice developed thrombocytopenia, secondary to impaired pro-platelet formation from megakaryocytes, and increased platelet clearance resulting from cytosolic calcium overload and calpain activation. Systemic treatment with oligomycin, inhibiting mitochondrial metabolism, induced rapid clearance of platelets, with circulating counts dropping to zero in DKO mice, but not wild-type mice, demonstrating an essential role for energy metabolism in platelet viability. Thus, substrate metabolism is essential for platelet production, activation, and survival.

  10. Metatranscriptomic analysis of diverse microbial communities reveals core metabolic pathways and microbiome-specific functionality.

    Jiang, Yue; Xiong, Xuejian; Danska, Jayne; Parkinson, John

    2016-01-12

    Metatranscriptomics is emerging as a powerful technology for the functional characterization of complex microbial communities (microbiomes). Use of unbiased RNA-sequencing can reveal both the taxonomic composition and active biochemical functions of a complex microbial community. However, the lack of established reference genomes, computational tools and pipelines make analysis and interpretation of these datasets challenging. Systematic studies that compare data across microbiomes are needed to demonstrate the ability of such pipelines to deliver biologically meaningful insights on microbiome function. Here, we apply a standardized analytical pipeline to perform a comparative analysis of metatranscriptomic data from diverse microbial communities derived from mouse large intestine, cow rumen, kimchi culture, deep-sea thermal vent and permafrost. Sequence similarity searches allowed annotation of 19 to 76% of putative messenger RNA (mRNA) reads, with the highest frequency in the kimchi dataset due to its relatively low complexity and availability of closely related reference genomes. Metatranscriptomic datasets exhibited distinct taxonomic and functional signatures. From a metabolic perspective, we identified a common core of enzymes involved in amino acid, energy and nucleotide metabolism and also identified microbiome-specific pathways such as phosphonate metabolism (deep sea) and glycan degradation pathways (cow rumen). Integrating taxonomic and functional annotations within a novel visualization framework revealed the contribution of different taxa to metabolic pathways, allowing the identification of taxa that contribute unique functions. The application of a single, standard pipeline confirms that the rich taxonomic and functional diversity observed across microbiomes is not simply an artefact of different analysis pipelines but instead reflects distinct environmental influences. At the same time, our findings show how microbiome complexity and availability of

  11. Metabolomics analysis reveals the metabolic and functional roles of flavonoids in light-sensitive tea leaves.

    Zhang, Qunfeng; Liu, Meiya; Ruan, Jianyun

    2017-03-20

    As the predominant secondary metabolic pathway in tea plants, flavonoid biosynthesis increases with increasing temperature and illumination. However, the concentration of most flavonoids decreases greatly in light-sensitive tea leaves when they are exposed to light, which further improves tea quality. To reveal the metabolism and potential functions of flavonoids in tea leaves, a natural light-sensitive tea mutant (Huangjinya) cultivated under different light conditions was subjected to metabolomics analysis. The results showed that chlorotic tea leaves accumulated large amounts of flavonoids with ortho-dihydroxylated B-rings (e.g., catechin gallate, quercetin and its glycosides etc.), whereas total flavonoids (e.g., myricetrin glycoside, epigallocatechin gallate etc.) were considerably reduced, suggesting that the flavonoid components generated from different metabolic branches played different roles in tea leaves. Furthermore, the intracellular localization of flavonoids and the expression pattern of genes involved in secondary metabolic pathways indicate a potential photoprotective function of dihydroxylated flavonoids in light-sensitive tea leaves. Our results suggest that reactive oxygen species (ROS) scavenging and the antioxidation effects of flavonoids help chlorotic tea plants survive under high light stress, providing new evidence to clarify the functional roles of flavonoids, which accumulate to high levels in tea plants. Moreover, flavonoids with ortho-dihydroxylated B-rings played a greater role in photo-protection to improve the acclimatization of tea plants.

  12. The Changes of Energy Interactions between Nucleus Function and Mitochondria Functions Causing Transmutation of Chronic Inflammation into Cancer Metabolism.

    Ponizovskiy, Michail R

    2016-01-01

    Interactions between nucleus and mitochondria functions induce the mechanism of maintenance stability of cellular internal energy according to the first law of thermodynamics in able-bodied cells and changes the mechanisms of maintenance stability of cellular internal energy creating a transition stationary state of ablebodied cells into quasi-stationary pathologic states of acute inflammation transiting then into chronic inflammation and then transmuting into cancer metabolism. The mechanisms' influences of intruding etiologic pathologic agents (microbe, virus, etc.) lead to these changes of energy interactions between nucleus and mitochondria functions causing general acute inflammation, then passing into local chronic inflammation, and reversing into cancer metabolism transmutation. Interactions between biochemical processes and biophysical processes of cellular capacitors' operations create a supplementary mechanism of maintenance stability of cellular internal energy in the norm and in pathology. Discussion of some scientific works eliminates doubts of the authors of these works.

  13. Phospholipid metabolism and nuclear function: roles of the lipin family of phosphatidic acid phosphatases.

    Siniossoglou, Symeon

    2013-03-01

    Phospholipids play important roles in nuclear function as dynamic building blocks for the biogenesis of the nuclear membrane, as well as signals by which the nucleus communicates with other organelles, and regulate a variety of nuclear events. The mechanisms underlying the nuclear roles of phospholipids remain poorly understood. Lipins represent a family of phosphatidic acid (PA) phosphatases that are conserved from yeasts to humans and perform essential functions in lipid metabolism. Several studies have identified key roles for lipins and their regulators in nuclear envelope organization, gene expression and the maintenance of lipid homeostasis in yeast and metazoans. This review discusses recent advances in understanding the roles of lipins in nuclear structure and function. This article is part of a Special Issue entitled Phospholipids and Phospholipid Metabolism. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. 25 CFR 1000.361 - Will the annual review include a review of the Secretary's residual trust functions?

    2010-04-01

    ... Evaluations § 1000.361 Will the annual review include a review of the Secretary's residual trust functions... Department official will be notified of the need for corrective action. The review of the Secretary's trust... 25 Indians 2 2010-04-01 2010-04-01 false Will the annual review include a review of the Secretary...

  15. Regional myocardial blood flow, metabolism and function assessed noninvasively by positron emission tomography

    Schelbert, H.R.; Phelps, M.E.; Hoffman, E.; Huang, S.; Kuhl, D.E.

    1979-01-01

    Positron emission computed tomography is a new technique for the noninvasive measure of myocardial blood flow, mechanical function and, in particular, metabolism. The capability of this new study means is due to the technological innovations of the imaging device and the availability of radioactive tracers that are specific for blood flow and metabolism. The device permits recording of cross-sectional images of the left ventricular myocardium that reflect quantitatively regional tracer tissue concentrations. By employing tracer kinetic models this new technique permits the measurement of regional glucose and fatty acid metabolism of the heart. While already an important new tool for investigative studies into cardiac physiology and pathophysiology, the clinical utility of positron emission tomography remains to be defined.

  16. Regional myocardial blood flow, metabolism and function assessed noninvasively by positron emission tomography

    Schelbert, H.R.; Phelps, M.E.; Hoffman, E.; Huang, S.; Kuhl, D.E.

    1979-01-01

    Positron emission computed tomography is a new technique for the noninvasive measure of myocardial blood flow, mechanical function and, in particular, metabolism. The capability of this new study means is due to the technological innovations of the imaging device and the availability of radioactive tracers that are specific for blood flow and metabolism. The device permits recording of cross-sectional images of the left ventricular myocardium that reflect quantitatively regional tracer tissue concentrations. By employing tracer kinetic models this new technique permits the measurement of regional glucose and fatty acid metabolism of the heart. While already an important new tool for investigative studies into cardiac physiology and pathophysiology, the clinical utility of positron emission tomography remains to be defined

  17. Thyroid peroxidase antibodies in pregnant women with type 1 diabetes: impact on thyroid function, metabolic control and pregnancy outcome

    Vestgaard, Marianne; Nielsen, Lene Ringholm; Rasmussen, Åse Krogh

    2008-01-01

    In pregnant women with type 1 diabetes, we evaluated whether the presence of thyroid peroxidase autoantibodies (anti-TPO) was associated with changes in thyroid function, metabolic control and pregnancy outcome.......In pregnant women with type 1 diabetes, we evaluated whether the presence of thyroid peroxidase autoantibodies (anti-TPO) was associated with changes in thyroid function, metabolic control and pregnancy outcome....

  18. High-Mobility Group Box 1 Disrupts Metabolic Function with Cigarette Smoke Exposure in a Ceramide-Dependent Manner

    Oliver J. Taylor

    2017-05-01

    Full Text Available We have previously found that cigarette smoke disrupts metabolic function, in part, by increasing muscle ceramide accrual. To further our understanding of this, we sought to determine the role of the cytokine high-mobility group box 1 (HMGB1, which is increased with smoke exposure, in smoke-induced muscle metabolic perturbations. To test this theory, we determined HMGB1 from lungs of human smokers, as well as from lung cells from mice exposed to cigarette smoke. We also treated cells and mice directly with HMGB1, in the presence or absence of myriocin, an inhibitor of serine palmitoyltransferase, the rate-limiting enzyme in ceramide biosynthesis. Outcomes included assessments of insulin resistance and muscle mitochondrial function. HMGB1 was significantly increased in both human lungs and rodent alveolar macrophages. Further testing revealed that HMGB1 treatment elicited a widespread increase in ceramide species and reduction in myotube mitochondrial respiration, an increase in reactive oxygen species, and reduced insulin-stimulated Akt phosphorylation. Inhibition of ceramide biosynthesis with myriocin was protective. In mice, by comparing treatments of HMGB1 injections with or without myriocin, we found that HMGB1 injections resulted in increased muscle ceramides, especially C16 and C24, which were necessary for reduced muscle mitochondrial respiration and compromised insulin and glucose tolerance. In conclusion, HMGB1 may be a necessary intermediate in the ceramide-dependent metabolic consequences of cigarette smoke exposure.

  19. Maternal Concentrations of Perfluoroalkyl Substances and Fetal Markers of Metabolic Function and Birth Weight

    Ashley-Martin, Jillian; Dodds, Linda; Arbuckle, Tye E.; Bouchard, Maryse F.; Fisher, Mandy; Morriset, Anne-Sophie; Monnier, Patricia; Shapiro, Gabriel D.; Ettinger, Adrienne S.; Dallaire, Renee; Taback, Shayne; Fraser, William; Platt, Robert W.

    2017-01-01

    Abstract Perfluoroalkyl substances (PFAS) are ubiquitous, persistent chemicals that have been widely used in the production of common household and consumer goods for their nonflammable, lipophobic, and hydrophobic properties. Inverse associations between maternal or umbilical cord blood concentrations of perfluorooctanoic acid and perfluorooctanesulfonate and birth weight have been identified. This literature has primarily examined each PFAS individually without consideration of the potential influence of correlated exposures. Further, the association between PFAS exposures and indicators of metabolic function (i.e., leptin and adiponectin) has received limited attention. We examined associations between first-trimester maternal plasma PFAS concentrations and birth weight and cord blood concentrations of leptin and adiponectin using data on 1,705 mother-infant pairs from the Maternal Infant Research on Environmental Chemicals (MIREC) Study, a trans-Canada birth cohort study that recruited women between 2008 and 2011. Bayesian hierarchical models were used to quantify associations and calculate credible intervals. Maternal perfluorooctanoic acid concentrations were inversely associated with birth weight z score, though the null value was included in all credible intervals (log10 β = −0.10, 95% credible interval: −0.34, 0.13). All associations between maternal PFAS concentrations and cord blood adipocytokine concentrations were of small magnitude and centered around the null value. Follow-up in a cohort of children is required to determine how the observed associations manifest in childhood. PMID:28172036

  20. The SETD8/PR-Set7 Methyltransferase Functions as a Barrier to Prevent Senescence-Associated Metabolic Remodeling

    Hiroshi Tanaka

    2017-02-01

    Full Text Available Summary: Cellular senescence is an irreversible growth arrest that contributes to development, tumor suppression, and age-related conditions. Senescent cells show active metabolism compared with proliferating cells, but the underlying mechanisms remain unclear. Here we show that the SETD8/PR-Set7 methyltransferase, which catalyzes mono-methylation of histone H4 at lysine 20 (H4K20me1, suppresses nucleolar and mitochondrial activities to prevent cellular senescence. SETD8 protein was selectively downregulated in both oncogene-induced and replicative senescence. Inhibition of SETD8 alone was sufficient to trigger senescence. Under these states, the expression of genes encoding ribosomal proteins (RPs and ribosomal RNAs as well as the cyclin-dependent kinase (CDK inhibitor p16INK4A was increased, with a corresponding reduction of H4K20me1 at each locus. As a result, the loss of SETD8 concurrently stimulated nucleolar function and retinoblastoma protein-mediated mitochondrial metabolism. In conclusion, our data demonstrate that SETD8 acts as a barrier to prevent cellular senescence through chromatin-mediated regulation of senescence-associated metabolic remodeling. : Tanaka et al. show that SETD8/PR-Set7 methyltransferase represses senescence-associated genes including ribosomal proteins, ribosomal RNAs, and p16INK4A by catalyzing mono-methylation of histone H4 at lysine 20. Depletion of SETD8 derepresses these genes, resulting in nucleolar and mitochondrial coactivation characteristic of senescence-associated metabolic remodeling. Keywords: SETD8/PR-Set7, H4K20 methylation, senescence-associated metabolic remodeling, nucleolus, mitochondria

  1. Dynamics of Panax ginseng Rhizospheric Soil Microbial Community and Their Metabolic Function

    Yong Li

    2014-01-01

    Full Text Available The bacterial communities of 1- to 6-year ginseng rhizosphere soils were characterized by culture-independent approaches, random amplified polymorphic DNA (RAPD, and amplified ribosomal DNA restriction analysis (ARDRA. Culture-dependent method (Biolog was used to investigate the metabolic function variance of microbe living in rhizosphere soil. Results showed that significant genetic and metabolic function variance were detected among soils, and, with the increasing of cultivating years, genetic diversity of bacterial communities in ginseng rhizosphere soil tended to be decreased. Also we found that Verrucomicrobia, Acidobacteria, and Proteobacteria were the dominants in rhizosphere soils, but, with the increasing of cultivating years, plant disease prevention or plant growth promoting bacteria, such as Pseudomonas, Burkholderia, and Bacillus, tended to be rare.

  2. Functional proteomic analysis of corticosteroid pharmacodynamics in rat liver: Relationship to hepatic stress, signaling, energy regulation, and drug metabolism.

    Ayyar, Vivaswath S; Almon, Richard R; DuBois, Debra C; Sukumaran, Siddharth; Qu, Jun; Jusko, William J

    2017-05-08

    Corticosteroids (CS) are anti-inflammatory agents that cause extensive pharmacogenomic and proteomic changes in multiple tissues. An understanding of the proteome-wide effects of CS in liver and its relationships to altered hepatic and systemic physiology remains incomplete. Here, we report the application of a functional pharmacoproteomic approach to gain integrated insight into the complex nature of CS responses in liver in vivo. An in-depth functional analysis was performed using rich pharmacodynamic (temporal-based) proteomic data measured over 66h in rat liver following a single dose of methylprednisolone (MPL). Data mining identified 451 differentially regulated proteins. These proteins were analyzed on the basis of temporal regulation, cellular localization, and literature-mined functional information. Of the 451 proteins, 378 were clustered into six functional groups based on major clinically-relevant effects of CS in liver. MPL-responsive proteins were highly localized in the mitochondria (20%) and cytosol (24%). Interestingly, several proteins were related to hepatic stress and signaling processes, which appear to be involved in secondary signaling cascades and in protecting the liver from CS-induced oxidative damage. Consistent with known adverse metabolic effects of CS, several rate-controlling enzymes involved in amino acid metabolism, gluconeogenesis, and fatty-acid metabolism were altered by MPL. In addition, proteins involved in the metabolism of endogenous compounds, xenobiotics, and therapeutic drugs including cytochrome P450 and Phase-II enzymes were differentially regulated. Proteins related to the inflammatory acute-phase response were up-regulated in response to MPL. Functionally-similar proteins showed large diversity in their temporal profiles, indicating complex mechanisms of regulation by CS. Clinical use of corticosteroid (CS) therapy is frequent and chronic. However, current knowledge on the proteome-level effects of CS in liver and

  3. Regulation and function of versatile aerobic and anaerobic respiratory metabolism in Pseudomonas aeruginosa

    Hiroyuki eArai

    2011-05-01

    Full Text Available Pseudomonas aeruginosa is a ubiquitously distributed opportunistic pathogen that inhabits soil and water as well as animal-, human-, and plant-host-associated environments. The ubiquity would be attributed to its very versatile energy metabolism. P. aeruginosa has a highly branched respiratory chain terminated by multiple terminal oxidases and denitrification enzymes. Five terminal oxidases for aerobic respiration have been identified in the P. aeruginosa cells. Three of them, the cbb3-1 oxidase, the cbb3-2 oxidase, and the aa3 oxidase, are cytochrome c oxidases and the other two, the bo3 oxidase and the cyanide-insensitive oxidase, are quinol oxidases. Each oxidase has a specific affinity for oxygen, efficiency of energy coupling, and tolerance to various stresses such as cyanide and reactive nitrogen species. These terminal oxidases are used differentially according to the environmental conditions. P. aeruginosa also has a complete set of the denitrification enzymes that reduce nitrate to molecular nitrogen via nitrite, nitric oxide (NO, and nitrous oxide. These nitrogen oxides function as alternative electron acceptors and enable P. aeruginosa to grow under anaerobic conditions. One of the denitrification enzymes, NO reductase, is also expected to function for detoxification of NO produced by the host immune defense system. The control of the expression of these aerobic and anaerobic respiratory enzymes would contribute to the adaptation of P. aeruginosa to a wide range of environmental conditions including in the infected hosts. Characteristics of these respiratory enzymes and the regulatory system that controls the expression of the respiratory genes in the P. aeruginosa cells are overviewed in this article.

  4. A predator-prey model with a holling type I functional response including a predator mutual interference

    Seo, G.; DeAngelis, D.L.

    2011-01-01

    The most widely used functional response in describing predator-prey relationships is the Holling type II functional response, where per capita predation is a smooth, increasing, and saturating function of prey density. Beddington and DeAngelis modified the Holling type II response to include interference of predators that increases with predator density. Here we introduce a predator-interference term into a Holling type I functional response. We explain the ecological rationale for the response and note that the phase plane configuration of the predator and prey isoclines differs greatly from that of the Beddington-DeAngelis response; for example, in having three possible interior equilibria rather than one. In fact, this new functional response seems to be quite unique. We used analytical and numerical methods to show that the resulting system shows a much richer dynamical behavior than the Beddington-DeAngelis response, or other typically used functional responses. For example, cyclic-fold, saddle-fold, homoclinic saddle connection, and multiple crossing bifurcations can all occur. We then use a smooth approximation to the Holling type I functional response with predator mutual interference to show that these dynamical properties do not result from the lack of smoothness, but rather from subtle differences in the functional responses. ?? 2011 Springer Science+Business Media, LLC.

  5. Functional analysis of free fatty acid receptor GPR120 in human eosinophils: implications in metabolic homeostasis.

    Konno, Yasunori; Ueki, Shigeharu; Takeda, Masahide; Kobayashi, Yoshiki; Tamaki, Mami; Moritoki, Yuki; Oyamada, Hajime; Itoga, Masamichi; Kayaba, Hiroyuki; Omokawa, Ayumi; Hirokawa, Makoto

    2015-01-01

    Recent evidence has shown that eosinophils play an important role in metabolic homeostasis through Th2 cytokine production. GPR120 (FFA4) is a G protein-coupled receptor (GPCR) for long-chain fatty acids that functions as a regulator of physiological energy metabolism. In the present study, we aimed to investigate whether human eosinophils express GPR120 and, if present, whether it possesses a functional capacity on eosinophils. Eosinophils isolated from peripheral venous blood expressed GPR120 at both the mRNA and protein levels. Stimulation with a synthetic GPR120 agonist, GW9508, induced rapid down-regulation of cell surface expression of GPR120, suggesting ligand-dependent receptor internalization. Although GPR120 activation did not induce eosinophil chemotactic response and degranulation, we found that GW9508 inhibited eosinophil spontaneous apoptosis and Fas receptor expression. The anti-apoptotic effect was attenuated by phosphoinositide 3-kinase (PI3K) inhibitors and was associated with inhibition of caspase-3 activity. Eosinophil response investigated using ELISpot assay indicated that stimulation with a GPR120 agonist induced IL-4 secretion. These findings demonstrate the novel functional properties of fatty acid sensor GPR120 on human eosinophils and indicate the previously unrecognized link between nutrient metabolism and the immune system.

  6. Air Pollution Exposure During Pregnancy and Fetal Markers of Metabolic function

    Lavigne, Eric; Ashley-Martin, Jillian; Dodds, Linda; Arbuckle, Tye E.; Hystad, Perry; Johnson, Markey; Crouse, Dan L.; Ettinger, Adrienne S.; Shapiro, Gabriel D.; Fisher, Mandy; Morisset, Anne-Sophie; Taback, Shayne; Bouchard, Maryse F.; Sun, Liu; Monnier, Patricia; Dallaire, Renée; Fraser, William D.

    2016-01-01

    Previous evidence suggests that exposure to outdoor air pollution during pregnancy could alter fetal metabolic function, which could increase the risk of obesity in childhood. However, to our knowledge, no epidemiologic study has investigated the association between prenatal exposure to air pollution and indicators of fetal metabolic function. We investigated the association between maternal exposure to nitrogen dioxide and fine particulate matter (aerodynamic diameter ≤2.5 µm) and umbilical cord blood leptin and adiponectin levels with mixed-effects linear regression models among 1,257 mother-infant pairs from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, conducted in Canada (2008–2011). We observed that an interquartile-range increase in average exposure to fine particulate matter (3.2 µg/m3) during pregnancy was associated with an 11% (95% confidence interval: 4, 17) increase in adiponectin levels. We also observed 13% (95% confidence interval: 6, 20) higher adiponectin levels per interquartile-range increase in average exposure to nitrogen dioxide (13.6 parts per billion) during pregnancy. Significant associations were seen between air pollution markers and cord blood leptin levels in models that adjusted for birth weight z score but not in models that did not adjust for birth weight z score. The roles of prenatal exposure to air pollution and fetal metabolic function in the potential development of childhood obesity should be further explored. PMID:27026336

  7. Cerebral energy metabolism and the brain's functional network architecture: an integrative review.

    Lord, Louis-David; Expert, Paul; Huckins, Jeremy F; Turkheimer, Federico E

    2013-09-01

    Recent functional magnetic resonance imaging (fMRI) studies have emphasized the contributions of synchronized activity in distributed brain networks to cognitive processes in both health and disease. The brain's 'functional connectivity' is typically estimated from correlations in the activity time series of anatomically remote areas, and postulated to reflect information flow between neuronal populations. Although the topological properties of functional brain networks have been studied extensively, considerably less is known regarding the neurophysiological and biochemical factors underlying the temporal coordination of large neuronal ensembles. In this review, we highlight the critical contributions of high-frequency electrical oscillations in the γ-band (30 to 100 Hz) to the emergence of functional brain networks. After describing the neurobiological substrates of γ-band dynamics, we specifically discuss the elevated energy requirements of high-frequency neural oscillations, which represent a mechanistic link between the functional connectivity of brain regions and their respective metabolic demands. Experimental evidence is presented for the high oxygen and glucose consumption, and strong mitochondrial performance required to support rhythmic cortical activity in the γ-band. Finally, the implications of mitochondrial impairments and deficits in glucose metabolism for cognition and behavior are discussed in the context of neuropsychiatric and neurodegenerative syndromes characterized by large-scale changes in the organization of functional brain networks.

  8. Fabp4-Cre-mediated Sirt6 deletion impairs adipose tissue function and metabolic homeostasis in mice.

    Xiong, Xiwen; Zhang, Cuicui; Zhang, Yang; Fan, Rui; Qian, Xinlai; Dong, X Charlie

    2017-06-01

    SIRT6 is a member of sirtuin family of deacetylases involved in diverse processes including genome stability, metabolic homeostasis and anti-inflammation. However, its function in the adipose tissue is not well understood. To examine the metabolic function of SIRT6 in the adipose tissue, we generated two mouse models that are deficient in Sirt6 using the Cre-lox approach. Two commonly used Cre lines that are driven by either the mouse Fabp4 or Adipoq gene promoter were chosen for this study. The Sirt6- knockout mice generated by the Fabp4-Cre line ( Sirt6 f/f : Fabp4-Cre) had a significant increase in both body weight and fat mass and exhibited glucose intolerance and insulin resistance as compared with the control wild-type mice. At the molecular levels, the Sirt6 f/f :Fabp4-Cre-knockout mice had increased expression of inflammatory genes including F4/80, TNFα, IL-6 and MCP-1 in both white and brown adipose tissues. Moreover, the knockout mice showed decreased expression of the adiponectin gene in the white adipose tissue and UCP1 in the brown adipose tissue, respectively. In contrast, the Sirt6 knockout mice generated by the Adipoq-Cre line ( Sirt6 f/f :Adipoq-Cre) only had modest insulin resistance. In conclusion, our data suggest that the function of SIRT6 in the Fabp4-Cre-expressing cells in addition to mature adipocytes plays a critical role in body weight maintenance and metabolic homeostasis. © 2017 Society for Endocrinology.

  9. Correlation between liver function tests and metabolic syndrome in hepatitis-free elderly

    Hung-Sheng Shang

    2015-01-01

    Full Text Available Background: We aimed to investigate the relationship between liver function tests (LFTs and metabolic syndrome (MetS as several studies have shown positive correlations between some of the LFTs, including alanine aminotransferase (ALT and γ-glutamyl transpeptidase (γ-GT, and MetS but have not fully explored the same in the elderly. Owing to the progress in public health, the aging of the general population becomes a major issue. Design: We enrolled subjects aged over 60 years who underwent routine health checkups in a Health Screening Center after excluding subjects with a history of hepatitis B or C infection, excessive alcohol consumption, liver fibrosis, cirrhosis, acute hepatitis, diabetes, hypertension, dyslipidemia, cardiovascular disease, or receiving medications for these diseases. Finally, 9,282 participants were eligible for analysis. Statistical Analysis: All data were tested for normal distribution with the Kolmogorov-Smirnov test and for homogeneity of variances with the Levene′s test. A t-test was used to evaluate the differences between the two groups. Univariate and multivariate regressions were used to observe correlations between different parameters. Receiver operating characteristic curves of each LFT were used to predict MetS. Areas under curves and 95% confidence interval were also estimated and compared. Results: With the exception of aspartate aminotransferase and α-fetal protein, the results of LFTs, including total and direct bilirubin, alkaline phosphatase (ALP, ALT, and γ-GT, were altered in the group with MetS. Furthermore, the levels of γ-GT in men and ALP in women were independently associated with all MetS components and had the highest areas under receiver operating characteristic curves. Conclusion: Abnormal LFTs are highly correlated with MetS in the hepatitis-free elderly, with levels of γ-GT in men and ALP in women being the most important factors. LFTs may represent an auxiliary tool for the

  10. Plasminogen activator inhibitor-1 is elevated in patients with COPD independent of metabolic and cardiovascular function

    Waschki B

    2017-03-01

    Full Text Available Benjamin Waschki,1–3 Henrik Watz,2,3 Olaf Holz,4,5 Helgo Magnussen,2,3 Beata Olejnicka,6 Tobias Welte,5,7 Klaus F Rabe,1,3 Sabina Janciauskiene5,7 1Pneumology, LungenClinic Grosshansdorf, Grosshansdorf, Germany; 2Pulmonary Research Institute at LungenClinic Grosshansdorf, Grosshansdorf, Germany; 3Airway Research Center North (ARCN, German Center for Lung Research (DZL, Grosshansdorf, Germany; 4Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany; 5Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH, German Center for Lung Research (DZL, Hannover, Germany; 6Department of Medicine, Trelleborg Hospital, Trelleborg, Sweden; 7Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany Introduction: Plasminogen activator inhibitor-1 (PAI-1, a major inhibitor of fibrinolysis, is associated with thrombosis, obesity, insulin resistance, dyslipidemia, and premature aging, which all are coexisting conditions of chronic obstructive pulmonary disease (COPD. The role of PAI-1 in COPD with respect to metabolic and cardiovascular functions is unclear. Methods: In this study, which was nested within a prospective cohort study, the serum levels of PAI-1 were cross-sectionally measured in 74 stable COPD patients (Global Initiative for Chronic Obstructive Lung Disease [GOLD] Stages I–IV and 18 controls without lung disease. In addition, triglycerides, high-density lipoprotein cholesterol, fasting plasma glucose, waist circumference, blood pressure, smoking status, high-sensitive C-reactive protein (hs-CRP, adiponectin, ankle–brachial index, N-terminal pro-B-type natriuretic peptide, and history of comorbidities were also determined. Results: The serum levels of PAI-1 were significantly higher in COPD patients than in controls, independent of a broad spectrum of possible confounders including metabolic and cardiovascular dysfunction. A multivariate regression analysis revealed

  11. The Role of Diacylglycerol Acyltransferase (DGAT) 1 and 2 in Cardiac Metabolism and Function.

    Roe, Nathan D; Handzlik, Michal K; Li, Tao; Tian, Rong

    2018-03-21

    It is increasingly recognized that synthesis and turnover of cardiac triglyceride (TG) play a pivotal role in the regulation of lipid metabolism and function of the heart. The last step in TG synthesis is catalyzed by diacylglycerol:acyltransferase (DGAT) which esterifies the diacylglycerol with a fatty acid. Mammalian heart has two DGAT isoforms, DGAT1 and DGAT2, yet their roles in cardiac metabolism and function remain poorly defined. Here, we show that inactivation of DGAT1 or DGAT2 in adult mouse heart results in a moderate suppression of TG synthesis and turnover. Partial inhibition of DGAT activity increases cardiac fatty acid oxidation without affecting PPARα signaling, myocardial energetics or contractile function. Moreover, coinhibition of DGAT1/2 in the heart abrogates TG turnover and protects the heart against high fat diet-induced lipid accumulation with no adverse effects on basal or dobutamine-stimulated cardiac function. Thus, the two DGAT isoforms in the heart have partially redundant function, and pharmacological inhibition of one DGAT isoform is well tolerated in adult hearts.

  12. Metabolic correlates of general cognitive function in nondemented elderly subjects: an FDG PET study

    Cho, Sang Soo; Kwak, Young Bin; Lee, Eun Ju; Ryu, Chang Hyung; Chey, Jean Yung; Kim, Sang Eun

    2004-01-01

    While many studies examined the neural correlates of individual cognitive functions, few made efforts to identify the neural networks associated with general cognitive function. General cognitive function decline in the elderly population is not infrequent. This study examined the brain areas associated with general cognitive function in the elderly subjects. Community-dwelling 116 elderly subjects without dementing illnesses (age, 71±5 y; 13 males and 103 females) participated. General cognitive ability was assessed with the Dementia Rating Scale (K-DRS), which is composed of five subtests of attention, initiation and perseveration, construction, conceptualization, and memory. The EVLT (Elderly Verbal Learning Test), a nine-word list learning test, was used for general memory assessment. Brain FDG PET scans were acquired in all subjects. Brain regions where metabolic levels are correlated with the total scores of K-DRS and EVLT were examined using SPM99. There was a significant positive correlation (P < 0.01 uncorrected, k=100) between the total score of K-DRS and glucose metabolism in the bilateral posterior cingulate gyri, bilateral inferior frontal gyri, left caudate, left inferior parietal lobule, right precuneus, bilateral unci, right parahippocampal gyrus, and right anterior cingulate gyrus. A significant positive correlation between the total score of EVLT and glucose metabolism was shown in the right precuneus, right posterior cingulate gyrus, left insula, bilateral inferior parietal lobules, left anterior cingulate gyrus, left caudate, right inferior frontal gyrus (P < 0.01 uncorrected, k=100). Our data showed the brain regions that are associated with general cognitive function in the elderly. Those regions may serve as the neural substrated of cognitive dysfunction associated with neurodegenerative and cerebrovascular diseases in elderly subjects

  13. Systemic down-regulation of delta-9 desaturase promotes muscle oxidative metabolism and accelerates muscle function recovery following nerve injury.

    Ghulam Hussain

    Full Text Available The progressive deterioration of the neuromuscular axis is typically observed in degenerative conditions of the lower motor neurons, such as amyotrophic lateral sclerosis (ALS. Neurodegeneration in this disease is associated with systemic metabolic perturbations, including hypermetabolism and dyslipidemia. Our previous gene profiling studies on ALS muscle revealed down-regulation of delta-9 desaturase, or SCD1, which is the rate-limiting enzyme in the synthesis of monounsaturated fatty acids. Interestingly, knocking out SCD1 gene is known to induce hypermetabolism and stimulate fatty acid beta-oxidation. Here we investigated whether SCD1 deficiency can affect muscle function and its restoration in response to injury. The genetic ablation of SCD1 was not detrimental per se to muscle function. On the contrary, muscles in SCD1 knockout mice shifted toward a more oxidative metabolism, and enhanced the expression of synaptic genes. Repressing SCD1 expression or reducing SCD-dependent enzymatic activity accelerated the recovery of muscle function after inducing sciatic nerve crush. Overall, these findings provide evidence for a new role of SCD1 in modulating the restorative potential of skeletal muscles.

  14. Mitochondrial pyruvate carrier function determines cell stemness and metabolic reprogramming in cancer cells

    Li, Xiaoran; Kan, Quancheng; Fan, Zhirui; Li, Yaqing; Ji, Yasai; Zhao, Jing; Zhang, Mingzhi; Grigalavicius, Mantas; Berge, Viktor; Goscinski, Mariusz Adam; M. Nesland, Jahn; Suo, Zhenhe

    2017-01-01

    One of the remarkable features of cancer cells is aerobic glycolysis, a phenomenon known as the “Warburg Effect”, in which cells rely preferentially on glycolysis instead of oxidative phosphorylation (OXPHOS) as the main energy source even in the presence of high oxygen tension. Cells with dysfunctional mitochondria are unable to generate sufficient ATP from mitochondrial OXPHOS, and then are forced to rely on glycolysis for ATP generation. Here we report our results in a prostate cancer cell line in which the mitochondrial pyruvate carrier 1 (MPC1) gene was knockout. It was discovered that the MPC1 gene knockout cells revealed a metabolism reprogramming to aerobic glycolysis with reduced ATP production, and the cells became more migratory and resistant to both chemotherapy and radiotherapy. In addition, the MPC1 knockout cells expressed significantly higher levels of the stemness markers Nanog, Hif1α, Notch1, CD44 and ALDH. To further verify the correlation of MPC gene function and cell stemness/metabolic reprogramming, MPC inhibitor UK5099 was applied in two ovarian cancer cell lines and similar results were obtained. Taken together, our results reveal that functional MPC may determine the fate of metabolic program and the stemness status of cancer cells in vitro. PMID:28624784

  15. Changes of thyroid function, autoantibodies, bone mineral density and bone metabolism indexes in patients with hyperthyroidism

    Yan Wang

    2016-07-01

    Full Text Available Objective: To investigate the changes of thyroid function, autoantibodies, bone mineral density and bone metabolism in patients with hyperthyroidism. Methods: A total of 216 cases of hyperthyroidism in our hospital from December 2015 to January 2015 were selected as the case group, 216 cases of healthy people selected the same period in our hospital physical examination center as the control group, detected thyroid function, autoantibodies, bone mineral density and bone metabolism indexes of all the studied subjects and compared with each other. Results: In this study, it was found that diastolic blood pressure, BMI, triglyceride, total cholesterol, HDL-C, VLDL-C, TSH were all significantly lower than the control group (P<0.05, systolic blood pressure, LDL-C, GLU, T3, T4, FT3, FT4, HTG, TG-Ab, TPO-Ab in case group were significantly higher than the control group (P<0.05. Right calcaneal speed of sound (SOS in case group was significantly lower than the control group (P<0.05, BGP, PTH in case group were significantly higher than the control group (P<0.05. Conclusions: Hyperthyroidism can cause thyroid hormone levels abnormal, abnormal increase autoantibodies, decrease bone density, bone metabolism actively, easy to form osteoporosis, clinical treatment of hyperthyroidism in the same time, should actively prevent the occurrence of osteoporosis

  16. Plasma Zonulin and its Association with Kidney Function, Severity of Heart Failure, and Metabolic Inflammation.

    Dschietzig, Thomas B; Boschann, Felix; Ruppert, Jana; Armbruster, Franz P; Meinitzer, Andreas; Bankovic, Dragic; Mitrovic, Veselin; Melzer, Christoph

    2016-12-01

    The tight junction regulator zonulin has attracted clinical attention as a biomarker of increased gastrointestinal permeability. Recent work also suggests zonulin to represent a general regulator of tissue barriers and a player in metabolic inflammation. Here, we investigated the associations of zonulin with chronic heart failure (CHF), kidney function, and metabolic inflammation. Using multiple linear regression (Generalized Linear Model), this study determined the association of plasma zonulin with different laboratory and clinical parameters in 225 patients carrying automatic implantable cardioverters/defibrillators (AICD) for primary or secondary prevention. In another 115 patients with diastolic or systolic CHF, we investigated a possible relationship between zonulin and CHF severity. In the AICD cohort, zonulin associated inversely with serum creatinine (p = 0.013), carboxymethyl-lysine calprotectin (p zonulin increased significantly with high-sensitivity CRP (p = 0.014). In the CHF cohort, we found a highly significant rise of NT-proBNP, but not of zonulin with NYHA functional classes I-IV or other parameters of CHF severity. The inverse associations of zonulin with creatinine and markers of cardio-vascular risk (high CMLcalprotectin and kynurenine, low homoarginine) are novel findings that need further experimental and clinical clarification. Our study indicates zonulin involvement in metabolic inflammation in T2D, but no association with disease status in CHF.

  17. Metabolic Syndrome, Strain, and Reduced Myocardial Function: Multi-Ethnic Study of Atherosclerosis

    Almeida, André Luiz Cerqueira de, E-mail: andrealmeida@cardiol.br [Johns Hopkins University, Baltimore, MD (United States); Universidade Estadual de Feira de Santana, Bahia (Brazil); Teixido-Tura, Gisela; Choi, Eui-Young; Opdahl, Anders; Fernandes, Verônica R. S. [Johns Hopkins University, Baltimore, MD (United States); Wu, Colin O. [National Heart, Lung and Blood Institute, Bethesda, MD (United States); Bluemke, David A. [National Institutes of Health Clinical Center, National Institute for Biomedical Imaging and Bioengineering, Bethesda, MD (United States); Lima, João A. C. [Johns Hopkins University, Baltimore, MD (United States)

    2014-04-15

    Subclinical cardiovascular disease is prevalent in patients with Metabolic Syndrome (MetSyn). Left ventricular (LV) circumferential strain (ε{sub CC}) and longitudinal strain (ε{sub LL}), assessed by Speckle Tracking Echocardiography (STE), are indices of systolic function: shortening is indicated by negative strain, and thus, the more negative the strain, the better the LV systolic function. They have been used to demonstrate subclinical ventricular dysfunction in several clinical disorders. We hypothesized that MetSyn is associated with impaired myocardial function, as assessed by STE. We analyzed Multi-Ethnic Study of Atherosclerosis (MESA) participants who underwent STE and were evaluated for all MetSyn components. Among the 133 participants included [women: 63%; age: 65 ± 9 years (mean ± SD)], the prevalence of MetSyn was 31% (41/133). Individuals with MetSyn had lower ε{sub CC} and lower ε{sub LL} than those without MetSyn (-16.3% ± 3.5% vs. -18.4% ± 3.7%, p < 0.01; and -12.1% ± 2.5% vs. -13.9% ± 2.3%, p < 0.01, respectively). The LV ejection fraction (LVEF) was similar in both groups (p = 0.09). In multivariate analysis, MetSyn was associated with less circumferential myocardial shortening as indicated by less negative ε{sub CC} (B = 2.1%, 95%CI:0.6 3.5, p < 0.01) even after adjusting for age, ethnicity, LV mass, and LVEF). Likewise, presence of MetSyn (B = 1.3%, 95%CI:0.3 2.2, p < 0.01) and LV mass (B = 0.02%, 95% CI: 0.01-0.03, p = 0.02) were significantly associated with less longitudinal myocardial shortening as indicated by less negative ε{sub LL} after adjustment for ethnicity, LVEF, and creatinine. Left ventricular ε{sub CC} and ε{sub LL}, markers of subclinical cardiovascular disease, are impaired in asymptomatic individuals with MetSyn and no history of myocardial infarction, heart failure, and/or LVEF < 50%.

  18. Metabolic Syndrome, Strain, and Reduced Myocardial Function: Multi-Ethnic Study of Atherosclerosis

    Almeida, André Luiz Cerqueira de; Teixido-Tura, Gisela; Choi, Eui-Young; Opdahl, Anders; Fernandes, Verônica R. S.; Wu, Colin O.; Bluemke, David A.; Lima, João A. C.

    2014-01-01

    Subclinical cardiovascular disease is prevalent in patients with Metabolic Syndrome (MetSyn). Left ventricular (LV) circumferential strain (ε CC ) and longitudinal strain (ε LL ), assessed by Speckle Tracking Echocardiography (STE), are indices of systolic function: shortening is indicated by negative strain, and thus, the more negative the strain, the better the LV systolic function. They have been used to demonstrate subclinical ventricular dysfunction in several clinical disorders. We hypothesized that MetSyn is associated with impaired myocardial function, as assessed by STE. We analyzed Multi-Ethnic Study of Atherosclerosis (MESA) participants who underwent STE and were evaluated for all MetSyn components. Among the 133 participants included [women: 63%; age: 65 ± 9 years (mean ± SD)], the prevalence of MetSyn was 31% (41/133). Individuals with MetSyn had lower ε CC and lower ε LL than those without MetSyn (-16.3% ± 3.5% vs. -18.4% ± 3.7%, p < 0.01; and -12.1% ± 2.5% vs. -13.9% ± 2.3%, p < 0.01, respectively). The LV ejection fraction (LVEF) was similar in both groups (p = 0.09). In multivariate analysis, MetSyn was associated with less circumferential myocardial shortening as indicated by less negative ε CC (B = 2.1%, 95%CI:0.6 3.5, p < 0.01) even after adjusting for age, ethnicity, LV mass, and LVEF). Likewise, presence of MetSyn (B = 1.3%, 95%CI:0.3 2.2, p < 0.01) and LV mass (B = 0.02%, 95% CI: 0.01-0.03, p = 0.02) were significantly associated with less longitudinal myocardial shortening as indicated by less negative ε LL after adjustment for ethnicity, LVEF, and creatinine. Left ventricular ε CC and ε LL , markers of subclinical cardiovascular disease, are impaired in asymptomatic individuals with MetSyn and no history of myocardial infarction, heart failure, and/or LVEF < 50%

  19. A radiopharmaceutical for pancreatic exocrine functional diagnosis: 62Zn-EDDA metabolism in pancreas.

    Fujibayashi, Y; Saji, H; Kawai, K; Unuma, Y; Miyata, S; Okuno, T; Hosotani, R; Inoue, K; Adachi, H; Horiuchi, K

    1986-01-01

    The metabolic pathway of radioactive 62Zn-EDDA (ethylenediamine-N,N'-diacetic acid), in the exocrine pancreas was studied with respect to that of endogenous Zn. In pancreatic duct cannulated dog, the secretion of intravenously injected exogenous 62Zn into pancreatic juice increased under the stimulation of CCK-PZ (pancreatic protein secretion stimulating hormone), which closely correlated to endogenous Zn. Moreover, in pancreatic juice, 62Zn as well as endogenous Zn was selectively bound to Zn-metalloenzymes, carboxypeptidase A and B. These results demonstrated the close correlation between the endogenous and the exogenously-administered Zn (62Zn-EDDA), as well as the high availability of 62Zn-EDDA as a marker of pancreatic function for the follow up of carboxypeptidase metabolism.

  20. Hyperpolarized metabolic MR in the study of cardiac function and disease

    Lauritzen, M. H.; Søgaard, L. V.; Madsen, Pia Lisbeth

    2014-01-01

    Several diseases of the heart have been linked to an insufficient ability to generate enough energy (ATP) to sustain proper heart function. Hyperpolarized magnetic resonance (MR) is a novel technique that can visualize and quantify myocardial energy metabolism. Hyperpolarization enhances the MR...... signal from a biological molecule of interest by more than 10,000 times, making it possible to measure its cellular uptake and conversion in specific enzymatic pathways in real time. We review the role of hyperpolarized MR in identifying changes in cardiac metabolism in vivo, and present the extensive...... literature on hyperpolarized pyruvate that has been used to characterize cardiac disease in various in vivo models, such as myocardial ischemia, hypertension, diabetes, hyperthyroidism and heart failure. The technical aspects of the technique are presented as well as the challenges of translating...

  1. Synthesis, secretion, function, metabolism and application of natriuretic peptides in heart failure.

    Fu, Shihui; Ping, Ping; Wang, Fengqi; Luo, Leiming

    2018-01-01

    As a family of hormones with pleiotropic effects, natriuretic peptide (NP) system includes atrial NP (ANP), B-type NP (BNP), C-type NP (CNP), dendroaspis NP and urodilatin, with NP receptor-A (guanylate cyclase-A), NP receptor-B (guanylate cyclase-B) and NP receptor-C (clearance receptor). These peptides are genetically distinct, but structurally and functionally related for regulating circulatory homeostasis in vertebrates. In humans, ANP and BNP are encoded by NP precursor A (NPPA) and NPPB genes on chromosome 1, whereas CNP is encoded by NPPC on chromosome 2. NPs are synthesized and secreted through certain mechanisms by cardiomyocytes, fibroblasts, endotheliocytes, immune cells (neutrophils, T-cells and macrophages) and immature cells (embryonic stem cells, muscle satellite cells and cardiac precursor cells). They are mainly produced by cardiovascular, brain and renal tissues in response to wall stretch and other causes. NPs provide natriuresis, diuresis, vasodilation, antiproliferation, antihypertrophy, antifibrosis and other cardiometabolic protection. NPs represent body's own antihypertensive system, and provide compensatory protection to counterbalance vasoconstrictor-mitogenic-sodium retaining hormones, released by renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system (SNS). NPs play central roles in regulation of heart failure (HF), and are inactivated through not only NP receptor-C, but also neutral endopeptidase (NEP), dipeptidyl peptidase-4 and insulin degrading enzyme. Both BNP and N-terminal proBNP are useful biomarkers to not only make the diagnosis and assess the severity of HF, but also guide the therapy and predict the prognosis in patients with HF. Current NP-augmenting strategies include the synthesis of NPs or agonists to increase NP bioactivity and inhibition of NEP to reduce NP breakdown. Nesiritide has been established as an available therapy, and angiotensin receptor blocker NEP inhibitor (ARNI, LCZ696) has obtained

  2. Detection of Metabolism Function of Microbial Community of Corpses by Biolog-Eco Method.

    Jiang, X Y; Wang, J F; Zhu, G H; Ma, M Y; Lai, Y; Zhou, H

    2016-06-01

    To detect the changes of microbial community functional diversity of corpses with different postmortem interval (PMI) and to evaluate forensic application value for estimating PMI. The cultivation of microbial community from the anal swabs of a Sus scrofa and a human corpse placed in field environment from 0 to 240 h after death was performed using the Biolog-Eco Microplate and the variations of the absorbance values were also monitored. Combined with the technology of forensic pathology and flies succession, the metabolic characteristics and changes of microbial community on the decomposed corpse under natural environment were also observed. The diversity of microbial metabolism function was found to be negatively correlated with the number of maggots in the corpses. The freezing processing had the greatest impact on average well color development value at 0 h and the impact almost disappeared after 48 h. The diversity of microbial metabolism of the samples became relatively unstable after 192 h. The principal component analysis showed that 31 carbon sources could be consolidated for 5 principal components (accumulative contribution ratio >90%).The carbon source tsquare-analysis showed that N -acetyl- D -glucosamine and L -serine were the dominant carbon sources for estimating the PMI (0=240 h) of the Sus scrofa and human corpse. The Biolog-Eco method can be used to reveal the metabolic differences of the carbon resources utilization of the microbial community on the corpses during 0-240 h after death, which could provide a new basis for estimating the PMI. Copyright© by the Editorial Department of Journal of Forensic Medicine

  3. Glucose ameliorates the metabolic profile and mitochondrial function of platelet concentrates during storage in autologous plasma

    Amorini, Angela M.; Tuttobene, Michele; Tomasello, Flora M.; Biazzo, Filomena; Gullotta, Stefano; De Pinto, Vito; Lazzarino, Giuseppe; Tavazzi, Barbara

    2013-01-01

    Background It is essential that the quality of platelet metabolism and function remains high during storage in order to ensure the clinical effectiveness of a platelet transfusion. New storage conditions and additives are constantly evaluated in order to achieve this. Using glucose as a substrate is controversial because of its potential connection with increased lactate production and decreased pH, both parameters triggering the platelet lesion during storage. Materials and methods In this study, we analysed the morphological status and metabolic profile of platelets stored for various periods in autologous plasma enriched with increasing glucose concentrations (13.75, 27.5 and 55 mM). After 0, 2, 4, 6 and 8 days, high energy phosphates (ATP, GTP, ADP, AMP), oxypurines (hypoxanthine, xanthine, uric acid), lactate, pH, mitochondrial function, cell lysis and morphology, were evaluated. Results The data showed a significant dose-dependent improvement of the different parameters in platelets stored with increasing glucose, compared to what detected in controls. Interestingly, this phenomenon was more marked at the highest level of glucose tested and in the period of time generally used for platelet transfusion (0–6 days). Conclusion These results indicate that the addition of glucose during platelet storage ameliorates, in a dose-dependent manner, the biochemical parameters related to energy metabolism and mitochondrial function. Since there was no correspondence between glucose addition, lactate increase and pH decrease in our experiments, it is conceivable that platelet derangement during storage is not directly caused by glucose through an increase of anaerobic glycolysis, but rather to a loss of mitochondrial functions caused by reduced substrate availability. PMID:22682337

  4. Probiotics and Probiotic Metabolic Product Improved Intestinal Function and Ameliorated LPS-Induced Injury in Rats.

    Deng, Bo; Wu, Jie; Li, Xiaohui; Men, Xiaoming; Xu, Ziwei

    2017-11-01

    In the present study, we sought to determine the effects of Bacillus subtilis (BAS) and Bacillus licheniformis (BAL) in rats after lipopolysaccharide (LPS)-induced acute intestinal inflammation. We also determined whether the B. subtilis metabolic product (BASM) is as effective as the live-cell probiotic. 60 male SD rats were randomly assigned to five groups and administered a diet containing 0.05% B. licheniformis (BAL group), 0.05% B. subtilis (BAS group), 0.5% B. subtilis metabolic product (BASM group), or a basic diet (PC group and NC group) for 40 days. On day 40, BAL, BAS, BASM, and NC groups were injected with 4 mg/kg body weight LPS. 4 h later, all rats were anesthetized and sacrificed. The results showed that the administration of B. licheniformis and B. subtilis improved intestinal function as evidenced by histology, increased enzyme activity, and mucosal thickness. They also increased the number of intraepithelial lymphocytes and decreased mucosal myeloperoxidase activity and plasma TNF-α. In addition, the cecal content of B. subtilis-treated rats had significantly increased microbial diversity, decreased numbers of Firmicutes, and increased numbers of Bacteroidetes as compared to rats fed basic diets. Similar to BAS group, the cecal content of B. licheniformis-treated rats decreased the number of Firmicutes. Administration of B. subtilis metabolic product had similar effects on intestinal function, inflammation response, and microbial diversity as B. subtilis but these effects were attenuated. In conclusion, administration of probiotic strains B. licheniformis or B. subtilis improved intestinal function, ameliorated the inflammation response, and modulated microflora after LPS-induced acute inflammation in rats. Non-living cells also exerted probiotic properties but live cells tended to function better.

  5. Delivery Mode and the Transition of Pioneering Gut-Microbiota Structure, Composition and Predicted Metabolic Function

    Noel T. Mueller

    2017-12-01

    Full Text Available Cesarean (C-section delivery, recently shown to cause excess weight gain in mice, perturbs human neonatal gut microbiota development due to the lack of natural mother-to-newborn transfer of microbes. Neonates excrete first the in-utero intestinal content (referred to as meconium hours after birth, followed by intestinal contents reflective of extra-uterine exposure (referred to as transition stool 2 to 3 days after birth. It is not clear when the effect of C-section on the neonatal gut microbiota emerges. We examined bacterial DNA in carefully-collected meconium, and the subsequent transitional stool, from 59 neonates [13 born by scheduled C-section and 46 born by vaginal delivery] in a private hospital in Brazil. Bacterial DNA was extracted, and the V4 region of the 16S rRNA gene was sequenced using the Illumina MiSeq (San Diego, CA, USA platform. We found evidence of bacterial DNA in the majority of meconium samples in our study. The bacterial DNA structure (i.e., beta diversity of meconium differed significantly from that of the transitional stool microbiota. There was a significant reduction in bacterial alpha diversity (e.g., number of observed bacterial species and change in bacterial composition (e.g., reduced Proteobacteria in the transition from meconium to stool. However, changes in predicted microbiota metabolic function from meconium to transitional stool were only observed in vaginally-delivered neonates. Within sample comparisons showed that delivery mode was significantly associated with bacterial structure, composition and predicted microbiota metabolic function in transitional-stool samples, but not in meconium samples. Specifically, compared to vaginally delivered neonates, the transitional stool of C-section delivered neonates had lower proportions of the genera Bacteroides, Parabacteroides and Clostridium. These differences led to C-section neonates having lower predicted abundance of microbial genes related to metabolism of

  6. Comparative effect of olmesartan and candesartan on lipid metabolism and renal function in patients with hypertension: a retrospective observational study

    Nakayama Tomohiro

    2011-08-01

    Full Text Available Abstract Background Angiotensin II receptor blockers (ARBs, including olmesartan and candesartan, are widely used antihypertensive agents. Many clinical studies have demonstrated that ARBs have organ-protecting effects, e.g., cardioprotection, vasculoprotection and renoprotection. However, the effect of prolonged olmesartan monotherapy on lipid metabolism in patients with hypertension is less well studied. We performed a retrospective observational study to compare the effects of olmesartan with those of candesartan, focusing on lipid metabolism and renal function. Methods We used data from the Clinical Data Warehouse of Nihon University School of Medicine obtained between Nov 1, 2004 and Feb 28, 2011, to identify cohorts of new olmesartan users (n = 168 and candesartan users (n = 266. We used propensity-score weighting to adjust for differences in all covariates (age, sex, comorbid diseases, previous drugs between olmesartan and candesartan users, and compared serum chemical data including serum triglyceride (TG, LDL-cholesterol (LDL-C, total cholesterol (TC, potassium, creatinine and urea nitrogen. The mean exposure of olmesartan and candesartan users was 126.1 and 122.8 days, respectively. Results After adjustment, there were no statistically significant differences in all covariates between olmesartan and candesartan users. The mean age was 60.7 and 61.0 years, and 33.4% and 33.7% of olmesartan and candesartan users were women, respectively. There were no statistically significant differences in mean values for all laboratory tests between baseline and during the exposure period in both olmesartan and candesartan users. In olmesartan users, the reduction of serum TG level was significant in comparison with that in candesartan users. Other parameters of lipid profile and renal function showed no statistically significant difference in the change from baseline to during the exposure period between olmesartan and candesartan users. Conclusions

  7. Thyroid peroxidase antibodies in pregnant women with type 1 diabetes: impact on thyroid function, metabolic control and pregnancy outcome

    Vestgaard, Marianne; Nielsen, Lene Ringholm; Rasmussen, Åse Krogh

    2008-01-01

    In pregnant women with type 1 diabetes, we evaluated whether the presence of thyroid peroxidase autoantibodies (anti-TPO) was associated with changes in thyroid function, metabolic control and pregnancy outcome....

  8. Intraspecific variation in flight metabolic rate in the bumblebee Bombus impatiens: repeatability and functional determinants in workers and drones.

    Darveau, Charles-A; Billardon, Fannie; Bélanger, Kasandra

    2014-02-15

    The evolution of flight energetics requires that phenotypes be variable, repeatable and heritable. We studied intraspecific variation in flight energetics in order to assess the repeatability of flight metabolic rate and wingbeat frequency, as well as the functional basis of phenotypic variation in workers and drones of the bumblebee species Bombus impatiens. We showed that flight metabolic rate and wingbeat frequency were highly repeatable in workers, even when controlling for body mass variation using residual analysis. We did not detect significant repeatability in drones, but a smaller range of variation might have prevented us from finding significant values in our sample. Based on our results and previous findings, we associated the high repeatability of flight phenotypes in workers to the functional links between body mass, thorax mass, wing size, wingbeat frequency and metabolic rate. Moreover, differences between workers and drones were as predicted from these functional associations, where drones had larger wings for their size, lower wingbeat frequency and lower flight metabolic rate. We also investigated thoracic muscle metabolic phenotypes by measuring the activity of carbohydrate metabolism enzymes, and we found positive correlations between mass-independent metabolic rate and the activity of all enzymes measured, but in workers only. When comparing workers and drones that differ in flight metabolic rate, only the activity of the enzymes hexokinase and trehalase showed the predicted differences. Overall, our study indicates that there should be correlated evolution among physiological phenotypes at multiple levels of organization and morphological traits associated with flight.

  9. Sequence- and Structure-Based Functional Annotation and Assessment of Metabolic Transporters in Aspergillus oryzae: A Representative Case Study

    Nachon Raethong

    2016-01-01

    Full Text Available Aspergillus oryzae is widely used for the industrial production of enzymes. In A. oryzae metabolism, transporters appear to play crucial roles in controlling the flux of molecules for energy generation, nutrients delivery, and waste elimination in the cell. While the A. oryzae genome sequence is available, transporter annotation remains limited and thus the connectivity of metabolic networks is incomplete. In this study, we developed a metabolic annotation strategy to understand the relationship between the sequence, structure, and function for annotation of A. oryzae metabolic transporters. Sequence-based analysis with manual curation showed that 58 genes of 12,096 total genes in the A. oryzae genome encoded metabolic transporters. Under consensus integrative databases, 55 unambiguous metabolic transporter genes were distributed into channels and pores (7 genes, electrochemical potential-driven transporters (33 genes, and primary active transporters (15 genes. To reveal the transporter functional role, a combination of homology modeling and molecular dynamics simulation was implemented to assess the relationship between sequence to structure and structure to function. As in the energy metabolism of A. oryzae, the H+-ATPase encoded by the AO090005000842 gene was selected as a representative case study of multilevel linkage annotation. Our developed strategy can be used for enhancing metabolic network reconstruction.

  10. Sequence- and Structure-Based Functional Annotation and Assessment of Metabolic Transporters in Aspergillus oryzae: A Representative Case Study.

    Raethong, Nachon; Wong-Ekkabut, Jirasak; Laoteng, Kobkul; Vongsangnak, Wanwipa

    2016-01-01

    Aspergillus oryzae is widely used for the industrial production of enzymes. In A. oryzae metabolism, transporters appear to play crucial roles in controlling the flux of molecules for energy generation, nutrients delivery, and waste elimination in the cell. While the A. oryzae genome sequence is available, transporter annotation remains limited and thus the connectivity of metabolic networks is incomplete. In this study, we developed a metabolic annotation strategy to understand the relationship between the sequence, structure, and function for annotation of A. oryzae metabolic transporters. Sequence-based analysis with manual curation showed that 58 genes of 12,096 total genes in the A. oryzae genome encoded metabolic transporters. Under consensus integrative databases, 55 unambiguous metabolic transporter genes were distributed into channels and pores (7 genes), electrochemical potential-driven transporters (33 genes), and primary active transporters (15 genes). To reveal the transporter functional role, a combination of homology modeling and molecular dynamics simulation was implemented to assess the relationship between sequence to structure and structure to function. As in the energy metabolism of A. oryzae, the H(+)-ATPase encoded by the AO090005000842 gene was selected as a representative case study of multilevel linkage annotation. Our developed strategy can be used for enhancing metabolic network reconstruction.

  11. Investigation of the performance of fermentation processes using a mathematical model including effects of metabolic bottleneck and toxic product on cells.

    Sriyudthsak, Kansuporn; Shiraishi, Fumihide

    2010-11-01

    A number of recent research studies have focused on theoretical and experimental investigation of a bottleneck in a metabolic reaction network. However, there is no study on how the bottleneck affects the performance of a fermentation process when a product is highly toxic and remarkably influences the growth and death of cells. The present work therefore studies the effect of bottleneck on product concentrations under different product toxicity conditions. A generalized bottleneck model in a fed-batch fermentation is constructed including both the bottleneck and the product influences on cell growth and death. The simulation result reveals that when the toxic product strongly influences the cell growth and death, the final product concentration is hardly changed even if the bottleneck is removed, whereas it is markedly changed by the degree of product toxicity. The performance of an ethanol fermentation process is also discussed as a case example to validate this result. In conclusion, when the product is highly toxic, one cannot expect a significant increase in the final product concentration even if removing the bottleneck; rather, it may be more effective to somehow protect the cells so that they can continuously produce the product. Copyright © 2010 Elsevier Inc. All rights reserved.

  12. Exercise training dose differentially alters muscle and heart capillary density and metabolic functions in an obese rat with metabolic syndrome.

    Machado, Marcus Vinicius; Vieira, Aline Bomfim; da Conceição, Fabiana Gomes; Nascimento, Alessandro Rodrigues; da Nóbrega, Antonio Claudio Lucas; Tibirica, Eduardo

    2017-12-01

    What is the central question of this study? Regular exercise is recommended as a non-pharmacological approach for the prevention and treatment of metabolic syndrome. However, the impact of different combinations of intensity, duration and frequency of exercise on metabolic syndrome and microvascular density has not been reported. What is the main finding and its importance? We provide evidence on the impact of aerobic exercise dose on metabolic and microvascular alterations in an experimental model of metabolic syndrome induced by high-fat diet. We found that the exercise frequency and duration were the main factors affecting anthropometric and metabolic parameters and microvascular density in the skeletal muscle. Exercise intensity was related only to microvascular density in the heart. We evaluated the effect of the frequency, duration and intensity of exercise training on metabolic parameters and structural capillary density in obese rats with metabolic syndrome. Wistar-Kyoto rats were fed either a standard commercial diet (CON) or a high-fat diet (HFD). Animals that received the HFD were randomly separated into either a sedentary (SED) group or eight different exercise groups that varied according to the frequency, duration and intensity of training. After 12 weeks of aerobic exercise training, the body composition, aerobic capacity, haemodynamic variables, metabolic parameters and capillary density in the heart and skeletal muscle were evaluated. All the exercise training groups showed reduced resting systolic blood pressure and heart rate and normalized fasting glucose. The minimal amount of exercise (90 min per week) produced little effect on metabolic syndrome parameters. A moderate amount of exercise (150 min per week) was required to reduce body weight and improve capillary density. However, only the high amount of exercise (300 min per week) significantly reduced the amount of body fat depots. The three-way ANOVA showed a main effect of exercise

  13. [Possible effect of E-selectine on structure and function of arterial vessels in patients with metabolic syndrome].

    Voloshyna, O O; Lyzohub, V H; Romanenko, I M

    2007-01-01

    Endothelial dysfunction and endothelial cells activation as it was shown in patients with ischemic heart disease play important role in atherosclerosis progression and the development of cardiovascular events. Relationship between E-selectine and functional/ structural changes of the arterial vessels in patients with metabolic syndrome was not explored. We revealed that both activation of the endothelial cells and structural/functional changes of the arterial wall mostly depend on obesity and dislipedemia and in less extent on carbohydrates metabolism disorders.

  14. Genome-Enabled Modeling of Biogeochemical Processes Predicts Metabolic Dependencies that Connect the Relative Fitness of Microbial Functional Guilds

    Brodie, E.; King, E.; Molins, S.; Karaoz, U.; Steefel, C. I.; Banfield, J. F.; Beller, H. R.; Anantharaman, K.; Ligocki, T. J.; Trebotich, D.

    2015-12-01

    with genome-enabled reactive flow and transport we simulated the importance of pore network properties including connectivity in regulating metabolic interdependencies between microbial functional guilds.

  15. Metabolic liver function measured in vivo by dynamic (18)F-FDGal PET/CT without arterial blood sampling.

    Horsager, Jacob; Munk, Ole Lajord; Sørensen, Michael

    2015-01-01

    Metabolic liver function can be measured by dynamic PET/CT with the radio-labelled galactose-analogue 2-[(18)F]fluoro-2-deoxy-D-galactose ((18)F-FDGal) in terms of hepatic systemic clearance of (18)F-FDGal (K, ml blood/ml liver tissue/min). The method requires arterial blood sampling from a radial artery (arterial input function), and the aim of this study was to develop a method for extracting an image-derived, non-invasive input function from a volume of interest (VOI). Dynamic (18)F-FDGal PET/CT data from 16 subjects without liver disease (healthy subjects) and 16 patients with liver cirrhosis were included in the study. Five different input VOIs were tested: four in the abdominal aorta and one in the left ventricle of the heart. Arterial input function from manual blood sampling was available for all subjects. K*-values were calculated using time-activity curves (TACs) from each VOI as input and compared to the K-value calculated using arterial blood samples as input. Each input VOI was tested on PET data reconstructed with and without resolution modelling. All five image-derived input VOIs yielded K*-values that correlated significantly with K calculated using arterial blood samples. Furthermore, TACs from two different VOIs yielded K*-values that did not statistically deviate from K calculated using arterial blood samples. A semicircle drawn in the posterior part of the abdominal aorta was the only VOI that was successful for both healthy subjects and patients as well as for PET data reconstructed with and without resolution modelling. Metabolic liver function using (18)F-FDGal PET/CT can be measured without arterial blood samples by using input data from a semicircle VOI drawn in the posterior part of the abdominal aorta.

  16. The emerging functionality of endogenous lectins: A primer to the concept and a case study on galectins including medical implications.

    Gabius, Hans-Joachim; Wu, Albert M

    2006-01-01

    Biochemistry textbooks commonly make it appear that it is a foregone conclusion that the hardware of biological information storage and transfer is confined to nucleotides and amino acids, the letters of the genetic code. However, the remarkable talents of a third class of biomolecules are often overlooked. For example, one of them far surpasses the building blocks of nucleic acids and proteins in terms of theoretical coding capacity by oligomer formation. Although often exclusively assigned to duties in energy metabolism, carbohydrates as part of cellular glycoconjugates (glycoproteins, proteoglycans, glycolipids) have, in fact, other important tasks. Currently, they are increasingly gaining recognition as an operative high-density information coding system. An elaborate enzymatic machinery enables cells to be versatile enough to produce a glycan profile (glycome) that is as characteristic as a fingerprint. Moreover, swift modifications during dynamic processes, such as differentiation or malignant transformation, are readily possible. The translation of the information presented in oligosaccharide determinants to biological responses is carried out by lectins. Recognition of foreign glycosignatures in innate immunity, regulation of cell-cell/matrix interactions, cell migration or growth, and intra- and intercellular glycan routing etc represent physiologically far-reaching lectin-carbohydrate functionality. The classification of endogenous lectins is guided by sequence alignments and conservation of distinct structural traits. For example, a jelly-roll-like folding pattern and maintenance of key residue positioning involved in stacking and C-H/pi-interactions as well as directional hydrogen bonds to the 1-galactoside ligands are common denominators among galectins. Biochemical and biophysical studies are beginning to unravel the intricacies of the selection of a limited set of endogenous ligands, such as certain integrins or ganglioside GM1, and combined with

  17. Astrocyte lipid metabolism is critical for synapse development and function in vivo.

    van Deijk, Anne-Lieke F; Camargo, Nutabi; Timmerman, Jaap; Heistek, Tim; Brouwers, Jos F; Mogavero, Floriana; Mansvelder, Huibert D; Smit, August B; Verheijen, Mark H G

    2017-04-01

    The brain is considered to be autonomous in lipid synthesis with astrocytes producing lipids far more efficiently than neurons. Accordingly, it is generally assumed that astrocyte-derived lipids are taken up by neurons to support synapse formation and function. Initial confirmation of this assumption has been obtained in cell cultures, but whether astrocyte-derived lipids support synapses in vivo is not known. Here, we address this issue and determined the role of astrocyte lipid metabolism in hippocampal synapse formation and function in vivo. Hippocampal protein expression for the sterol regulatory element-binding protein (SREBP) and its target gene fatty acid synthase (Fasn) was found in astrocytes but not in neurons. Diminishing SREBP activity in astrocytes using mice in which the SREBP cleavage-activating protein (SCAP) was deleted from GFAP-expressing cells resulted in decreased cholesterol and phospholipid secretion by astrocytes. Interestingly, SCAP mutant mice showed more immature synapses, lower presynaptic protein SNAP-25 levels as well as reduced numbers of synaptic vesicles, indicating impaired development of the presynaptic terminal. Accordingly, hippocampal short-term and long-term synaptic plasticity were defective in mutant mice. These findings establish a critical role for astrocyte lipid metabolism in presynaptic terminal development and function in vivo. GLIA 2017;65:670-682. © 2017 Wiley Periodicals, Inc.

  18. The Deubiquitylase MATH-33 Controls DAF-16 Stability and Function in Metabolism and Longevity.

    Heimbucher, Thomas; Liu, Zheng; Bossard, Carine; McCloskey, Richard; Carrano, Andrea C; Riedel, Christian G; Tanasa, Bogdan; Klammt, Christian; Fonslow, Bryan R; Riera, Celine E; Lillemeier, Bjorn F; Kemphues, Kenneth; Yates, John R; O'Shea, Clodagh; Hunter, Tony; Dillin, Andrew

    2015-07-07

    FOXO family transcription factors are downstream effectors of Insulin/IGF-1 signaling (IIS) and major determinants of aging in organisms ranging from worms to man. The molecular mechanisms that actively promote DAF16/FOXO stability and function are unknown. Here we identify the deubiquitylating enzyme MATH-33 as an essential DAF-16 regulator in IIS, which stabilizes active DAF-16 protein levels and, as a consequence, influences DAF-16 functions, such as metabolism, stress response, and longevity in C. elegans. MATH-33 associates with DAF-16 in cellulo and in vitro. MATH-33 functions as a deubiquitylase by actively removing ubiquitin moieties from DAF-16, thus counteracting the action of the RLE-1 E3-ubiquitin ligase. Our findings support a model in which MATH-33 promotes DAF-16 stability in response to decreased IIS by directly modulating its ubiquitylation state, suggesting that regulated oscillations in the stability of DAF-16 protein play an integral role in controlling processes such as metabolism and longevity. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. The Effect of Marine Derived n-3 Fatty Acids on Adipose Tissue Metabolism and Function

    Marijana Todorčević

    2015-12-01

    Full Text Available Adipose tissue function is key determinant of metabolic health, with specific nutrients being suggested to play a role in tissue metabolism. One such group of nutrients are the n-3 fatty acids, specifically eicosapentaenoic acid (EPA; 20:5n-3 and docosahexaenoic acid (DHA; 22:6n-3. Results from studies where human, animal and cellular models have been utilised to investigate the effects of EPA and/or DHA on white adipose tissue/adipocytes suggest anti-obesity and anti-inflammatory effects. We review here evidence for these effects, specifically focusing on studies that provide some insight into metabolic pathways or processes. Of note, limited work has been undertaken investigating the effects of EPA and DHA on white adipose tissue in humans whilst more work has been undertaken using animal and cellular models. Taken together it would appear that EPA and DHA have a positive effect on lowering lipogenesis, increasing lipolysis and decreasing inflammation, all of which would be beneficial for adipose tissue biology. What remains to be elucidated is the duration and dose required to see a favourable effect of EPA and DHA in vivo in humans, across a range of adiposity.

  20. Assessment of adjuvant ademetionine therapy for the bilirubin metabolism and target organ function of neonatal jaundice

    Fang Xu

    2017-11-01

    Full Text Available Objective: To study the effect of adjuvant ademetionine (SAMe therapy on the bilirubin metabolism and target organ function of neonatal jaundice. Methods: A total of 68 children who were diagnosed with neonatal jaundice in Hubei Jianghan Oilfield General Hospital between March 2015 and April 2017 were selected as the research subjects and randomly divided into the SAMe group who received ademetionine combined with blue ray irradiation and the control group who received blue ray irradiation. The serum contents of bilirubin metabolism indexes and target organ injury markers before treatment as well as 3 d and 7 d after treatment. Results: 3 d and 7 d after treatment, serum TBIL, ALT, AST, GGT, TBA, CK-MB, cTnT, MYO, HBDH, NSE, S100B and GFAP levels of both groups were lower than those before treatment, and serum TBIL, ALT, AST, GGT, TBA, CK-MB, cTnT, MYO, HBDH, NSE, S100B and GFAP levels of SAMe group were lower than those of control group. Conclusion: Adjuvant ademetionine therapy can improve the bilirubin metabolism of neonatal jaundice and reduce the central nerve, myocardial and liver injury.

  1. Positron emission tomographic scan investigations of Huntington's disease: cerebral metabolic correlates of cognitive function

    Berent, S.; Giordani, B.; Lehtinen, S.; Markel, D.; Penney, J.B.; Buchtel, H.A.; Starosta-Rubinstein, S.; Hichwa, R.; Young, A.B.

    1988-01-01

    Fifteen drug-free patients with early to mid-stage Huntington's disease (HD) were evaluated with positron emission tomographic (PET) scans of 18 F-2-fluoro-2-deoxy-D-glucose uptake and quantitative measures of neurological function, learning, memory, and general intelligence. In comparison with a group of normal volunteers, the HD patients showed lower metabolism in both caudate (p less than 0.001) and putamen (p less than 0.001) on PET scans. A significant and positive relationship was found between neuropsychological measures of verbal learning and memory and caudate metabolism in the patient group but not in the normal group. Visual-spatial learning did not reflect a similar pattern, but performance intelligence quotient was positively related to both caudate and putamen metabolism in the HD group. Vocabulary level was unrelated to either brain structure. Discussion focuses on these and other observed brain-behavior relationships and on the implications of these findings for general behaviors such as those involved in coping and adaptation

  2. Tributyltin chloride leads to adiposity and impairs metabolic functions in the rat liver and pancreas.

    Bertuloso, Bruno D; Podratz, Priscila L; Merlo, Eduardo; de Araújo, Julia F P; Lima, Leandro C F; de Miguel, Emilio C; de Souza, Leticia N; Gava, Agata L; de Oliveira, Miriane; Miranda-Alves, Leandro; Carneiro, Maria T W D; Nogueira, Celia R; Graceli, Jones B

    2015-05-19

    Tributyltin chloride (TBT) is an environmental contaminant used in antifouling paints of boats. Endocrine disruptor effects of TBT are well established in animal models. However, the adverse effects on metabolism are less well understood. The toxicity of TBT in the white adipose tissue (WAT), liver and pancreas of female rats were assessed. Animals were divided into control and TBT (0.1 μg/kg/day) groups. TBT induced an increase in the body weight of the rats by the 15th day of oral exposure. The weight gain was associated with high parametrial (PR) and retroperitoneal (RP) WAT weights. TBT-treatment increased the adiposity, inflammation and expression of ERα and PPARγ proteins in both RP and PR WAT. In 3T3-L1 cells, estrogen treatment reduced lipid droplets accumulation, however increased the ERα protein expression. In contrast, TBT-treatment increased the lipid accumulation and reduced the ERα expression. WAT metabolic changes led to hepatic inflammation, lipid accumulation, increase of PPARγ and reduction of ERα protein expression. Accordingly, there were increases in the glucose tolerance and insulin sensitivity tests with increases in the number of pancreatic islets and insulin levels. These findings suggest that TBT leads to adiposity in WAT specifically, impairing the metabolic functions of the liver and pancreas. Copyright © 2015. Published by Elsevier Ireland Ltd.

  3. FoxO3A promotes metabolic adaptation to hypoxia by antagonizing Myc function

    Jensen, Kim Steen; Binderup, Tina; Jensen, Klaus Thorleif

    2011-01-01

    Exposure of metazoan organisms to hypoxia engages a metabolic switch orchestrated by the hypoxia-inducible factor 1 (HIF-1). HIF-1 mediates induction of glycolysis and active repression of mitochondrial respiration that reduces oxygen consumption and inhibits the production of potentially harmful...... tumour tissue in vivo and that FoxO3A short-hairpin RNA (shRNA)-expressing xenograft tumours are decreased in size and metabolically changed. Our findings define a novel mechanism by which FoxO3A promotes metabolic adaptation and stress resistance in hypoxia....... reactive oxygen species (ROS). Here, we show that FoxO3A is activated in hypoxia downstream of HIF-1 and mediates the hypoxic repression of a set of nuclear-encoded mitochondrial genes. FoxO3A is required for hypoxic suppression of mitochondrial mass, oxygen consumption, and ROS production and promotes...... cell survival in hypoxia. FoxO3A is recruited to the promoters of nuclear-encoded mitochondrial genes where it directly antagonizes c-Myc function via a mechanism that does not require binding to the consensus FoxO recognition element. Furthermore, we show that FoxO3A is activated in human hypoxic...

  4. Isolated human islets require hyperoxia to maintain islet mass, metabolism, and function.

    Komatsu, Hirotake; Kang, Dongyang; Medrano, Leonard; Barriga, Alyssa; Mendez, Daniel; Rawson, Jeffrey; Omori, Keiko; Ferreri, Kevin; Tai, Yu-Chong; Kandeel, Fouad; Mullen, Yoko

    2016-02-12

    Pancreatic islet transplantation has been recognized as an effective treatment for Type 1 diabetes; however, there is still plenty of room to improve transplantation efficiency. Because islets are metabolically active they require high oxygen to survive; thus hypoxia after transplant is one of the major causes of graft failure. Knowing the optimal oxygen tension for isolated islets would allow a transplant team to provide the best oxygen environment during pre- and post-transplant periods. To address this issue and begin to establish empirically determined guidelines for islet maintenance, we exposed in vitro cultured islets to different partial oxygen pressures (pO2) and assessed changes in islet volume, viability, metabolism, and function. Human islets were cultured for 7 days in different pO2 media corresponding to hypoxia (90 mmHg), normoxia (160 mmHg), and hyerpoxia (270 or 350 mmHg). Compared to normoxia and hypoxia, hyperoxia alleviated the loss of islet volume, maintaining higher islet viability and metabolism as measured by oxygen consumption and glucose-stimulated insulin secretion responses. We predict that maintaining pre- and post-transplanted islets in a hyperoxic environment will alleviate islet volume loss and maintain islet quality thereby improving transplant outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Catalytic function of the mycobacterial binuclear iron monooxygenase in acetone metabolism.

    Furuya, Toshiki; Nakao, Tomomi; Kino, Kuniki

    2015-10-01

    Mycobacteria such as Mycobacterium smegmatis strain mc(2)155 and Mycobacterium goodii strain 12523 are able to grow on acetone and use it as a source of carbon and energy. We previously demonstrated by gene deletion analysis that the mimABCD gene cluster, which encodes a binuclear iron monooxygenase, plays an essential role in acetone metabolism in these mycobacteria. In the present study, we determined the catalytic function of MimABCD in acetone metabolism. Whole-cell assays were performed using Escherichia coli cells expressing the MimABCD complex. When the recombinant E. coli cells were incubated with acetone, a product was detected by gas chromatography (GC) analysis. Based on the retention time and the gas chromatography-mass spectrometry (GC-MS) spectrum, the reaction product was identified as acetol (hydroxyacetone). The recombinant E. coli cells produced 1.02 mM of acetol from acetone within 24 h. Furthermore, we demonstrated that MimABCD also was able to convert methylethylketone (2-butanone) to 1-hydroxy-2-butanone. Although it has long been known that microorganisms such as mycobacteria metabolize acetone via acetol, this study provides the first biochemical evidence for the existence of a microbial enzyme that catalyses the conversion of acetone to acetol. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Fumarate hydratase is a critical metabolic regulator of hematopoietic stem cell functions.

    Guitart, Amelie V; Panagopoulou, Theano I; Villacreces, Arnaud; Vukovic, Milica; Sepulveda, Catarina; Allen, Lewis; Carter, Roderick N; van de Lagemaat, Louie N; Morgan, Marcos; Giles, Peter; Sas, Zuzanna; Gonzalez, Marta Vila; Lawson, Hannah; Paris, Jasmin; Edwards-Hicks, Joy; Schaak, Katrin; Subramani, Chithra; Gezer, Deniz; Armesilla-Diaz, Alejandro; Wills, Jimi; Easterbrook, Aaron; Coman, David; So, Chi Wai Eric; O'Carroll, Donal; Vernimmen, Douglas; Rodrigues, Neil P; Pollard, Patrick J; Morton, Nicholas M; Finch, Andrew; Kranc, Kamil R

    2017-03-06

    Strict regulation of stem cell metabolism is essential for tissue functions and tumor suppression. In this study, we investigated the role of fumarate hydratase (Fh1), a key component of the mitochondrial tricarboxylic acid (TCA) cycle and cytosolic fumarate metabolism, in normal and leukemic hematopoiesis. Hematopoiesis-specific Fh1 deletion (resulting in endogenous fumarate accumulation and a genetic TCA cycle block reflected by decreased maximal mitochondrial respiration) caused lethal fetal liver hematopoietic defects and hematopoietic stem cell (HSC) failure. Reexpression of extramitochondrial Fh1 (which normalized fumarate levels but not maximal mitochondrial respiration) rescued these phenotypes, indicating the causal role of cellular fumarate accumulation. However, HSCs lacking mitochondrial Fh1 (which had normal fumarate levels but defective maximal mitochondrial respiration) failed to self-renew and displayed lymphoid differentiation defects. In contrast, leukemia-initiating cells lacking mitochondrial Fh1 efficiently propagated Meis1 / Hoxa9 -driven leukemia. Thus, we identify novel roles for fumarate metabolism in HSC maintenance and hematopoietic differentiation and reveal a differential requirement for mitochondrial Fh1 in normal hematopoiesis and leukemia propagation. © 2017 Guitart et al.

  7. TRANSAT-- method for detecting the conserved helices of functional RNA structures, including transient, pseudo-knotted and alternative structures.

    Wiebe, Nicholas J P; Meyer, Irmtraud M

    2010-06-24

    The prediction of functional RNA structures has attracted increased interest, as it allows us to study the potential functional roles of many genes. RNA structure prediction methods, however, assume that there is a unique functional RNA structure and also do not predict functional features required for in vivo folding. In order to understand how functional RNA structures form in vivo, we require sophisticated experiments or reliable prediction methods. So far, there exist only a few, experimentally validated transient RNA structures. On the computational side, there exist several computer programs which aim to predict the co-transcriptional folding pathway in vivo, but these make a range of simplifying assumptions and do not capture all features known to influence RNA folding in vivo. We want to investigate if evolutionarily related RNA genes fold in a similar way in vivo. To this end, we have developed a new computational method, Transat, which detects conserved helices of high statistical significance. We introduce the method, present a comprehensive performance evaluation and show that Transat is able to predict the structural features of known reference structures including pseudo-knotted ones as well as those of known alternative structural configurations. Transat can also identify unstructured sub-sequences bound by other molecules and provides evidence for new helices which may define folding pathways, supporting the notion that homologous RNA sequence not only assume a similar reference RNA structure, but also fold similarly. Finally, we show that the structural features predicted by Transat differ from those assuming thermodynamic equilibrium. Unlike the existing methods for predicting folding pathways, our method works in a comparative way. This has the disadvantage of not being able to predict features as function of time, but has the considerable advantage of highlighting conserved features and of not requiring a detailed knowledge of the cellular

  8. Abnormal glucose metabolism in acute myocardial infarction: influence on left ventricular function and prognosis

    Høfsten, Dan E; Løgstrup, Brian B; Møller, Jacob E

    2009-01-01

    tolerance test before discharge. LV function was assessed using echocardiographic measurements (LV end-diastolic volume, LV end-systolic volume, LV ejection fraction, restrictive diastolic filling pattern, early transmitral flow velocity to early diastolic mitral annular velocity ratio [E/e'], and left...... atrial volume index) and by measuring plasma N-terminal pro-B-type natriuretic peptide levels. RESULTS: After adjustment for age and gender, a linear relationship between the degree of abnormal glucose metabolism was observed for each marker of LV dysfunction (p(trend)

  9. Metabolic and functional characterization of effects of developmental temperature in Drosophila melanogaster

    Schou, Mads Fristrup; Kristensen, Torsten Nygaard; Pedersen, Anders

    2017-01-01

    , and in particular, how physiological stress at extreme temperatures may counteract beneficial acclimation responses at benign temperatures. We exposed Drosophila melanogaster to ten developmental temperatures covering their entire permissible temperature range. We obtained metabolic profiles and reaction norms...... for several functional traits: egg-to-adult viability, developmental time, and heat and cold tolerance. Females were more heat tolerant than males, whereas no sexual dimorphism was found in cold tolerance. A group of metabolites, mainly free amino acids, had linear reaction norms. Several energy carrying...

  10. Morning and Evening Blue-Enriched Light Exposure Alters Metabolic Function in Normal Weight Adults.

    Ivy N Cheung

    Full Text Available Increasing evidence points to associations between light-dark exposure patterns, feeding behavior, and metabolism. This study aimed to determine the acute effects of 3 hours of morning versus evening blue-enriched light exposure compared to dim light on hunger, metabolic function, and physiological arousal. Nineteen healthy adults completed this 4-day inpatient protocol under dim light conditions (<20lux. Participants were randomized to 3 hours of blue-enriched light exposure on Day 3 starting either 0.5 hours after wake (n = 9; morning group or 10.5 hours after wake (n = 10; evening group. All participants remained in dim light on Day 2 to serve as their baseline. Subjective hunger and sleepiness scales were collected hourly. Blood was sampled at 30-minute intervals for 4 hours in association with the light exposure period for glucose, insulin, cortisol, leptin, and ghrelin. Homeostatic model assessment of insulin resistance (HOMA-IR and area under the curve (AUC for insulin, glucose, HOMA-IR and cortisol were calculated. Comparisons relative to baseline were done using t-tests and repeated measures ANOVAs. In both the morning and evening groups, insulin total area, HOMA-IR, and HOMA-IR AUC were increased and subjective sleepiness was reduced with blue-enriched light compared to dim light. The evening group, but not the morning group, had significantly higher glucose peak value during blue-enriched light exposure compared to dim light. There were no other significant differences between the morning or the evening groups in response to blue-enriched light exposure. Blue-enriched light exposure acutely alters glucose metabolism and sleepiness, however the mechanisms behind this relationship and its impacts on hunger and appetite regulation remain unclear. These results provide further support for a role of environmental light exposure in the regulation of metabolism.

  11. A high fat diet alters metabolic and bioenergetic function in the brain: A magnetic resonance spectroscopy study.

    Raider, Kayla; Ma, Delin; Harris, Janna L; Fuentes, Isabella; Rogers, Robert S; Wheatley, Joshua L; Geiger, Paige C; Yeh, Hung-Wen; Choi, In-Young; Brooks, William M; Stanford, John A

    2016-07-01

    Diet-induced obesity and associated metabolic effects can lead to neurological dysfunction and increase the risk of developing Alzheimer's disease (AD) and Parkinson's disease (PD). Despite these risks, the effects of a high-fat diet on the central nervous system are not well understood. To better understand the mechanisms underlying the effects of high fat consumption on brain regions affected by AD and PD, we used proton magnetic resonance spectroscopy ((1)H-MRS) to measure neurochemicals in the hippocampus and striatum of rats fed a high fat diet vs. normal low fat chow. We detected lower concentrations of total creatine (tCr) and a lower glutamate-to-glutamine ratio in the hippocampus of high fat rats. Additional effects observed in the hippocampus of high fat rats included higher N-acetylaspartylglutamic acid (NAAG), and lower myo-inositol (mIns) and serine (Ser) concentrations. Post-mortem tissue analyses revealed lower phosphorylated AMP-activated protein kinase (pAMPK) in the striatum but not in the hippocampus of high fat rats. Hippocampal pAMPK levels correlated significantly with tCr, aspartate (Asp), phosphoethanolamine (PE), and taurine (Tau), indicating beneficial effects of AMPK activation on brain metabolic and energetic function, membrane turnover, and edema. A negative correlation between pAMPK and glucose (Glc) indicates a detrimental effect of brain Glc on cellular energy response. Overall, these changes indicate alterations in neurotransmission and in metabolic and bioenergetic function in the hippocampus and in the striatum of rats fed a high fat diet. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Effect of yoga practices on pulmonary function tests including transfer factor of lung for carbon monoxide (TLCO) in asthma patients.

    Singh, Savita; Soni, Ritu; Singh, K P; Tandon, O P

    2012-01-01

    Prana is the energy, when the self-energizing force embraces the body with extension and expansion and control, it is pranayama. It may affect the milieu at the bronchioles and the alveoli particularly at the alveolo-capillary membrane to facilitate diffusion and transport of gases. It may also increase oxygenation at tissue level. Aim of our study is to compare pulmonary functions and diffusion capacity in patients of bronchial asthma before and after yogic intervention of 2 months. Sixty stable asthmatic-patients were randomized into two groups i.e group 1 (Yoga training group) and group 2 (control group). Each group included thirty patients. Lung functions were recorded on all patients at baseline, and then after two months. Group 1 subjects showed a statistically significant improvement (Pincreased significantly. It was concluded that pranayama & yoga breathing and stretching postures are used to increase respiratory stamina, relax the chest muscles, expand the lungs, raise energy levels, and calm the body.

  13. A Copolymer Scaffold Functionalized with Nanodiamond Particles Enhances Osteogenic Metabolic Activity and Bone Regeneration.

    Yassin, Mohammed A; Mustafa, Kamal; Xing, Zhe; Sun, Yang; Fasmer, Kristine Eldevik; Waag, Thilo; Krueger, Anke; Steinmüller-Nethl, Doris; Finne-Wistrand, Anna; Leknes, Knut N

    2017-06-01

    Functionalizing polymer scaffolds with nanodiamond particles (nDPs) has pronounced effect on the surface properties, such as improved wettability, an increased active area and binding sites for cellular attachment and adhesion, and increased ability to immobilize biomolecules by physical adsorption. This study aims to evaluate the effect of poly(l-lactide-co-ε-caprolactone) (poly(LLA-co-CL)) scaffolds, functionalized with nDPs, on bone regeneration in a rat calvarial critical size defect. Poly(LLA-co-CL) scaffolds functionalized with nDPs are also compared with pristine scaffolds with reference to albumin adsorption and seeding efficiency of bone marrow stromal cells (BMSCs). Compared with pristine scaffolds, the experimental scaffolds exhibit a reduction in albumin adsorption and a significant increase in the seeding efficiency of BMSCs (p = 0.027). In the calvarial defects implanted with BMSC-seeded poly(LLA-co-CL)/nDPs scaffolds, live imaging at 12 weeks discloses a significant increase in osteogenic metabolic activity (p = 0.016). Microcomputed tomography, confirmed by histological data, reveals a substantial increase in bone volume (p = 0.021). The results show that compared with conventional poly(LLA-co-CL) scaffolds those functionalized with nDPs promote osteogenic metabolic activity and mineralization capacity. It is concluded that poly(LLA-co-CL) composite matrices functionalized with nDPs enhance osteoconductivity and therefore warrant further study as potential scaffolding material for bone tissue engineering. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Computation of transverse muon-spin relaxation functions including trapping-detrapping reactions, with application to electron-irradiated tantalum

    Doering, K.P.; Aurenz, T.; Herlach, D.; Schaefer, H.E.; Arnold, K.P.; Jacobs, W.; Orth, H.; Haas, N.; Seeger, A.; Max-Planck-Institut fuer Metallforschung, Stuttgart

    1986-01-01

    A new technique for the economical evaluation of transverse muon spin relaxation functions in situations involving μ + trapping at and detrapping from crystal defects is applied to electron-irradiated Ta exhibiting relaxation maxima at about 35 K, 100 K, and 250 K. The long-range μ + diffusion is shown to be limted by traps over the entire temperature range investigated. The (static) relaxation rates for several possible configurations of trapped muons are discussed, including the effect of the simultaneous presence of a proton in a vacancy. (orig.)

  15. Early-Life Exposure to Perfluoroalkyl Substances and Childhood Metabolic Function.

    Fleisch, Abby F; Rifas-Shiman, Sheryl L; Mora, Ana M; Calafat, Antonia M; Ye, Xiaoyun; Luttmann-Gibson, Heike; Gillman, Matthew W; Oken, Emily; Sagiv, Sharon K

    2017-03-01

    Perfluoroalkyl substances (PFASs) are synthetic chemicals that may persist in the environment and in humans. There is a possible association between early-life PFAS exposure and metabolic dysfunction in later life, but data are limited. We studied 665 mother-child pairs in Project Viva, a Boston, Massachusetts-area cohort recruited 1999-2002. We quantified concentrations of PFASs [perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), perfluorohexane sulfonate (PFHxS), and perfluorodecanoate (PFDeA)] in maternal plasma collected at the first prenatal visit (median, 9.6 weeks gestation) and in child plasma from the mid-childhood research visit (median, 7.7 years). We assessed leptin, adiponectin, and homeostatic model assessment of insulin resistance (HOMA-IR) in mid-childhood. We fit covariate-adjusted linear regression models and conducted stratified analyses by child sex. Children with higher PFAS concentrations had lower HOMA-IR [e.g., -10.1% (95% CI: -17.3, -2.3) per interquartile range increment in PFOA]. This inverse association between child PFAS and HOMA-IR was more pronounced in females [e.g., PFOA: -15.6% (95% CI: -25.4, -4.6) vs. -6.1% (95% CI: -16.2, 5.2) for males]. Child PFAS plasma concentrations were not associated with leptin or adiponectin. Prenatal PFAS plasma concentrations were not associated with leptin, adiponectin, or HOMA-IR in offspring. We found no evidence for an adverse effect of early-life PFAS exposure on metabolic function in mid-childhood. In fact, children with higher PFAS concentrations had lower insulin resistance. Citation: Fleisch AF, Rifas-Shiman SL, Mora AM, Calafat AM, Ye X, Luttmann-Gibson H, Gillman MW, Oken E, Sagiv SK. 2017. Early-life exposure to perfluoroalkyl substances and childhood metabolic function. Environ Health Perspect 125:481-487; http://dx.doi.org/10.1289/EHP303.

  16. Effects of resveratrol on memory performance, hippocampal functional connectivity, and glucose metabolism in healthy older adults.

    Witte, A Veronica; Kerti, Lucia; Margulies, Daniel S; Flöel, Agnes

    2014-06-04

    Dietary habits such as caloric restriction or nutrients that mimic these effects may exert beneficial effects on brain aging. The plant-derived polyphenol resveratrol has been shown to increase memory performance in primates; however, interventional studies in older humans are lacking. Here, we tested whether supplementation of resveratrol would enhance memory performance in older adults and addressed potential mechanisms underlying this effect. Twenty-three healthy overweight older individuals that successfully completed 26 weeks of resveratrol intake (200 mg/d) were pairwise matched to 23 participants that received placebo (total n = 46, 18 females, 50-75 years). Before and after the intervention/control period, subjects underwent memory tasks and neuroimaging to assess volume, microstructure, and functional connectivity (FC) of the hippocampus, a key region implicated in memory functions. In addition, anthropometry, glucose and lipid metabolism, inflammation, neurotrophic factors, and vascular parameters were assayed. We observed a significant effect of resveratrol on retention of words over 30 min compared with placebo (p = 0.038). In addition, resveratrol led to significant increases in hippocampal FC, decreases in glycated hemoglobin (HbA1c) and body fat, and increases in leptin compared with placebo (all p memory performance in association with improved glucose metabolism and increased hippocampal FC in older adults. Our findings offer the basis for novel strategies to maintain brain health during aging. Copyright © 2014 the authors 0270-6474/14/347862-09$15.00/0.

  17. A spectroscopic approach toward depression diagnosis: local metabolism meets functional connectivity.

    Demenescu, Liliana Ramona; Colic, Lejla; Li, Meng; Safron, Adam; Biswal, B; Metzger, Coraline Danielle; Li, Shijia; Walter, Martin

    2017-03-01

    Abnormal anterior insula (AI) response and functional connectivity (FC) is associated with depression. In addition to clinical features, such as severity, AI FC and its metabolism further predicted therapeutic response. Abnormal FC between anterior cingulate and AI covaried with reduced glutamate level within cingulate cortex. Recently, deficient glial glutamate conversion was found in AI in major depression disorder (MDD). We therefore postulate a local glutamatergic mechanism in insula cortex of depressive patients, which is correlated with symptoms severity and itself influences AI's network connectivity in MDD. Twenty-five MDD patients and 25 healthy controls (HC) matched on age and sex underwent resting state functional magnetic resonance imaging and magnetic resonance spectroscopy scans. To determine the role of local glutamate-glutamine complex (Glx) ratio on whole brain AI FC, we conducted regression analysis with Glx relative to creatine (Cr) ratio as factor of interest and age, sex, and voxel tissue composition as nuisance factors. We found that in MDD, but not in HC, AI Glx/Cr ratio correlated positively with AI FC to right supramarginal gyrus and negatively with AI FC toward left occipital cortex (p family wise error). AI Glx/Cr level was negatively correlated with HAMD score (p disintegration of insula toward low level and supramodal integration areas, in MDD. While causality cannot directly be inferred from such correlation, our finding helps to define a multilevel network of response-predicting regions based on local metabolism and connectivity strength.

  18. Supraoptic oxytocin and vasopressin neurons function as glucose and metabolic sensors.

    Song, Zhilin; Levin, Barry E; Stevens, Wanida; Sladek, Celia D

    2014-04-01

    Neurons in the supraoptic nuclei (SON) produce oxytocin and vasopressin and express insulin receptors (InsR) and glucokinase. Since oxytocin is an anorexigenic agent and glucokinase and InsR are hallmarks of cells that function as glucose and/or metabolic sensors, we evaluated the effect of glucose, insulin, and their downstream effector ATP-sensitive potassium (KATP) channels on calcium signaling in SON neurons and on oxytocin and vasopressin release from explants of the rat hypothalamo-neurohypophyseal system. We also evaluated the effect of blocking glucokinase and phosphatidylinositol 3 kinase (PI3K; mediates insulin-induced mobilization of glucose transporter, GLUT4) on responses to glucose and insulin. Glucose and insulin increased intracellular calcium ([Ca(2+)]i). The responses were glucokinase and PI3K dependent, respectively. Insulin and glucose alone increased vasopressin release (P glucose in the presence of insulin. The oxytocin (OT) and vasopressin (VP) responses to insulin+glucose were blocked by the glucokinase inhibitor alloxan (4 mM; P ≤ 0.002) and the PI3K inhibitor wortmannin (50 nM; OT: P = 0.03; VP: P ≤ 0.002). Inactivating K ATP channels with 200 nM glibenclamide increased oxytocin and vasopressin release (OT: P neurons functioning as glucose and "metabolic" sensors to participate in appetite regulation.

  19. The exploration of the changes in bone metabolism in patients with abnormal thyroid function

    Chu Shaolin; Li Xiaohong; Lei Qiufang; Ye Peihong; Chai Luhua

    2001-01-01

    To explore the changes in bone metabolism with abnormal thyroid function, BGP and PTH in 91 patients with hyperthyroidism, 37 patients with hypothyroidism, 51 controls, were measured by means of IRMA, calcaneus heel bone density (BMD) was measured by means of 241 Am single photon absorptiometry. BGP levels in hyperthyroidism were significantly higher than those in controls (P < 0.001). BGP levels in hypothyroidism were significantly lower than those in controls (P < 0.001). PTH levels in hyperthyroidism were a little lower than those in controls (P < 0.05). PTH levels in hypothyroidism were significantly higher than those in controls (P < 0.001). The measurement of BMD showed that the prevalence rates of osteoporosis (OP) in hyperthyroidism and hypothyroidism were significantly higher than those in controls. In hyperthyroidism and hypothyroidism groups the age of OP tends to be younger. The patients with hyperthyroidism over 55 years of age were all suffered from OP. The changes in BGP and PTH were earlier than BMD, so BGP and PTH can be used as sensitive indicator of the changes in bone metabolism with abnormal thyroid function, especially for curative effect observations

  20. The in utero programming effect of increased maternal androgens and a direct fetal intervention on liver and metabolic function in adult sheep.

    Hogg, Kirsten; Wood, Charlotte; McNeilly, Alan S; Duncan, W Colin

    2011-01-01

    Epigenetic changes in response to external stimuli are fast emerging as common underlying causes for the pre-disposition to adult disease. Prenatal androgenization is one such model that results in reproductive and metabolic features that are present in conditions such as polycystic ovary syndrome (PCOS). We examined the effect of prenatal androgens on liver function and metabolism of adult sheep. As non-alcoholic fatty liver disease is increased in PCOS we hypothesized that this, and other important liver pathways including metabolic function, insulin-like growth factor (IGF) and steroid receptivity, would be affected. Pregnant ewes received vehicle control (C; n = 5) or testosterone propionate (TP; n = 9) twice weekly (100 mg; i.m) from d62-102 (gestation 147 days). In a novel treatment paradigm, a second cohort received a direct C (n = 4) or TP (20 mg; n = 7) fetal injection at d62 and d82. In adults, maternal TP exposure resulted in increased insulin secretion to glucose load (Pfetal intervention (C and TP) led to early fatty liver changes in all animals without differential changes in insulin secretion. Furthermore, hepatic phosphoenolpyruvate carboxykinase (PEPCK) was up-regulated in the fetal controls (Pfetal TP (Pfetal TP exposure. Adult liver metabolism and signaling can be altered by early exposure to sex steroids implicating epigenetic regulation of metabolic disturbances that are common in PCOS.

  1. Development of baked and extruded functional foods from metabolic syndrome specific ingredient mix.

    Miglani, Neetu; Bains, Kiran; Kaur, Harpreet

    2015-09-01

    The study was aimed to develop baked and extruded functional foods from Metabolic Syndrome (MS) specific designed ingredient mixes with optimum amino acid makeup using key food ingredients with functional properties such as whole cereals, legumes, skimmed milk powder, along with flaxseeds and fenugreek seeds. Two cereals viz. barley and oats and four pulses viz. mung bean, cowpea, bengal gram and soybean were blended in different proportions in order to balance the limiting amino acid lysine in the wheat flour. Three products namely bread, extruded snack and noodles prepared from twenty five ingredient mixes. Six ingredient mixes of breads and four ingredient mixes each of extruded snack and noodles specifically designed for MS patients were organoleptically at par with control wheat flour products. The acceptable products had significantly (p ≤ 0.05) higher lysine, crude protein, ash and fibre and low carbohydrates in compare control whole wheat flour products, hence appropriate for MS patients.

  2. Evidence that the tri-cellular metabolism of N-acetylaspartate functions as the brain's "operating system": how NAA metabolism supports meaningful intercellular frequency-encoded communications.

    Baslow, Morris H

    2010-11-01

    N-acetylaspartate (NAA), an acetylated derivative of L-aspartate (Asp), and N-acetylaspartylglutamate (NAAG), a derivative of NAA and L-glutamate (Glu), are synthesized by neurons in brain. However, neurons cannot catabolize either of these substances, and so their metabolism requires the participation of two other cell types. Neurons release both NAA and NAAG to extra-cellular fluid (ECF) upon stimulation, where astrocytes, the target cells for NAAG, hydrolyze it releasing NAA back into ECF, and oligodendrocytes, the target cells for NAA, hydrolyze it releasing Asp to ECF for recycling to neurons. This sequence is unique as it is the only known amino acid metabolic cycle in brain that requires three cell types for its completion. The results of this cycling are two-fold. First, neuronal metabolic water is transported to ECF for its removal from brain. Second, the rate of neuronal activity is coupled with focal hyperemia, providing stimulated neurons with the energy required for transmission of meaningful frequency-encoded messages. In this paper, it is proposed that the tri-cellular metabolism of NAA functions as the "operating system" of the brain, and is essential for normal cognitive and motor activities. Evidence in support of this hypothesis is provided by the outcomes of two human inborn errors in NAA metabolism.

  3. Changes in body weight, blood pressure and selected metabolic biomarkers with an energy-restricted diet including twice daily sweet snacks and once daily sugar-free beverage

    Nickols-Richardson, Sharon M.; Piehowski, Kathryn E.; Metzgar, Catherine J.; Miller, Debra L.; Preston, Amy G.

    2014-01-01

    BACKGROUND/OBJECTIVES The type of sweet snack incorporated into an energy-restricted diet (ERD) may produce differential effects on metabolic improvements associated with body weight (BW) loss. This study compared effects of incorporating either twice daily energy-controlled dark chocolate snacks plus once daily sugar-free cocoa beverage (DC) to non-chocolate snacks plus sugar-free non-cocoa beverage (NC) into an ERD on BW loss and metabolic outcomes. MATERIALS/METHODS In an 18-week randomize...

  4. Exercise reveals impairments in left ventricular systolic function in patients with metabolic syndrome.

    Fournier, Sara B; Reger, Brian L; Donley, David A; Bonner, Daniel E; Warden, Bradford E; Gharib, Wissam; Failinger, Conard F; Olfert, Melissa D; Frisbee, Jefferson C; Olfert, I Mark; Chantler, Paul D

    2014-01-01

    Metabolic syndrome (MetS) is the manifestation of a cluster of cardiovascular risk factors and is associated with a threefold increase in the risk of cardiovascular morbidity and mortality, which is suggested to be mediated, in part, by resting left ventricular (LV) systolic dysfunction. However, to what extent resting LV systolic function is impaired in MetS is controversial, and there are no data indicating whether LV systolic function is impaired during exercise. Accordingly, the objective of this study was to examine comprehensively the LV and arterial responses to exercise in individuals with MetS without diabetes and/or overt cardiovascular disease in comparison to a healthy control population. Cardiovascular function was characterized using Doppler echocardiography and gas exchange in individuals with MetS (n = 27) versus healthy control subjects (n = 20) at rest and during peak exercise. At rest, individuals with MetS displayed normal LV systolic function but reduced LV diastolic function compared with healthy control subjects. During peak exercise, individuals with MetS had impaired contractility, pump performance and vasodilator reserve capacity versus control subjects. A blunted contractile reserve response resulted in diminished arterial-ventricular coupling reserve and limited aerobic capacity in individuals with MetS versus control subjects. These findings are of clinical importance, because they provide insight into the pathophysiological changes in MetS that may predispose this population of individuals to an increased risk of cardiovascular morbidity and mortality.

  5. Association between functional performance and executive cognitive functions in an elderly population including patients with low ankle–brachial index

    Ferreira NV

    2015-05-01

    Full Text Available Naomi Vidal Ferreira,1 Paulo Jannuzzi Cunha,2 Danielle Irigoyen da Costa,3 Fernando dos Santos,1 Fernando Oliveira Costa,1 Fernanda Consolim-Colombo,4 Maria Cláudia Irigoyen1 1Heart Institute, Medical School, Universidade de São Paulo, São Paulo, SP, Brazil; 2Neuroimaging in Psychiatry Laboratory, Department of Psychiatry, Medical School, Universidade de São Paulo, São Paulo, SP, Brazil; 3Rio Grande do Sul Cardiology Institute, Fundação Universitária de Cardiologia, Porto Alegre, RS, Brazil; 4Medical School, Universidade Nove de Julho, São Paulo, SP, Brazil Introduction: Peripheral arterial disease, as measured by the ankle–brachial index (ABI, is prevalent among the elderly, and is associated with functional performance, assessed by the 6-minute walk test (6MWT. Executive cognitive function (ECF impairments are also prevalent in this population, but no existing study has investigated the association between ECF and functional performance in an elderly population including individuals with low ABI.Aim: To investigate the association between functional performance, as measured by the 6MWT, and loss in ECF, in an elderly sample including individuals with low ABI.Method: The ABI group was formed by 26 elderly individuals with low ABI (mean ABI: 0.63±0.19, and the control group was formed by 40 elderly individuals with normal ABI (mean ABI: 1.08±0.07. We analyzed functional performance using the 6MWT, global cognition using the Mini-Mental State Examination (MMSE, and ECF using the Digit Span for assessing attention span and working memory, the Stroop Color Word Test (SCWT for assessing information processing speed and inhibitory control/impulsivity, and the Controlled Oral Word Association Test (COWAT for assessing semantic verbal fluency and phonemic verbal fluency. We also used a factor analysis on all of the ECF tests (global ECF.Results: Before adjustment, the ABI group performed worse on global cognition, attention span, working

  6. Effects of environmental pollution with aromatic hydrocarbons on endocrine and metabolic functions of the human placenta.

    Wierzba, Waldemar; Radowicki, Stanisław; Bojar, Iwona; Pinkas, Jarosław

    2018-03-14

    Phenol and 1-hydroxypyrene are biological markers of exposure to polycyclic aromatic hydrocarbons (PAH) that have certain negative effects on parenchymal organs such as the human placenta. The literature presents only few reports regarding the effects of elevated PAH levels on the functions of the human placenta. The aim of the work is to assess the effects of elevated PAH levels in excreted urine on the endocrine and metabolic functions of the human placenta obtained from a normal pregnancy. Tissue material from 50 afterbirths from Płock constituted a study group, whereas 50 afterbirths from Kutno constituted a control group. Immunohistochemical reactions with the peroxidase method using LSAB kits (DAKO, Denmark) were performed. The extent and intensity of reactions were analysed. The levels of phenols and 1-hydroxypyrene in the excreted urine of pregnant women (undergoing delivery) were detected using gas chromatography and colorimetry. The statistical analysis used the PQStat v.1.6.2 software; moreover, t-student and chi-square tests were used. Differences were considered to be significant at the significance level of 95% (p<0.05). The levels of phenol and 1-hydroxypyrene in the excreted urine were demonstrated to be statistically significantly higher in patients living in the area of Płock. Statistically lower expression of placental glutathione transferase and lower immunohistochemical demonstration of the placental phosphatase activity were observed in placentas from Płock. It has been demonstrated that the expression of the oestrogen receptor activity and placental gonadotropin is significantly higher in placentas from areas not contaminated with aromatic hydrocarbons (Kutno). The course of pregnancy in the environment with elevated levels of aromatic hydrocarbons leads to impaired placental functioning and reduced endocrine and metabolic activity of the placenta.

  7. Long-term exposure to ambient air pollution (including PM1) and metabolic syndrome: The 33 Communities Chinese Health Study (33CCHS).

    Yang, Bo-Yi; Qian, Zhengmin Min; Li, Shanshan; Fan, Shujun; Chen, Gongbo; Syberg, Kevin M; Xian, Hong; Wang, Si-Quan; Ma, Huimin; Chen, Duo-Hong; Yang, Mo; Liu, Kang-Kang; Zeng, Xiao-Wen; Hu, Li-Wen; Guo, Yuming; Dong, Guang-Hui

    2018-07-01

    Little evidence exists about the effects of long-term exposure to ambient air pollution on metabolic syndrome (MetS). This study aimed to determine the association between long-term ambient air pollution and MetS in China. A total of 15,477 adults who participated in the 33 Communities Chinese Health Study (33CCHS) in 2009 were evaluated. MetS was defined based on the recommendation by the Joint Interim Societies. Exposure to air pollutants was assessed using data from monitoring stations and a spatial statistical model (including particles with diameters ≤ 1.0 µm (PM 1 ), ≤ 2.5 µm (PM 2.5 ), and ≤ 10 µm (PM 10 ), sulfur dioxide (SO 2 ), nitrogen dioxide (NO 2 ), and ozone (O 3 )). Two-level logistic regression analyses were utilized to assess the associations between air pollutants and MetS. The prevalence of MetS was 30.37%. The adjusted odds ratio of MetS per 10 µg/m 3 increase in PM 1 , PM 2.5 , PM 10 , SO 2 , NO 2 , and O 3 were 1.12 (95% CI = 1.00-1.24), 1.09 (95% CI = 1.00-1.18), 1.13 (95% CI = 1.08-1.19), 1.10 (95% CI = 1.02-1.18), 1.33 (95% CI = 1.12-1.57), and 1.10 (95% CI = 1.01-1.18), respectively. Stratified analyses indicated that the above associations were stronger in participants with the demographic variables of males, < 50 years of age, and higher income, as well as with the behavioral characteristics of smoking, drinking, and consuming sugar-sweetened soft drinks frequently. This study indicates that long-term exposure to ambient air pollutants may increase the risk of MetS, especially among males, the young to middle aged, those of low income, and those with unhealthy lifestyles. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. Topiramate improves neurovascular function, epidermal nerve fiber morphology, and metabolism in patients with type 2 diabetes mellitus

    Boyd A

    2010-12-01

    Full Text Available Amanda L Boyd, Patricia M Barlow, Gary L Pittenger, Kathryn F Simmons, Aaron I VinikDepartment of Internal Medicine, Eastern Virginia Medical School, Norfolk, VA, USAPurpose: To assess the effects of topiramate on C-fiber function, nerve fiber morphology, and metabolism (including insulin sensitivity, obesity, and dyslipidemia in type 2 diabetes.Patients and methods: We conducted an 18-week, open-label trial treating patients with topiramate. Twenty subjects with type 2 diabetes and neuropathy (61.5 ± 1.29 years; 15 male, 5 female were enrolled and completed the trial. Neuropathy was evaluated by total neuropathy scores, nerve conduction studies, quantitative sensory tests, laser Doppler skin blood flow, and intraepidermal nerve fibers in skin biopsies.Results: Topiramate treatment improved symptoms compatible with C-fiber dysfunction. Weight, blood pressure, and hemoglobin A1c also improved. Laser Doppler skin blood flow improved significantly after 12 weeks of treatment, but returned to baseline at 18 weeks. After 18 weeks of treatment there was a significant increase in intraepidermal nerve fiber length at the forearm, thigh, and proximal leg. Intraepidermal nerve fiber density was significantly increased by topiramate in the proximal leg.Conclusion: This study is the first to demonstrate that it is possible to induce skin intraepidermal nerve fiber regeneration accompanied by enhancement of neurovascular function, translating into improved symptoms as well as sensory nerve function. The simultaneous improvement of selective metabolic indices may play a role in this effect, but this remains to be determined.Keywords: diabetic neuropathy, skin blood flow, skin biopsy, diabetes

  9. ON A COURNOT DUOPOLY GAME WITH DIFFERENTIATED GOODS, HETEROGENEOUS EXPECTATIONS AND A COST FUNCTION INCLUDING EMISSION COSTS

    Georges SARAFOPOULOS

    2017-07-01

    Full Text Available In this study we investigate the dynamics of a nonlinear Cournot- type duopoly game with differentiated goods, linear demand and a cost function that includes emission costs. The game is modeled with a system of two difference equations. Existence and stability of equilibria of this system are studied. We show that the model gives more complex chaotic and unpredictable trajectories as a consequence of change in the parameter of horizontal product differentiation and a higher (lower degree of product differentiation (weaker or fiercer competition destabilize (stabilize the economy. The chaotic features are justified numerically via computing Lyapunov numbers and sensitive dependence on initial conditions. Also, we show that in this case there are stable trajectories and a higher (lower degree of product differentiation does not tend to destabilize the economy.

  10. An impedance function approach for soil-structure interaction analyses including structure-to-structure interaction effects

    Gantayat, A.; Kamil, H.

    1981-01-01

    The dynamic soil-structure and structure-to-structure interaction effects may be determined in one of the two ways: by modeling the entire soil-structure system by a finite-element model, or by using a frequency-dependent (or frequency-independent) impedance function approach. In seismic design of nuclear power plant structures, the normal practice is to use the first approach because of its simplicity and easy availability of computer codes to perform such analyses. However, in the finite-element approach, because of the size and cost restrictions, the three-dimensional behavior of the entire soil-structure system and the radiation damping in soil are only approximately included by using a two-dimensional finite-element mesh. In using the impedance function approach, the soil-structure analyses can be performed in four steps: (a) determination of the dynamic properties of the fixed base superstructure, (b) determination of foundation and structure impedance matrices and input motions, (c) evaluation of foundation motion, (d) analysis of the fixed base superstructure using computed foundation motion. (orig./RW)

  11. A close link between metabolic activity and functional connectivity in the resting human brain

    Passow, Susanne [Department of Biological and Medical Psychology, University of Bergen (Norway); NORMENT Center of Excellence, University of Oslo (Norway); Specht, Karsten [Department of Biological and Medical Psychology, University of Bergen (Norway); Department of Clinical Engineering, Haukeland University Hospital, Bergen (Norway); Adamsen, Tom Christian [Department of Radiology, Haukeland University Hospital, Bergen (Norway); Department of Chemistry, University of Bergen (Norway); Biermann, Martin; Brekke, Njål [Department of Radiology, Haukeland University Hospital, Bergen (Norway); Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen (Norway); Craven, Alexander Richard [Department of Biological and Medical Psychology, University of Bergen (Norway); NORMENT Center of Excellence, University of Oslo (Norway); Ersland, Lars [Department of Clinical Engineering, Haukeland University Hospital, Bergen (Norway); NORMENT Center of Excellence, University of Oslo (Norway); Grüner, Renate [Department of Radiology, Haukeland University Hospital, Bergen (Norway); Department of Physics and Technology, University of Bergen (Norway); NORMENT Center of Excellence, University of Oslo (Norway); Kleven-Madsen, Nina [Department of Radiology, Haukeland University Hospital, Bergen (Norway); Department of Physics and Technology, University of Bergen (Norway); Kvernenes, Ole-Heine [Department of Radiology, Haukeland University Hospital, Bergen (Norway); Schwarzlmüller, Thomas [Department of Radiology, Haukeland University Hospital, Bergen (Norway); Department of Clinical Medicine, University of Bergen (Norway); Olesen, Rasmus [Center of Functionally Integrative Neuroscience and MINDLab, Aarhus University, Aarhus (Denmark); Hugdahl, Kenneth [Department of Biological and Medical Psychology, University of Bergen (Norway); Department of Radiology, Haukeland University Hospital, Bergen (Norway); Division of Psychiatry, Haukeland University Hospital, Bergen (Norway); NORMENT Center of Excellence, University of Oslo (Norway)

    2015-05-18

    Default-mode network (DMN) functional connectivity and its task-dependent down-regulation have attracted a lot of attention in the field of neuroscience. Nevertheless, the exact underlying mechanisms of DMN functional connectivity, or more specifically, the blood oxygen level-dependent (BOLD) signal, are still not completely understood. To investigate more directly the association between local glucose consumption, local glutamatergic neurotransmission and DMN functional connectivity during rest, the present study combined for the first time 2-Deoxy-2-[18F]fluoroglucose positron emission tomography (FDG-PET), proton magnetic resonance spectroscopy (1H-MRS), and resting-state functional magnetic resonance imaging (rs-fMRI). Seed-based correlation analyses, using a key region of the DMN i.e. the dorsal posterior cingulate cortex as seed, revealed overall striking spatial similarities between fluctuations in FDG-uptake and the BOLD signal. More specifically, a conjunction analysis across both modalities showed that DMN areas as the inferior parietal lobe, angular gyrus, precuneus, middle and medial frontal gyrus were positively correlated with the dorsal posterior cingulate cortex. Furthermore, we could demonstrate that local glucose consumption in the medial frontal gyrus, posterior cingulate cortex and left angular gyrus was associated with functional connectivity within the DMN. We did not find a relationship between glutamatergic neurotransmission and functional connectivity. In line with very recent findings, our results provide further evidence for a close association between local metabolic activity and functional connectivity and enable further insights towards a better understanding of the underlying mechanisms of the BOLD signal.

  12. A close link between metabolic activity and functional connectivity in the resting human brain

    Passow, Susanne; Specht, Karsten; Adamsen, Tom Christian; Biermann, Martin; Brekke, Njål; Craven, Alexander Richard; Ersland, Lars; Grüner, Renate; Kleven-Madsen, Nina; Kvernenes, Ole-Heine; Schwarzlmüller, Thomas; Olesen, Rasmus; Hugdahl, Kenneth

    2015-01-01

    Default-mode network (DMN) functional connectivity and its task-dependent down-regulation have attracted a lot of attention in the field of neuroscience. Nevertheless, the exact underlying mechanisms of DMN functional connectivity, or more specifically, the blood oxygen level-dependent (BOLD) signal, are still not completely understood. To investigate more directly the association between local glucose consumption, local glutamatergic neurotransmission and DMN functional connectivity during rest, the present study combined for the first time 2-Deoxy-2-[18F]fluoroglucose positron emission tomography (FDG-PET), proton magnetic resonance spectroscopy (1H-MRS), and resting-state functional magnetic resonance imaging (rs-fMRI). Seed-based correlation analyses, using a key region of the DMN i.e. the dorsal posterior cingulate cortex as seed, revealed overall striking spatial similarities between fluctuations in FDG-uptake and the BOLD signal. More specifically, a conjunction analysis across both modalities showed that DMN areas as the inferior parietal lobe, angular gyrus, precuneus, middle and medial frontal gyrus were positively correlated with the dorsal posterior cingulate cortex. Furthermore, we could demonstrate that local glucose consumption in the medial frontal gyrus, posterior cingulate cortex and left angular gyrus was associated with functional connectivity within the DMN. We did not find a relationship between glutamatergic neurotransmission and functional connectivity. In line with very recent findings, our results provide further evidence for a close association between local metabolic activity and functional connectivity and enable further insights towards a better understanding of the underlying mechanisms of the BOLD signal.

  13. Fetal Programming of Body Composition, Obesity, and Metabolic Function: The Role of Intrauterine Stress and Stress Biology

    Sonja Entringer

    2012-01-01

    Full Text Available Epidemiological, clinical, physiological, cellular, and molecular evidence suggests that the origins of obesity and metabolic dysfunction can be traced back to intrauterine life and supports an important role for maternal nutrition prior to and during gestation in fetal programming. The elucidation of underlying mechanisms is an area of interest and intense investigation. In this perspectives paper we propose that in addition to maternal nutrition-related processes it may be important to concurrently consider the potential role of intrauterine stress and stress biology. We frame our arguments in the larger context of an evolutionary-developmental perspective that supports roles for both nutrition and stress as key environmental conditions driving natural selection and developmental plasticity. We suggest that intrauterine stress exposure may interact with the nutritional milieu, and that stress biology may represent an underlying mechanism mediating the effects of diverse intrauterine perturbations, including but not limited to maternal nutritional insults (undernutrition and overnutrition, on brain and peripheral targets of programming of body composition, energy balance homeostasis, and metabolic function. We discuss putative maternal-placental-fetal endocrine and immune/inflammatory candidate mechanisms that may underlie the long-term effects of intrauterine stress. We conclude with a commentary of the implications for future research and clinical practice.

  14. Basal Forebrain Cholinergic Deficits Reduce Glucose Metabolism and Function of Cholinergic and GABAergic Systems in the Cingulate Cortex

    Jeong, Da Un; Oh, Jin Hwan; Lee, Ji Eun; Lee, Jihyeon; Cho, Zang Hee; Chang, Jin Woo; Chang, Won Seok

    2015-01-01

    Purpose Reduced brain glucose metabolism and basal forebrain cholinergic neuron degeneration are common features of Alzheimer's disease and have been correlated with memory function. Although regions representing glucose hypometabolism in patients with Alzheimer's disease are targets of cholinergic basal forebrain neurons, the interaction between cholinergic denervation and glucose hypometabolism is still unclear. The aim of the present study was to evaluate glucose metabolism changes caused ...

  15. [Ubiquinone: metabolism and functions. Ubiquinone deficiency and its implication in mitochondrial encephalopathies. Treatment with ubiquinone].

    Artuch, R; Colomé, C; Vilaseca, M A; Pineda, M; Campistol, J

    Review of ubiquinone-10 metabolism and functions in humans, focusing its implication in the pathogenesis and physiopathology of mitochondrial encephalomyopathies. Ubiquinone-10 is an endogenously synthesized lipid with a wide distribution in tissues. Tyrosine and acetil-CoA are involved in ubiquinone biosynthesis. This molecule has several biological functions in cells: it is a movil electron carrier in the mitochondrial respiratory chain and also acts as antioxidant. Owing to its implication in these functions, ubiquinone deficiency may cause important deletereous effects in tissues. Several authors reported ubiquinone deficient status in some physiological and pathological conditions. Mitochondrial encephalomyopathies may be related to a primary or secondary ubiquinone deficient status, or even to an altered function of ubiquinone in the respiratory chain. Moreover, some relevant aspects about ubiquinone therapy in mitochondrial disorders are reported. According to recent reports about ubiquinone implication in several diseases, its determination in different biological samples seems very useful to elucidate the physiopathological mechanisms involved and even the to start a therapy in cases with ubiquinone deficiency.

  16. A Comparative Density Functional Theory and Density Functional Tight Binding Study of Phases of Nitrogen Including a High Energy Density Material N8

    Nicholas Capel

    2015-11-01

    Full Text Available We present a comparative dispersion-corrected Density Functional Theory (DFT and Density Functional Tight Binding (DFTB-D study of several phases of nitrogen, including the well-known alpha, beta, and gamma phases as well as recently discovered highly energetic phases: covalently bound cubic gauche (cg nitrogen and molecular (vdW-bound N8 crystals. Among several tested parametrizations of N–N interactions for DFTB, we identify only one that is suitable for modeling of all these phases. This work therefore establishes the applicability of DFTB-D to studies of phases, including highly metastable phases, of nitrogen, which will be of great use for modelling of dynamics of reactions involving these phases, which may not be practical with DFT due to large required space and time scales. We also derive a dispersion-corrected DFT (DFT-D setup (atom-centered basis parameters and Grimme dispersion parameters tuned for accurate description simultaneously of several nitrogen allotropes including covalently and vdW-bound crystals and including high-energy phases.

  17. Lutein, zeaxanthin and mammalian development: Metabolism, functions and implications for health.

    Giordano, Elena; Quadro, Loredana

    2018-04-11

    It is now widely accepted that nutrition during critical periods in early development, both pre- and postnatal, may have lifetime consequences in determining health or onset of major diseases in the adult life. Dietary carotenoids have shown beneficial health effects throughout the life cycle due to their potential antioxidant properties, their ability to serves as precursors of vitamin A and to the emerging signaling functions of their metabolites. The non-provitamin A carotenoids lutein and zeaxanthin are emerging as important modulators of infant and child visual and cognitive development, as well as critical effectors in the prevention and treatment of morbidity associated with premature births. This review provides a general overview of lutein and zeaxanthin metabolism in mammalian tissues and highlights the major advancements and remaining gaps in knowledge in regards to their metabolism and health effects during pre- and early post-natal development. Furthering our knowledge in this area of research will impact dietary recommendation and supplementation strategies aimed at sustaining proper fetal and infant growth. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Dietary isoflavones alter regulatory behaviors, metabolic hormones and neuroendocrine function in Long-Evans male rats

    Bu Lihong

    2004-12-01

    protein (UCP-1 mRNA levels in brown adipose tissue (BAT were seen in Phyto-600 fed males. However, decreased core body temperature was recorded in these same animals compared to Phyto-free fed animals. Conclusions This study demonstrates that consumption of a soy-based (isoflavone-rich diet, significantly alters several parameters involved in maintaining body homeostatic balance, energy expenditure, feeding behavior, hormonal, metabolic and neuroendocrine function in male rats.

  19. The cell death factor, cell wall elicitor of rice blast fungus (Magnaporthe grisea) causes metabolic alterations including GABA shunt in rice cultured cells

    Takahashi, Hideyuki; Matsumura, Hideo; Kawai-Yamada, Maki; Uchimiya, Hirofumi

    2008-01-01

    An elicitor derived from the cell wall of rice blast fungus (Magnaporthe grisea) causes cell death in suspension cultured cells of rice (Oryza sativa L.). To elucidate the role of M. grisea elicitor on metabolic pathway of rice cells, we performed metabolite profiling using capillary electrophoresis-mass spectrometry (CE/MS). Treatment with M. grisea elicitor increased the amounts of antioxidants and free amino acids and decreased the amount of metabolites in the tricarboxylic acid (TCA) cycl...

  20. PTENα, a PTEN isoform translated through alternative initiation, regulates mitochondrial function and energy metabolism.

    Liang, Hui; He, Shiming; Yang, Jingyi; Jia, Xinying; Wang, Pan; Chen, Xi; Zhang, Zhong; Zou, Xiajuan; McNutt, Michael A; Shen, Wen Hong; Yin, Yuxin

    2014-05-06

    PTEN is one of the most frequently mutated genes in human cancer. It is known that PTEN has a wide range of biological functions beyond tumor suppression. Here, we report that PTENα, an N-terminally extended form of PTEN, functions in mitochondrial metabolism. Translation of PTENα is initiated from a CUG codon upstream of and in-frame with the coding region of canonical PTEN. Eukaryotic translation initiation factor 2A (eIF2A) controls PTENα translation, which requires a CUG-centered palindromic motif. We show that PTENα induces cytochrome c oxidase activity and ATP production in mitochondria. TALEN-mediated somatic deletion of PTENα impairs mitochondrial respiratory chain function. PTENα interacts with canonical PTEN to increase PINK1 protein levels and promote energy production. Our studies demonstrate the importance of eIF2A-mediated alternative translation for generation of protein diversity in eukaryotic systems and provide insights into the mechanism by which the PTEN family is involved in multiple cellular processes. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Estimated glomerular filtration rate function in patients with and without metabolic syndrome

    María E Lizardo

    2016-06-01

    Full Text Available Introduction: Metabolic syndrome (MS is an independent risk factor, which affects the development of chronic kidney disease, so the glomerular filtration rate (GFR as an indicator of glomerular function in patients with and without MS who attended the outpatient clinic “los Grillitos, sector Caña de Azucar”. Materials and Methods: A comparative, correlational, cross-sectional study was conducted in a non-probability sample of convenience consisting of 60 patients with MS diagnosed according to the criteria Panel ATP III, and 60 apparently healthy individuals, whom the GFR was determined by the Cockcroft-Gault as well as clinical and biochemical parameters for the diagnosis of MS. Results: Out of the total patients evaluated, 37 (30.7% showed alterations that put them in grades G2 and G3 system risk stratification of CKD, of these 18 and 19 corresponded to patients with and without MS respectively. Glomerular Hyperfiltration (> 120 mil / min it was found in both groups 28 (46.7% and 24 (40% cases of patients with and without MS respectively. The glomerular function was strongly correlated with abdominal obesity and high levels of stress arterial. As for the number of criteria and its relationship to the level of kidney damage present, not a firm to increase the latter with respect to the first (p=0.385 trend was observed. Conclusion: The change in the glomerular function is not directly related to the MS but with its components, specifically abdominal obesity and hypertension.

  2. Cognitive functions in middle aged individuals are related to metabolic disturbances and aerobic capacity

    Pedersen, Maria; Pedersen, Karin Kaereby; Bruunsgaard, Helle

    2012-01-01

    Metabolic disturbances may contribute to cognitive dysfunction in patients with type 2 diabetes. We investigated the relation between cognitive impairment and metabolic deteriorations, low physical fitness, low-grade inflammation and abdominal obesity in middle aged individuals.......Metabolic disturbances may contribute to cognitive dysfunction in patients with type 2 diabetes. We investigated the relation between cognitive impairment and metabolic deteriorations, low physical fitness, low-grade inflammation and abdominal obesity in middle aged individuals....

  3. Effect of metabolic alkalosis on respiratory function in patients with chronic obstructive lung disease.

    Bear, R.; Goldstein, M.; Phillipson, E.; Ho, M.; Hammeke, M.; Feldman, R.; Handelsman, S.; Halperin, M.

    1977-01-01

    Eleven instances of a mixed acid-base disorder consisting of chronic respiratory acidosis and metabolic alkalosis were recognized in eight patients with chronic obstructive lung disease and carbon dioxide retention. Correction of the metabolic alkalosis led to substantial improvement in blood gas values and clinical symptoms. Patients with mixed chronic respiratory acidosis and metabolic alkalosis constitute a common subgroup of patients with chronic obstructive lung disease and carbon dioxide retention; these patients benefit from correction of the metabolic alkalosis. PMID:21028

  4. Pseudomonas putida as a functional chassis for industrial biocatalysis: From native biochemistry to trans-metabolism.

    Nikel, Pablo I; de Lorenzo, Víctor

    2018-05-16

    The itinerary followed by Pseudomonas putida from being a soil-dweller and plant colonizer bacterium to become a flexible and engineer-able platform for metabolic engineering stems from its natural lifestyle, which is adapted to harsh environmental conditions and all sorts of physicochemical stresses. Over the years, these properties have been capitalized biotechnologically owing to the expanding wealth of genetic tools designed for deep-editing the P. putida genome. A suite of dedicated vectors inspired in the core tenets of synthetic biology have enabled to suppress many of the naturally-occurring undesirable traits native to this species while enhancing its many appealing properties, and also to import catalytic activities and attributes from other biological systems. Much of the biotechnological interest on P. putida stems from the distinct architecture of its central carbon metabolism. The native biochemistry is naturally geared to generate reductive currency [i.e., NAD(P)H] that makes this bacterium a phenomenal host for redox-intensive reactions. In some cases, genetic editing of the indigenous biochemical network of P. putida (cis-metabolism) has sufficed to obtain target compounds of industrial interest. Yet, the main value and promise of this species (in particular, strain KT2440) resides not only in its capacity to host heterologous pathways from other microorganisms, but also altogether artificial routes (trans-metabolism) for making complex, new-to-Nature molecules. A number of examples are presented for substantiating the worth of P. putida as one of the favorite workhorses for sustainable manufacturing of fine and bulk chemicals in the current times of the 4th Industrial Revolution. The potential of P. putida to extend its rich native biochemistry beyond existing boundaries is discussed and research bottlenecks to this end are also identified. These aspects include not just the innovative genetic design of new strains but also the incorporation of

  5. CHANGING METABOLIC FUNCTIONS IN EXPERIMENTAL ANIMALS AFTER INTRODUCTION OF THE XENOBIOTIC, IMMUNOTROPIC DRUG AND PROBIOTIC

    Zvyagintseva O.V.

    2015-05-01

    Full Text Available The aim of the study was to evaluate in vivo changes in metabolic and barrier function of the resistance factors (activity of enzymes of neutrophils, the efficiency of phagocytosis, some biochemical parameters (concentration of ceruloplasmin and haptoglobin and proliferate activity in vitro cells after introduction of copper sulfate, probiotics and immunostimulant "Fungidol" the experimental animals. Material and methods. The in vivo experiments were performed on 6-month-old male rats of Wistar line. Identified the following groups: group 1 - control animals, which were intraperitoneally injected with saline (n = 5; group 2 - animals that were administered saline per os and 48 hours a solution of copper sulphate intraperitoneally (n = 5; group 3 - animals, which were injected with immunotropic drug "Fungidol" per os and 48 hours a solution of copper sulphate intraperitoneally (n = 5; group 4 animals, which were injected with a solution of probiotics per os and 48 hours a solution of copper sulphate intraperitoneally (n = 5. As a probiotic used capsules firm Yogurt that contains active Lactobacillus acidophilus, Lactobacillus rhamnosus, Streptococcus thermophillus, Lactobacillus bulgaricus. The concentration of haptoglobin and ceruloplasmin were determined spectrophotometrically. Oxygen-dependent metabolism of neutrophils was investigated by microscopy according to their ability to absorb nitroblue tetrazolium (NBT-test and restore it to deformazione in the form of granules blue color under the influence of superoxide anion, which is formed in the NADP-oxidase reaction, initiating the process of stimulation of phagocytosis (NBT-test. To determine the barrier function of phagocytic cells by light microscopy to evaluate the activity of phagocytosis of neutrophilic granulocytes with subsequent determination of phagocytic index, phagocytic number and the index of completeness of phagocytosis. As a microbial agent used is a suspension culture of

  6. Effect of basal ganglia calcification on its glucose metabolism and dopaminergic function in idiopathic hypoparathyroidism.

    Modi, Sagar; Arora, Geetanjali; Bal, Chandra Shekhar; Sreenivas, Vishnubhatla; Kailash, Suparna; Sagar, Rajesh; Goswami, Ravinder

    2015-10-01

    The functional significance of basal ganglia calcification (BGC) in idiopathic hypoparathyroidism (IH) is not clear. To assess the effect of BGC on glucose metabolism and dopaminergic function in IH. (18) F-FDG and (99m) Tc-TRODAT-1 nuclear imaging were performed in 35 IH patients with (n = 26) and without (n = 9) BGC. Controls were subjects without hypoparathyroidism or BGC (nine for (18) F-FDG and 12 for (99m) Tc-TRODAT-1). Relationship of the glucose metabolism and dopaminergic function was assessed with the neuropsychological and biochemical abnormalities. (18) F-FDG uptake in IH patients with calcification at caudate and striatum was less than that of IH patients without calcification (1·06 ± 0·13 vs 1·24 ± 0·09, P = <0·0001 and 1·06 ± 0·09 vs 1·14 ± 0·08, P = 0·03, respectively). (18) F-FDG uptake did not correlate with neuropsychological dysfunctions. (18) F-FDG uptake in IH without BGC was significantly lower than that of controls. The mean (99m) Tc-TRODAT-1 uptake at basal ganglia was comparable between IH with and without BGC and between IH without BGC and controls. Serum calcium-phosphorus ratio maintained by the patients correlated with (18) F-FDG uptake at striatum (r = 0·57, P = 0·001). For every 0·1 unit reduction in calcium-phosphorus ratio, (18) F-FDG uptake decreased by 2·5 ± 0·68% (P = 0·001). BGC was associated with modest reduction (15%) in (18) F-FDG uptake at basal ganglia in IH but did not affect dopaminergic function. (18) F-FDG uptake did not correlate with neuropsychological dysfunctions. Interestingly, chronic hypocalcaemia-hyperphosphataemia also contributed to reduction in (18) F-FDG uptake which was independent of BGC. © 2014 John Wiley & Sons Ltd.

  7. [Effects of nitrogen application rate on faba bean fusarium wilt and rhizospheric microbial metabolic functional diversity].

    Dong, Yan; Yang, Zhi-xian; Dong, Kun; Tang, Li; Zheng, Yi; Hu, Guo-bin

    2013-04-01

    A field plot experiment was conducted to study the effects of different nitrogen (N) application rates on the microbial functional diversity in faba bean rhizosphere and the relationships between the microbial functional diversity and the occurrence of faba bean fusarium wilt. Four nitrogen application rates were installed, i. e. , N0(0 kg hm-2 , N1 (56. 25 kg hm-2) , N2(112. 5 kg hm-2), and N3 (168.75 kg hm-2), and Biolog microbial analysis system was applied to study the damage of faba bean fusarium wilt and the rhizospheric microbial metabolic functional diversity. Applying N (N1 N2, and N3) decreased the disease index of faba bean fusarium wilt and the quantity of Fusarium oxysporum significantly, and increased the quantities of bacteria and actinomyces and the ratios of bacteria/fungi and actinomyces/fungi significantly, with the peak values of bacteria and actinomyces, bacteria/fungi, and actinomyces/fungi, and the lowest disease index and F. oxysporum density in N2. As compared with N0, applying N increased the AWCD value significantly, but the effects of different N application rates on the ability of rhizospheric microbes in utilizing six types of carbon sources had definite differences. Under the application of N, the utilization rates of carbohydrates, carboxylic acids, and amino acids by the rhizospheric microbes were higher. Principal component analysis demonstrated that applying N changed the rhizospheric microbial community composition obviously, and the carbohydrates, carboxylic acids, and amino acids were the sensitive carbon sources differentiating the changes of the microbial community induced by N application. Applying N inhibited the utilization of carbohydrates and carboxylic acids but improved the utilization of amino acids and phenolic acids by the rhizospheric microbes, which could be one of the main reasons of applying N being able to reduce the harm of faba bean fusarium wilt. It was suggested that rationally applying N could increase the

  8. The Role of Muscle Mass, Muscle Quality, and Body Composition in Risk for the Metabolic Syndrome and Functional Decline in Older Adults: Topical Collection on Nutrition, Obesity, and Diabetes

    R.T. Mankowski (Robert T.); S.D. Anton (Stephen D.); M. Aubertin-Leheudre (Mylene)

    2015-01-01

    textabstractAbstract Age-related body composition changes include both loss of muscle mass (sarcopenia) and increase in fat mass, which jointly contribute to a decline in metabolic functions. Muscle quality is positively related to functional capacity and a lower risk for the development of the

  9. The acute effect of coffee on endothelial function and glucose metabolism following a glucose load in healthy human volunteers.

    Boon, Evan A J; Croft, Kevin D; Shinde, Sujata; Hodgson, Jonathan M; Ward, Natalie C

    2017-09-20

    A diet rich in plant polyphenols has been suggested to reduce the incidence of cardiovascular disease and type 2 diabetes mellitus, in part, via improvements in endothelial function. Coffee is a rich source of phenolic compounds including the phenolic acid, chlorogenic acid (CGA). The aim of the study was to investigate the effect of coffee as a whole beverage on endothelial function, blood pressure and blood glucose concentration. Twelve healthy men and women were recruited to a randomised, placebo-controlled, cross-over study, with three treatments tested: (i) 18 g of ground caffeinated coffee containing 300 mg CGA in 200 mL of hot water, (ii) 18 g of decaffeinated coffee containing 287 mg CGA in 200 mL of hot water, and (iii) 200 mL of hot water (control). Treatment beverages were consumed twice, two hours apart, with the second beverage consumed simultaneously with a 75 g glucose load. Blood pressure was recorded and the finger prick glucose test was performed at time = 0 and then every 30 minutes up to 2 hours. Endothelial function, assessed using flow-mediated dilatation (FMD) of the brachial artery, was measured at 1 hour and a blood sample taken at 2 hours to measure plasma nitrate/nitrite and 5-CGA concentrations. The FMD response was significantly higher in the caffeinated coffee group compared to both decaffeinated coffee and water groups (P coffee and water. Blood glucose concentrations and blood pressure were not different between the three treatment groups. In conclusion, the consumption of caffeinated coffee resulted in a significant improvement in endothelial function, but there was no evidence for benefit regarding glucose metabolism or blood pressure. Although the mechanism has yet to be elucidated the results suggest that coffee as a whole beverage may improve endothelial function, or that caffeine is the component of coffee responsible for improving FMD.

  10. Lung function and metabolic syndrome: Findings of National Health and Nutrition Examination Survey 2007–2010*

    FORD, Earl S.; CUNNINGHAM, Timothy J.; MERCADO, Carla I.

    2015-01-01

    Background Considerable uncertainty remains about obstructive lung function (OLF) in adults with metabolic syndrome (MetS). The aim of the present study was to examine pulmonary function status in adults with and without MetS. Methods We used data from 3109 participants aged ≥20 years of the National Health and Nutrition Examination Survey 2007–2010. Subjects’ MetS status was established on the basis of the 2009 harmonizing definition. Participants received spirometry. Results After age adjustment, 79.3% (SE 1.1) of participants with MetS had normal lung function, 8.7% (0.9) had restrictive lung function (RLF), 7.1% (0.8) had mild OLF, and 4.8% (0.6) had moderate OLF or worse. Among participants without MetS, these estimates were 78.7% (1.2), 3.9% (0.6), 10.9% (1.1), and 6.4% (0.8), respectively. After multiple adjustment, participants with MetS were more likely to have RLF (adjusted prevalence ratio [aPR] 2.20; 95% confidence interval [CI] 1.67, 2.90) and less likely to have any OLF (aPR 0.73; 95% CI 0.62, 0.86) than those without MetS. Furthermore, participants with MetS had lower mean levels of forced expiratory volume in one second (FEV1), FEV1 % predicted, forced vital capacity (FVC), and FVC % predicted, but a higher FEV1/FVC ratio than participants without MetS. Mean levels of FEV1, FEV1 % predicted, FVC, and FVC % predicted declined significantly, but not the FEV1/FVC ratio, as the number of components increased. Conclusions Compared with adults without MetS, spirometry is more likely to show a restrictive pattern and less likely to show an obstructive pattern among adults with MetS. PMID:26677470

  11. Scaffold-free 3D bio-printed human liver tissue stably maintains metabolic functions useful for drug discovery.

    Kizawa, Hideki; Nagao, Eri; Shimamura, Mitsuru; Zhang, Guangyuan; Torii, Hitoshi

    2017-07-01

    The liver plays a central role in metabolism. Although many studies have described in vitro liver models for drug discovery, to date, no model has been described that can stably maintain liver function. Here, we used a unique, scaffold-free 3D bio-printing technology to construct a small portion of liver tissue that could stably maintain drug, glucose, and lipid metabolism, in addition to bile acid secretion. This bio-printed normal human liver tissue maintained expression of several kinds of hepatic drug transporters and metabolic enzymes that functioned for several weeks. The bio-printed liver tissue displayed glucose production via cAMP/protein kinase A signaling, which could be suppressed with insulin. Bile acid secretion was also observed from the printed liver tissue, and it accumulated in the culture medium over time. We observed both bile duct and sinusoid-like structures in the bio-printed liver tissue, which suggested that bile acid secretion occurred via a sinusoid-hepatocyte-bile duct route. These results demonstrated that our bio-printed liver tissue was unique, because it exerted diverse liver metabolic functions for several weeks. In future, we expect our bio-printed liver tissue to be applied to developing new models that can be used to improve preclinical predictions of long-term toxicity in humans, generate novel targets for metabolic liver disease, and evaluate biliary excretion in drug development.

  12. Beneficial Autophagic Activities, Mitochondrial Function, and Metabolic Phenotype Adaptations Promoted by High-Intensity Interval Training in a Rat Model

    Fang-Hui Li

    2018-05-01

    Full Text Available The effects of high-intensity interval (HIIT and moderate-intensity continuous training (MICT on basal autophagy and mitochondrial function in cardiac and skeletal muscle and plasma metabolic phenotypes have not been clearly characterized. Here, we investigated how 10-weeks HIIT and MICT differentially modify basal autophagy and mitochondrial markers in cardiac and skeletal muscle and conducted an untargeted metabolomics study with proton nuclear magnetic resonance (1H NMR spectroscopy and multivariate statistical analysis of plasma metabolic phenotypes. Male Sprague–Dawley rats were separated into three groups: sedentary control (SED, MICT, and HIIT. Rats underwent evaluation of exercise performance, including exercise tolerance and grip strength, and blood lactate levels were measured immediately after an incremental exercise test. Plasma samples were analyzed by 1H NMR. The expression of autophagy and mitochondrial markers and autophagic flux (LC3II/LC3-I ratio in cardiac, rectus femoris, and soleus muscle were analyzed by western blotting. Time to exhaustion and grip strength increased significantly following HIIT compared with that in both SED and MICT groups. Compared with those in the SED group, blood lactate level, and the expression of SDH, COX-IV, and SIRT3 significantly increased in rectus femoris and soleus muscle of both HIIT and MICT groups. Meanwhile, SDH and COX-IV content of cardiac muscle and COX-IV and SIRT3 content of rectus femoris and soleus muscle increased significantly following HIIT compared with that following MICT. The expression of LC3-II, ATG-3, and Beclin-1 and LC3II/LC3-I ratio were significantly increased only in soleus and cardiac muscle following HIIT. These data indicate that HIIT was more effective for improving physical performance and facilitating cardiac and skeletal muscle adaptations that increase mitochondrial function and basal autophagic activities. Moreover, 1H NMR spectroscopy and multivariate

  13. Beneficial Autophagic Activities, Mitochondrial Function, and Metabolic Phenotype Adaptations Promoted by High-Intensity Interval Training in a Rat Model.

    Li, Fang-Hui; Li, Tao; Ai, Jing-Yi; Sun, Lei; Min, Zhu; Duan, Rui; Zhu, Ling; Liu, Yan-Ying; Liu, Timon Cheng-Yi

    2018-01-01

    The effects of high-intensity interval (HIIT) and moderate-intensity continuous training (MICT) on basal autophagy and mitochondrial function in cardiac and skeletal muscle and plasma metabolic phenotypes have not been clearly characterized. Here, we investigated how 10-weeks HIIT and MICT differentially modify basal autophagy and mitochondrial markers in cardiac and skeletal muscle and conducted an untargeted metabolomics study with proton nuclear magnetic resonance ( 1 H NMR) spectroscopy and multivariate statistical analysis of plasma metabolic phenotypes. Male Sprague-Dawley rats were separated into three groups: sedentary control (SED), MICT, and HIIT. Rats underwent evaluation of exercise performance, including exercise tolerance and grip strength, and blood lactate levels were measured immediately after an incremental exercise test. Plasma samples were analyzed by 1 H NMR. The expression of autophagy and mitochondrial markers and autophagic flux (LC3II/LC3-I ratio) in cardiac, rectus femoris, and soleus muscle were analyzed by western blotting. Time to exhaustion and grip strength increased significantly following HIIT compared with that in both SED and MICT groups. Compared with those in the SED group, blood lactate level, and the expression of SDH, COX-IV, and SIRT3 significantly increased in rectus femoris and soleus muscle of both HIIT and MICT groups. Meanwhile, SDH and COX-IV content of cardiac muscle and COX-IV and SIRT3 content of rectus femoris and soleus muscle increased significantly following HIIT compared with that following MICT. The expression of LC3-II, ATG-3, and Beclin-1 and LC3II/LC3-I ratio were significantly increased only in soleus and cardiac muscle following HIIT. These data indicate that HIIT was more effective for improving physical performance and facilitating cardiac and skeletal muscle adaptations that increase mitochondrial function and basal autophagic activities. Moreover, 1 H NMR spectroscopy and multivariate statistical

  14. Functional genomics tools applied to plant metabolism: a survey on plant respiration, its connections and the annotation of complex gene functions

    Wagner L. Araújo

    2012-09-01

    Full Text Available The application of post-genomic techniques in plant respiration studies has greatly improved our ability to assign functions to gene products. In addition it has also revealed previously unappreciated interactions between distal elements of metabolism. Such results have reinforced the need to consider plant respiratory metabolism as part of a complex network and making sense of such interactions will ultimately require the construction of predictive and mechanistic models. Transcriptomics, proteomics, metabolomics and the quantification of metabolic flux will be of great value in creating such models both by facilitating the annotation of complex gene function, determining their structure and by furnishing the quantitative data required to test them. In this review we highlight how these experimental approaches have contributed to our current understanding of plant respiratory metabolism and its interplay with associated process (e.g. photosynthesis, photorespiration and nitrogen metabolism. We also discuss how data from these techniques may be integrated, with the ultimate aim of identifying mechanisms that control and regulate plant respiration and discovering novel gene functions with potential biotechnological implications.

  15. Overfeeding Dairy Cattle During Late-Pregnancy Alters Hepatic PPARα-Regulated Pathways Including Hepatokines: Impact on Metabolism and Peripheral Insulin Sensitivity

    Khan, M Jawad; Jacometo, Carolina B; Graugnard, Daniel E; Corrêa, Marcio N; Schmitt, Eduardo; Cardoso, Felipe; Loor, Juan J

    2014-01-01

    Hepatic metabolic gene networks were studied in dairy cattle fed control (CON, 1.34 Mcal/kg) or higher energy (overfed (OVE), 1.62 Mcal/kg) diets during the last 45 days of pregnancy. A total of 57 target genes encompassing PPARα-targets/co-regulators, hepatokines, growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis, lipogenesis, and lipoprotein metabolism were evaluated on −14, 7, 14, and 30 days around parturition. OVE versus CON cows were in more negative energy balance (NEB) postpartum and had greater serum non-esterified fatty acids (NEFA), β-hydroxybutyrate (BHBA), and liver triacylglycerol (TAG) concentrations. Milk synthesis rate did not differ. Liver from OVE cows responded to postpartal NEB by up-regulating expression of PPARα-targets in the fatty acid oxidation and ketogenesis pathways, along with gluconeogenic genes. Hepatokines (fibroblast growth factor 21 (FGF21), angiopoietin-like 4 (ANGPTL4)) and apolipoprotein A-V (APOA5) were up-regulated postpartum to a greater extent in OVE than CON. OVE led to greater blood insulin prepartum, lower NEFA:insulin, and greater lipogenic gene expression suggesting insulin sensitivity was not impaired. A lack of change in APOB, MTTP, and PNPLA3 coupled with upregulation of PLIN2 postpartum in cows fed OVE contributed to TAG accumulation. Postpartal responses in NEFA and FGF21 with OVE support a role of this hepatokine in diminishing adipose insulin sensitivity. PMID:24737933

  16. Effect of the Aged Garlic Extract on Cardiovascular Function in Metabolic Syndrome Rats

    Israel Pérez-Torres

    2016-10-01

    Full Text Available The antioxidant properties of aged garlic extract (AGE on cardiovascular functioning (CF in metabolic syndrome (MS remains poorly studied. Here we study the AGE effects on CF in a rat model of MS. Control rats plus saline solution (C + SS, MS rats (30% sucrose in drinking water from weaning plus saline solution (MS + SS, control rats receiving AGE (C + AGE 125 mg/Kg/12 h and MS rats with AGE (MS + AGE were studied. MS + SS had increased triglycerides, systolic blood pressure, insulin, leptin, HOMA index, and advanced glycation end products. AGE returned their levels to control values (p < 0.01. Cholesterol was decreased by AGE (p = 0.05. Glutathion and GPx activity were reduced in MS + SS rats and increased with AGE (p = 0.05. Lipid peroxidation was increased in MS + SS and AGE reduced it (p = 0.001. Vascular functioning was deteriorated by MS (increased vasocontraction and reduced vasodilation and AGE improved it (p = 0.001. Coronary vascular resistance was increased in MS rats and AGE decreased it (p = 0.001. Cardiac performance was not modified by MS but AGE increased it. NO measured in the perfusate liquid from the heart and serum citrulline, nitrites/nitrates were decreased in MS and AGE increased them (p < 0.01. In conclusion, AGE reduces MS-induced cardiovascular risk, through its anti-oxidant properties.

  17. Aldehyde Dehydrogenases in Arabidopsis thaliana: Biochemical Requirements, Metabolic Pathways, and Functional Analysis.

    Stiti, Naim; Missihoun, Tagnon D; Kotchoni, Simeon O; Kirch, Hans-Hubert; Bartels, Dorothea

    2011-01-01

    Aldehyde dehydrogenases (ALDHs) are a family of enzymes which catalyze the oxidation of reactive aldehydes to their corresponding carboxylic acids. Here we summarize molecular genetic and biochemical analyses of selected ArabidopsisALDH genes. Aldehyde molecules are very reactive and are involved in many metabolic processes but when they accumulate in excess they become toxic. Thus activity of aldehyde dehydrogenases is important in regulating the homeostasis of aldehydes. Overexpression of some ALDH genes demonstrated an improved abiotic stress tolerance. Despite the fact that several reports are available describing a role for specific ALDHs, their precise physiological roles are often still unclear. Therefore a number of genetic and biochemical tools have been generated to address the function with an emphasis on stress-related ALDHs. ALDHs exert their functions in different cellular compartments and often in a developmental and tissue specific manner. To investigate substrate specificity, catalytic efficiencies have been determined using a range of substrates varying in carbon chain length and degree of carbon oxidation. Mutational approaches identified amino acid residues critical for coenzyme usage and enzyme activities.

  18. Improvement of mitochondrial function and dynamics by the metabolic enhancer piracetam.

    Stockburger, Carola; Kurz, Christopher; Koch, Konrad A; Eckert, Schamim H; Leuner, Kristina; Müller, Walter E

    2013-10-01

    The metabolic enhancer piracetam is used in many countries to treat cognitive impairment in aging, brain injuries, as well as dementia such as AD (Alzheimer's disease). As a specific feature of piracetam, beneficial effects are usually associated with mitochondrial dysfunction. In previous studies we were able to show that piracetam enhanced ATP production, mitochondrial membrane potential as well as neurite outgrowth in cell and animal models for aging and AD. To investigate further the effects of piracetam on mitochondrial function, especially mitochondrial fission and fusion events, we decided to assess mitochondrial morphology. Human neuroblastoma cells were treated with the drug under normal conditions and under conditions imitating aging and the occurrence of ROS (reactive oxygen species) as well as in stably transfected cells with the human wild-type APP (amyloid precursor protein) gene. This AD model is characterized by expressing only 2-fold more human Aβ (amyloid β-peptide) compared with control cells and therefore representing very early stages of AD when Aβ levels gradually increase over decades. Interestingly, these cells exhibit an impaired mitochondrial function and morphology under baseline conditions. Piracetam is able to restore this impairment and shifts mitochondrial morphology back to elongated forms, whereas there is no effect in control cells. After addition of a complex I inhibitor, mitochondrial morphology is distinctly shifted to punctate forms in both cell lines. Under these conditions piracetam is able to ameliorate morphology in cells suffering from the mild Aβ load, as well as mitochondrial dynamics in control cells.

  19. Protein O-linked ß-N-acetylglucosamine: A novel effector of cardiomyocyte metabolism and function

    Darley-Usmar, Victor M.; Ball, Lauren E.; Chatham, John C.

    2014-01-01

    The post-translational modification of serine and threonine residues of nuclear and cytoplasmic proteins by the O-linked attachment of the monosaccharide ß-N-acetyl-glucosamine (O-GlcNAc) is emerging as an important mechanism for the regulation of numerous biological processes critical for normal cell function. Active synthesis of O-GlcNAc is essential for cell viability and acute activation of pathways resulting in increased protein O-GlcNAc levels improves the tolerance of cells to a wide range of stress stimuli. Conversely sustained increases in O-GlcNAc levels have been implicated in numerous chronic disease states, especially as a pathogenic contributor to diabetic complications. There has been increasing interest in the role of O-GlcNAc in the heart and vascular system and acute activation of O-GlcNAc levels have been shown to reduce ischemia/reperfusion injury attenuate vascular injury responses as well mediate some of the detrimental effects of diabetes and hypertension on cardiac and vascular function. Here we provide an overview of our current understanding of pathways regulating protein O-GlcNAcylation, summarize the different methodologies for identifying and characterizing O-GlcNAcylated proteins and subsequently focus on two emerging areas: 1) the role of O-GlcNAc as a potential regulator of cardiac metabolism and 2) the cross talk between O-GlcNAc and reactive oxygen species. PMID:21878340

  20. Resting metabolic rate, pulmonary functions, and body composition parameters in children with attention deficit hyperactivity disorder.

    Alpaslan, Ahmet Hamdi; Ucok, Kagan; Coşkun, Kerem Şenol; Genc, Abdurrahman; Karabacak, Hatice; Guzel, Halil Ibrahim

    2017-03-01

    Several studies of school-aged children with attention deficit hyperactivity disorder (ADHD) have found a higher prevalence of overweight/obesity compared with the general population. However, the scientific literature contains insufficient evidence to establish clear conclusions on pulmonary functions, resting metabolic rate (RMR), and body composition in children with ADHD. This study therefore investigates the pulmonary functions tests (PFTs), RMR, and body composition parameters in children with ADHD and evaluates their quality of life. Forty children with ADHD and 40 healthy controls participated in the study. The children's parents completed Conners' parent rating scale (CPRS) and the pediatric quality of life (PedsQL), and their teachers completed Conners' Teacher rating scale (CTRS). The child participants also completed the PedsQL. RMR, PFTs, and body composition parameters were investigated. No significant differences in age, gender, and socioeconomic level were found. All CPRS subscales, except anxiety and psychosomatic conditions, were significantly different (p ADHD group. The results showed that the ADHD group's quality of life is worse than the control group. Body mass index, body composition parameters, RMR, and PFTs were not statistically different between the children with ADHD and the healthy controls. Further studies with complex designs are needed to confirm the results.

  1. The effect of androgen excess on maternal metabolism, placental function and fetal growth in obese dams.

    Fornes, Romina; Maliqueo, Manuel; Hu, Min; Hadi, Laila; Jimenez-Andrade, Juan M; Ebefors, Kerstin; Nyström, Jenny; Labrie, Fernand; Jansson, Thomas; Benrick, Anna; Stener-Victorin, Elisabet

    2017-08-14

    Pregnant women with polycystic ovary syndrome (PCOS) are often overweight or obese. To study the effects of maternal androgen excess in obese dams on metabolism, placental function and fetal growth, female C57Bl6J mice were fed a control (CD) or a high fat/high sucrose (HF/HS) diet for 4-10 weeks, and then mated. On gestational day (GD) 15.5-17.5, dams were injected with dihydrotestosterone (CD-DHT, HF/HS-DHT) or a vehicle (CD-Veh, HF/HS-Veh). HF/HS dams had higher fat content, both before mating and on GD18.5, with no difference in glucose homeostasis, whereas the insulin sensitivity was higher in DHT-exposed dams. Compared to the CD groups, the livers from HF/HS dams weighed more on GD18.5, the triglyceride content was higher, and there was a dysregulation of liver enzymes related to lipogenesis and higher mRNA expression of Fitm1. Fetuses from HF/HS-Veh dams had lower liver triglyceride content and mRNA expression of Srebf1c. Maternal DHT exposure, regardless of diet, decreased fetal liver Pparg mRNA expression and increased placental androgen receptor protein expression. Maternal diet-induced obesity, together with androgen excess, affects maternal and fetal liver function as demonstrated by increased triglyceride content and dysfunctional expression of enzymes and transcription factors involved in de novo lipogenesis and fat storage.

  2. Supraoptic oxytocin and vasopressin neurons function as glucose and metabolic sensors

    Song, Zhilin; Levin, Barry E.; Stevens, Wanida

    2014-01-01

    Neurons in the supraoptic nuclei (SON) produce oxytocin and vasopressin and express insulin receptors (InsR) and glucokinase. Since oxytocin is an anorexigenic agent and glucokinase and InsR are hallmarks of cells that function as glucose and/or metabolic sensors, we evaluated the effect of glucose, insulin, and their downstream effector ATP-sensitive potassium (KATP) channels on calcium signaling in SON neurons and on oxytocin and vasopressin release from explants of the rat hypothalamo-neurohypophyseal system. We also evaluated the effect of blocking glucokinase and phosphatidylinositol 3 kinase (PI3K; mediates insulin-induced mobilization of glucose transporter, GLUT4) on responses to glucose and insulin. Glucose and insulin increased intracellular calcium ([Ca2+]i). The responses were glucokinase and PI3K dependent, respectively. Insulin and glucose alone increased vasopressin release (P glucose in the presence of insulin. The oxytocin (OT) and vasopressin (VP) responses to insulin+glucose were blocked by the glucokinase inhibitor alloxan (4 mM; P ≤ 0.002) and the PI3K inhibitor wortmannin (50 nM; OT: P = 0.03; VP: P ≤ 0.002). Inactivating KATP channels with 200 nM glibenclamide increased oxytocin and vasopressin release (OT: P neurons functioning as glucose and “metabolic” sensors to participate in appetite regulation. PMID:24477542

  3. Decreased in vitro mitochondrial function is associated with enhanced brain metabolism, blood flow, and memory in Surf1-deficient mice

    Lin, Ai-Ling; Pulliam, Daniel A; Deepa, Sathyaseelan S; Halloran, Jonathan J; Hussong, Stacy A; Burbank, Raquel R; Bresnen, Andrew; Liu, Yuhong; Podlutskaya, Natalia; Soundararajan, Anuradha; Muir, Eric; Duong, Timothy Q; Bokov, Alex F; Viscomi, Carlo; Zeviani, Massimo; Richardson, Arlan G; Van Remmen, Holly; Fox, Peter T; Galvan, Veronica

    2013-01-01

    Recent studies have challenged the prevailing view that reduced mitochondrial function and increased oxidative stress are correlated with reduced longevity. Mice carrying a homozygous knockout (KO) of the Surf1 gene showed a significant decrease in mitochondrial electron transport chain Complex IV activity, yet displayed increased lifespan and reduced brain damage after excitotoxic insults. In the present study, we examined brain metabolism, brain hemodynamics, and memory of Surf1 KO mice using in vitro measures of mitochondrial function, in vivo neuroimaging, and behavioral testing. We show that decreased respiration and increased generation of hydrogen peroxide in isolated Surf1 KO brain mitochondria are associated with increased brain glucose metabolism, cerebral blood flow, and lactate levels, and with enhanced memory in Surf1 KO mice. These metabolic and functional changes in Surf1 KO brains were accompanied by higher levels of hypoxia-inducible factor 1 alpha, and by increases in the activated form of cyclic AMP response element-binding factor, which is integral to memory formation. These findings suggest that Surf1 deficiency-induced metabolic alterations may have positive effects on brain function. Exploring the relationship between mitochondrial activity, oxidative stress, and brain function will enhance our understanding of cognitive aging and of age-related neurologic disorders. PMID:23838831

  4. Improvement in cardiac function and free fatty acid metabolism in a case of dilated cardiomyopathy with CD36 deficiency.

    Hirooka, K; Yasumura, Y; Ishida, Y; Komamura, K; Hanatani, A; Nakatani, S; Yamagishi, M; Miyatake, K

    2000-09-01

    A 27-year-old man diagnosed as having dilated cardiomyopathy (DCM) without myocardial accumulation of 123I-beta-methyl-iodophenylpentadecanoic acid, and he was found to have type I CD36 deficiency. This abnormality of cardiac free fatty acid metabolism was also confirmed by other methods: 18F-fluoro-2-deoxyglucose positron emission tomography, measurements of myocardial respiratory quotient and cardiac fatty acid uptake. Although the type I CD36 deficiency was reconfirmed after 3 months, the abnormal free fatty acid metabolism improved after carvedilol therapy and was accompanied by improved cardiac function. Apart from a cause-and-effect relationship, carvedilol can improve cardiac function and increase free fatty acid metabolism in patients with both DCM and CD36 deficiency.

  5. Abnormality of cerebral cortical glucose metabolism in temporal lobe epilepsy with cognitive function impairment

    Bang-Hung Yang; Tsung-Szu Yeh; Tung-Ping Su; Jyh-Cheng Chen; Ren-Shyan Liu

    2004-01-01

    Objective: People with epilepsy commonly report having problems with their memory. Many indicate that memory difficulties significantly hinder their functioning at work, in school, and at home. Besides, some studies have reported that memory performance as a prognostic factor is of most value in patients with risk of refractory epilepsy and when used in a multidisciplinary setting. However, the cerebral cortical areas involving memory impairment in epilepsy is still unknown. The purpose of this study was to access changes of cerebral glucose metabolism of epilepsy patients using [F-18] fluorodeoxyglucose positron emission tomography (FDG PET). Method: Nine temporal lobe epilepsy patients were studied. Each patient was confirmed with lesions in right mesial temporal lobe by MRI, PET and EEG. Serial cognition function tests were performed. Regional cerebral glucose metabolism (rCMRglc) was measured by PET at 45 minutes after injection of 370 MBq of FDG. Parametric images were generated by grand mean scaling each scan to 50. The images were then transformed into standard stereotactic space. Statistical parametric mapping (SPM2) was applied to find the correlations between verbal memory, figure memory, perception intelligent quotation (PIQ) and rCMRglc in epilepsy patients. The changes of rCMRglc were significant if corrected p value was less than 0.05. Results: There was no significant relationship between figure memory score and verbal memory score. FDG-PET scan showed changes of rCMRglc positive related with verbal memory score in precentral gyms of right frontal lobe (Brodmann area 4, corrected p < 0.001, voxel size 240) and cingulated gyms of right limbic lobe (Brodmann area 32, corrected p=0.002, voxel size 143). No negative relationship was demonstrable between verbal memory and rCMRglc in this study. Besides, significanfiy positive correlation between figure memory was shown in cuneus of right occipital lobe (Brodmann area 18, corrected p < 0.001, voxel size

  6. The effects of various sources of dietary fibre on cholesterol metabolism and colonic function in healthy subjects

    Stasse-Wolthuis, M.

    1980-01-01

    This thesis deals with the influence of several types of dietary fibre on cholesterol metabolism and colonic function in young healthy subjects. Dietary fibre has been defined as those plant polysaccharides (cellulose, hemicelluloses, pectic substances) and lignin which are resistant to hydrolysis

  7. Tumor microenvironment and metabolic synergy in breast cancers: critical importance of mitochondrial fuels and function.

    Martinez-Outschoorn, Ubaldo; Sotgia, Federica; Lisanti, Michael P

    2014-04-01

    Metabolic synergy or metabolic coupling between glycolytic stromal cells (Warburg effect) and oxidative cancer cells occurs in human breast cancers and promotes tumor growth. The Warburg effect or aerobic glycolysis is the catabolism of glucose to lactate to obtain adenosine triphosphate (ATP). This review summarizes the main findings on this stromal metabolic phenotype, and the associated signaling pathways, as well as the critical role of oxidative stress and autophagy, all of which promote carcinoma cell mitochondrial metabolism and tumor growth. Loss of Caveolin 1 (Cav-1) and the upregulation of monocarboxylate transporter 4 (MCT4) in stromal cells are novel markers of the Warburg effect and metabolic synergy between stromal and carcinoma cells. MCT4 and Cav-1 are also breast cancer prognostic biomarkers. Reactive oxygen species (ROS) are key mediators of the stromal Warburg effect. High ROS also favors cancer cell mitochondrial metabolism and tumorigenesis, and anti-oxidants can reverse this altered stromal and carcinoma metabolism. A pseudo-hypoxic state with glycolysis and low mitochondrial metabolism in the absence of hypoxia is a common feature in breast cancer. High ROS induces loss of Cav-1 in stromal cells and is sufficient to generate a pseudo-hypoxic state. Loss of Cav-1 in the stroma drives glycolysis and lactate extrusion via HIF-1α stabilization and the upregulation of MCT4. Stromal cells with loss of Cav-1 and/or high expression of MCT4 also show a catabolic phenotype, with enhanced macroautophagy. This catabolic state in stromal cells is driven by hypoxia-inducible factor (HIF)-1α, nuclear factor κB (NFκB), and JNK activation and high ROS generation. A feed-forward loop in stromal cells regulates pseudo-hypoxia and metabolic synergy, with Cav-1, MCT4, HIF-1α, NFκB, and ROS as its key elements. Metabolic synergy also may occur between cancer cells and cells in distant organs from the tumor. Cancer cachexia, which is due to severe organismal

  8. Detecting variants with Metabolic Design, a new software tool to design probes for explorative functional DNA microarray development

    Gravelat Fabrice

    2010-09-01

    Full Text Available Abstract Background Microorganisms display vast diversity, and each one has its own set of genes, cell components and metabolic reactions. To assess their huge unexploited metabolic potential in different ecosystems, we need high throughput tools, such as functional microarrays, that allow the simultaneous analysis of thousands of genes. However, most classical functional microarrays use specific probes that monitor only known sequences, and so fail to cover the full microbial gene diversity present in complex environments. We have thus developed an algorithm, implemented in the user-friendly program Metabolic Design, to design efficient explorative probes. Results First we have validated our approach by studying eight enzymes involved in the degradation of polycyclic aromatic hydrocarbons from the model strain Sphingomonas paucimobilis sp. EPA505 using a designed microarray of 8,048 probes. As expected, microarray assays identified the targeted set of genes induced during biodegradation kinetics experiments with various pollutants. We have then confirmed the identity of these new genes by sequencing, and corroborated the quantitative discrimination of our microarray by quantitative real-time PCR. Finally, we have assessed metabolic capacities of microbial communities in soil contaminated with aromatic hydrocarbons. Results show that our probe design (sensitivity and explorative quality can be used to study a complex environment efficiently. Conclusions We successfully use our microarray to detect gene expression encoding enzymes involved in polycyclic aromatic hydrocarbon degradation for the model strain. In addition, DNA microarray experiments performed on soil polluted by organic pollutants without prior sequence assumptions demonstrate high specificity and sensitivity for gene detection. Metabolic Design is thus a powerful, efficient tool that can be used to design explorative probes and monitor metabolic pathways in complex environments

  9. Exploiting immune cell metabolic machinery for functional HIV cure and the prevention of inflammaging [version 1; referees: 4 approved

    Clovis S. Palmer

    2018-01-01

    Full Text Available An emerging paradigm in immunology suggests that metabolic reprogramming and immune cell activation and functions are intricately linked. Viral infections, such as HIV infection, as well as cancer force immune cells to undergo major metabolic challenges. Cells must divert energy resources in order to mount an effective immune response. However, the fact that immune cells adopt specific metabolic programs to provide host defense against intracellular pathogens and how this metabolic shift impacts immune cell functions and the natural course of diseases have only recently been appreciated. A clearer insight into how these processes are inter-related will affect our understanding of several fundamental aspects of HIV persistence. Even in patients with long-term use of anti-retroviral therapies, HIV infection persists and continues to cause chronic immune activation and inflammation, ongoing and cumulative damage to multiple organs systems, and a reduction in life expectancy. HIV-associated fundamental changes to the metabolic machinery of the immune system can promote a state of “inflammaging”, a chronic, low-grade inflammation with specific immune changes that characterize aging, and can also contribute to the persistence of HIV in its reservoirs. In this commentary, we will bring into focus evolving concepts on how HIV modulates the metabolic machinery of immune cells in order to persist in reservoirs and how metabolic reprogramming facilitates a chronic state of inflammation that underlies the development of age-related comorbidities. We will discuss how immunometabolism is facilitating the changing paradigms in HIV cure research and outline the novel therapeutic opportunities for preventing inflammaging and premature development of age-related conditions in HIV+ individuals.

  10. Effect of Graded Unilateral Sanding Exercise on Metabolic and Cardiopulmonary Function in the Healthy and the Hemiparetic Elderly Subjects

    Muraki, Toshiaki

    1997-01-01

    The purpose of this study was to investigate how 18 elderly subjects with cerebral vascular accident (CVA) (14 men and 4 women) and 19 healthy elderly subjects (6 men and 13 women) would respond to a five-step graded unilateral sanding activity. Three indicators of pulmonary function such as expiratory tidal volume, respiratory rate, and expiratory volume and four indicators of cardiometabolic function such as metabolic equivalents (METS), systolic blood pressure, heart rate, and pressure rat...

  11. Effects of Dietary Flavonoids on Reverse Cholesterol Transport, HDL Metabolism, and HDL Function.

    Millar, Courtney L; Duclos, Quinn; Blesso, Christopher N

    2017-03-01

    Strong experimental evidence confirms that HDL directly alleviates atherosclerosis. HDL particles display diverse atheroprotective functions in reverse cholesterol transport (RCT), antioxidant, anti-inflammatory, and antiapoptotic processes. In certain inflammatory disease states, however, HDL particles may become dysfunctional and proatherogenic. Flavonoids show the potential to improve HDL function through their well-documented effects on cellular antioxidant status and inflammation. The aim of this review is to summarize the basic science and clinical research examining the effects of dietary flavonoids on RCT and HDL function. Based on preclinical studies that used cell culture and rodent models, it appears that many flavonoids (e.g., anthocyanidins, flavonols, and flavone subclasses) influence RCT and HDL function beyond simple HDL cholesterol concentration by regulating cellular cholesterol efflux from macrophages and hepatic paraoxonase 1 expression and activity. In clinical studies, dietary anthocyanin intake is associated with beneficial changes in serum biomarkers related to HDL function in a variety of human populations (e.g., in those who are hyperlipidemic, hypertensive, or diabetic), including increased HDL cholesterol concentration, as well as HDL antioxidant and cholesterol efflux capacities. However, clinical research on HDL functionality is lacking for some flavonoid subclasses (e.g., flavanols, flavones, flavanones, and isoflavones). Although there has been a tremendous effort to develop HDL-targeted drug therapies, more research is warranted on how the intake of foods or specific nutrients affects HDL function. © 2017 American Society for Nutrition.

  12. Exosomes and Metabolic Function in Mice Exposed to Alternating Dark-Light Cycles Mimicking Night Shift Work Schedules

    Abdelnaby Khalyfa

    2017-11-01

    Full Text Available Sleep is an important modulator of metabolic function. Disruptions of sleep in circadian rhythm are common in modern societies and are associated with increased risk of developing cardiometabolic disorders. Exosomes are ubiquitous extracellular vesicles that may play a mechanistic role in metabolic derangements. We hypothesized that alternating dark-light cycles mimicking shift work in mice would alter fecal microbiota and colonic epithelium permeability and alter plasma exosome cargo and metabolic function. C57BL/6 mice were randomly assigned to (i control day light (CL, or (ii inverted dark-light every 2 weeks for 8 weeks (IN. Body weight, fat mass and HOMA-IR were measured, along with Tregs, metabolic, and resident macrophages in visceral white adipose tissue (vWAT. Fecal water samples were incubated with confluent colonic epithelium cell cultures in electric cell-substrate impedance sensing (ECIS arrays, and plasma exosomes were added to differentiated adipocytes and insulin-induced pAKT/AKT expression changes were assessed by western blots. Mice exposed to IN showed elevated HOMA-IR, and their fecal samples showed altered microbiota which promote increased permeability of the colonic epithelial cell barrier. Plasma exosomes decreased pAKT/AKT responses to exogenous insulin compared to CL, and altered expression of circadian clock genes. Inflammatory macrophages (Ly-6chigh were increased in IN-exposed vWAT, while Tregs were decreased. Thus, gut microbiota and the cargo of plasma exosomes are altered by periodic shifts in environmental lighting, and effectively alter metabolic function, possibly via induction of systemic inflammation and altered clock expression in target tissues. Further exploration of exosomal miRNA signatures in shift workers and their putative metabolic organ cell targets appears warranted.

  13. SVD identifies transcript length distribution functions from DNA microarray data and reveals evolutionary forces globally affecting GBM metabolism.

    Nicolas M Bertagnolli

    Full Text Available To search for evolutionary forces that might act upon transcript length, we use the singular value decomposition (SVD to identify the length distribution functions of sets and subsets of human and yeast transcripts from profiles of mRNA abundance levels across gel electrophoresis migration distances that were previously measured by DNA microarrays. We show that the SVD identifies the transcript length distribution functions as "asymmetric generalized coherent states" from the DNA microarray data and with no a-priori assumptions. Comparing subsets of human and yeast transcripts of the same gene ontology annotations, we find that in both disparate eukaryotes, transcripts involved in protein synthesis or mitochondrial metabolism are significantly shorter than typical, and in particular, significantly shorter than those involved in glucose metabolism. Comparing the subsets of human transcripts that are overexpressed in glioblastoma multiforme (GBM or normal brain tissue samples from The Cancer Genome Atlas, we find that GBM maintains normal brain overexpression of significantly short transcripts, enriched in transcripts that are involved in protein synthesis or mitochondrial metabolism, but suppresses normal overexpression of significantly longer transcripts, enriched in transcripts that are involved in glucose metabolism and brain activity. These global relations among transcript length, cellular metabolism and tumor development suggest a previously unrecognized physical mode for tumor and normal cells to differentially regulate metabolism in a transcript length-dependent manner. The identified distribution functions support a previous hypothesis from mathematical modeling of evolutionary forces that act upon transcript length in the manner of the restoring force of the harmonic oscillator.

  14. Crosstalk between inflammation, iron metabolism and endothelial function in Behçet's disease.

    Oliveira, Rita; Napoleão, Patricia; Banha, João; Paixão, Eleonora; Bettencourt, Andreia; da Silva, Berta Martins; Pereira, Dina; Barcelos, Filipe; Teixeira, Ana; Patto, José Vaz; Viegas-Crespo, Ana Maria; Costa, Luciana

    2014-01-01

    Behçet's disease (BD) is a rare chronic vasculitis of unclear etiology. It has been suggested that inflammatory response has an important role in BD pathophysiology. Herein, we aimed to study the interplay between inflammation, iron metabolism and endothelial function in BD and search for its putative association with disease activity. Twenty five patients clinically diagnosed with BD were selected and twenty four healthy age-sex matched individuals participated as controls. Results showed an increase of total number of circulating white blood cells and neutrophils, serum transferrin, total iron binding capacity, mieloperoxidase (MPO), ceruloplasmin (Cp), C reactive protein, β2 microglobulin and Cp surface expression in peripheral blood monocytes in BD patients comparatively to healthy individuals (p < 0,05). Of notice, the alterations observed were associated to disease activity status. No significant differences between the two groups were found in serum nitric oxide concentration. The results obtained suggest an important contribution from innate immunity in the pathogenesis of this disease. In particular, surface expression of leukocyte-derived Cp may constitute a new and relevant biomarker to understand BD etiology.

  15. Jatropha curcas, a biofuel crop: functional genomics for understanding metabolic pathways and genetic improvement.

    Maghuly, Fatemeh; Laimer, Margit

    2013-10-01

    Jatropha curcas is currently attracting much attention as an oilseed crop for biofuel, as Jatropha can grow under climate and soil conditions that are unsuitable for food production. However, little is known about Jatropha, and there are a number of challenges to be overcome. In fact, Jatropha has not really been domesticated; most of the Jatropha accessions are toxic, which renders the seedcake unsuitable for use as animal feed. The seeds of Jatropha contain high levels of polyunsaturated fatty acids, which negatively impact the biofuel quality. Fruiting of Jatropha is fairly continuous, thus increasing costs of harvesting. Therefore, before starting any improvement program using conventional or molecular breeding techniques, understanding gene function and the genome scale of Jatropha are prerequisites. This review presents currently available and relevant information on the latest technologies (genomics, transcriptomics, proteomics and metabolomics) to decipher important metabolic pathways within Jatropha, such as oil and toxin synthesis. Further, it discusses future directions for biotechnological approaches in Jatropha breeding and improvement. © 2013 The Authors. Biotechnology Journal published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Functional and structural characterization of a β-glucosidase involved in saponin metabolism from intestinal bacteria.

    Yan, Shan; Wei, Peng-Cheng; Chen, Qiao; Chen, Xin; Wang, Shi-Cheng; Li, Jia-Ru; Gao, Chuan

    2018-02-19

    Saponins are natural glycosides widely used in medicine and the food industry. Although saponin metabolism in human is dependent on intestinal microbes, few involving bacteria enzymes have been identified. We cloned BlBG3, a GH3 β-glucosidase from Bifidobacterium longum, from human stool. We found that BlBG3 catalyzes the hydrolysis of glycoside furostanol and ginsenoside Rb1 at higher efficiency than other microbial β-glucosidases. Structural analysis of BlBG3 in complex with d-glucose revealed its three unique loops, which form a deep pocket and participate in substrate binding. To understand how substrate is bound to the pocket, molecular docking was performed and the binding interactions of protobioside with BlBG3 were revealed. Mutational study suggested that R484 and H642 are critical for enzymatic activity. Our study presents the first structural and functional analysis of a saponin-processing enzyme from human microbiota. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Influence of revascularization on myocardial perfusion, metabolism and function evaluated with I-123-IPPA

    Kropp, J.; Krois, M.; Eichhorn, B.; Feske, W.; Likungu, J.; Kirchhoff, P.J.; Luederitz, B.; Biersack, H.J.; Knapp, F.F. Jr.

    1993-01-01

    Patients with coronary artery disease (CAD) were investigated with sequential SPECT-scintigraphy after administration of 200 MBq of 15-(p-[I-123]iodophenyl)pentadecanoic acid (IPPA) at peak submaximal exercise. Twenty patients underwent coronary angioplasty (PTCA) from which 14 had control coronary arteriography (CA) and left ventricular cineventriculography (LVCV). Nineteen pts underwent bypass graft surgery (ACB) and stress sonagraphy. Semi-quantification of uptake (Up related to perfusion) and turnover (Tr) was obtained by segmental comparison of oblique slices. About 90% of the reperfused myocardial segments in the PTCA-group and 76% in the ACB-group showed an improvement of uptake after therapy (RUp). Of these, 50% and 66% exhibited increased turnover (RTr) after PTCA or ACB. Pathologic RTr was highly correlated with regional wall motion abnormalities after therapy in both groups. In the ACB-group presence of improvement of RTr was correlated with improved RWM at rest and stress. IPPA-studies show potential to provide information about changes of perfusion and metabolism after reperfusion and IPPA-turnover is a good predictor of the pattern of contractile function

  18. Proteome profiling of flax (Linum usitatissimum) seed: characterization of functional metabolic pathways operating during seed development.

    Barvkar, Vitthal T; Pardeshi, Varsha C; Kale, Sandip M; Kadoo, Narendra Y; Giri, Ashok P; Gupta, Vidya S

    2012-12-07

    Flax (Linum usitatissimum L.) seeds are an important source of food and feed due to the presence of various health promoting compounds, making it a nutritionally and economically important plant. An in-depth analysis of the proteome of developing flax seed is expected to provide significant information with respect to the regulation and accumulation of such storage compounds. Therefore, a proteomic analysis of seven seed developmental stages (4, 8, 12, 16, 22, 30, and 48 days after anthesis) in a flax variety, NL-97 was carried out using a combination of 1D-SDS-PAGE and LC-MSE methods. A total 1716 proteins were identified and their functional annotation revealed that a majority of them were involved in primary metabolism, protein destination, storage and energy. Three carbon assimilatory pathways appeared to operate in flax seeds. Reverse transcription quantitative PCR of selected 19 genes was carried out to understand their roles during seed development. Besides storage proteins, methionine synthase, RuBisCO and S-adenosylmethionine synthetase were highly expressed transcripts, highlighting their importance in flax seed development. Further, the identified proteins were mapped onto developmental seed specific expressed sequence tag (EST) libraries of flax to obtain transcriptional evidence and 81% of them had detectable expression at the mRNA level. This study provides new insights into the complex seed developmental processes operating in flax.

  19. PCSK9 at the crossroad of cholesterol metabolism and immune function during infections.

    Paciullo, Francesco; Fallarino, Francesca; Bianconi, Vanessa; Mannarino, Massimo R; Sahebkar, Amirhossein; Pirro, Matteo

    2017-09-01

    Sepsis, a complex and dynamic syndrome resulting from microbial invasion and immune system dysregulation, is associated with an increased mortality, reaching up to 35% worldwide. Cholesterol metabolism is often disturbed during sepsis, with low plasma cholesterol levels being associated with poor prognosis. Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes degradation of the low-density lipoprotein receptor (LDLR), thus regulating intracellular and plasma cholesterol levels. PCSK9 is often upregulated during sepsis and might have a detrimental effect on immune host response and survival. Accordingly, PCSK9 reduces lipopolysaccharide uptake and clearance by human hepatocytes. Moreover, PCSK9 upregulation exacerbates organ dysfunction and tissue inflammation during sepsis, whereas a protective effect of PCSK9 deficiency has been documented in septic patients. Although a possible detrimental impact of PCSK9 on survival has been described, some beneficial effects of PCSK9 on immune response may be hypothesized. First, PCSK9 is associated with increased plasma cholesterol levels, which might be protective during sepsis. Second, PCSK9, by stimulating LDLR degradation and inhibiting reverse cholesterol transport (RCT), might promote preferential cholesterol accumulation in macrophages and other immune cells; these events might improve lipid raft composition and augment toll-like receptor function thus supporting inflammatory response. Hence, a more clear definition of the role of PCSK9 in septic states might provide additional insight in the understanding of the sepsis-associated immune dysregulation and enhance therapeutic outcomes. © 2017 Wiley Periodicals, Inc.

  20. The influence of abnormal thyroid function on sex hormones and bone metabolism in female patients

    Li Xiaohong; Chu Shaolin; Lei Qiufang; Ye Peihong; Chai Luhua

    2001-01-01

    Objectives: To explore the influence of hyperthyroidism and hypothyroidism on sex hormones and bone metabolism in female patients. Method: A single photon bone absorptiometry was used to measure calcareous bone mineral density (BMD) in 91 female patients with hyperthyroidism, and 37 female patients with hypothyroidism caused by Hashimoto's thyroiditis and 51 healthy female subjects with euthyroid. In addition the serum levels of BGP and PTH were determined by means of IRMA. Serum levels of FSH and E 2 were determined by RIA. Results: Serum levels of FSH , E 2 and BGP in hyperthyroidism group were significantly higher than those in control group. The serum levels of PTH were slightly lower than that in control group (P 2 and BGP were significantly lower than those in control group. The assessment of BMD showed that the prevalence rate of osteoporosis (OP) both in hyperthyroidism groups and in hypothyroidism groups was significantly higher than control group. The peak bone density in young and middle-aged female was decreased, and OP was more common in over 60-year-aged female with hypothyroidism. Conclusions: Female patients with abnormal thyroid function are often associated with abnormality of sex hormones. It leads to increasing the incidence of OP. The attack age of OP tends to be younger, especially aged patients with lymphocytic hypothyroidism increases more markedly. Therefore, BMD should be measured in all female patients with a variety of thyroid diseases

  1. Phosphatidylkojibiosyl Diglyceride: metabolism and function as an anchor in bacterial cell membrane.

    Pieringer, R A

    1975-07-01

    The recently discovered phosphoglycolipid, phosphatidylkojibiosyl diglyceride (PKD), was first observed as a biosynthetic by-product of glycosyl diglyceride metabolism in Streptococcus faecalis (faecium) ATCC 9790. Its structure is 1, 2-diacyl-3-O-alpha-Dglucopyranosyl-6'-O-phosphoryl- [1'', 2''-diacyl-3''-O-sn-glycerol]-alpha-D-glucopyranosyl)-sn-glycerol. The biosynthesis of phosphatidyl-kojibiosyl diglyceride occurs by a novel transphosphatidylation reaction in which a phosphatidyl glycerol to the primary alcohol function at the 6 position of the internal glucose of kojibiosyl diglyceride. The reaction is catalyzed by a membrane-derived enzyme. Phosphatidyl-kojibiosyl diglyceride is bound covalently through a phosphodiester bond to the polyglycerol phosphate moiety of membrane lipoteichoic acid from S. faecalis. Phosphatidylkojibiosyl diglyceride has four nonpolar long chain fatty acyl groups and appears to have the necessary physico-chemical properties to anchor the long hydrophilic glycerol phosphate polymer of lipoteichoic acid to the hydrophobic enviroment of the membrane of S. faecalis and probably other gram-positive bacteria as well.

  2. ‘Candidatus Competibacter’-lineage genomes retrieved from metagenomes reveal functional metabolic diversity

    McIlroy, Simon Jon; Albertsen, Mads; Andresen, Eva Kammer

    2014-01-01

    as for denitrification, nitrogen fixation, fermentation, trehalose synthesis and utilisation of glucose and lactate. Genetic comparison of P metabolism pathways with sequenced PAOs revealed the absence of the Pit phosphate transporter in the Competibacter-lineage genomes—identifying a key metabolic difference...

  3. Quantitative analysis of proteome and lipidome dynamics reveals functional regulation of global lipid metabolism

    Casanovas, Albert; Sprenger, Richard R; Tarasov, Kirill

    2015-01-01

    Elucidating how and to what extent lipid metabolism is remodeled under changing conditions is essential for understanding cellular physiology. Here, we analyzed proteome and lipidome dynamics to investigate how regulation of lipid metabolism at the global scale supports remodeling of cellular...

  4. Effects of isotonic and isometric exercises with mist sauna bathing on cardiovascular, thermoregulatory, and metabolic functions

    Iwase, Satoshi; Kawahara, Yuko; Nishimura, Naoki; Nishimura, Rumiko; Sugenoya, Junichi; Miwa, Chihiro; Takada, Masumi

    2014-08-01

    To clarify the effects of isometric and isotonic exercise during mist sauna bathing on the cardiovascular function, thermoregulatory function, and metabolism, six healthy young men (22 ± 1 years old, height 173 ± 4 cm, weight 65.0 ± 5.0 kg) were exposed to a mist sauna for 10 min at a temperature of 40 °C, and relative humidity of 100 % while performing or not performing ˜30 W of isometric or isotonic exercise. The effect of the exercise was assessed by measuring tympanic temperature, heart rate, systolic and diastolic blood pressure, chest sweat rate, chest skin blood flow, and plasma catecholamine and cortisol, glucose, lactate, and free fatty acid levels. Repeated measures ANOVA showed no significant differences in blood pressure, skin blood flow, sweat rate, and total amount of sweating. Tympanic temperature increased more during isotonic exercise, and heart rate increase was more marked during isotonic exercise. The changes in lactate indicated that fatigue was not very great during isometric exercise. The glucose level indicated greater energy expenditure during isometric exercise. The free fatty acid and catecholamine levels indicated that isometric exercise did not result in very great energy expenditure and stress, respectively. The results for isotonic exercise of a decrease in lactate level and an increase in plasma free fatty acid level indicated that fatigue and energy expenditure were rather large while the perceived stress was comparatively low. We concluded that isotonic exercise may be a more desirable form of exercise during mist sauna bathing given the changes in glucose and free fatty acid levels.

  5. Valsartan Improves β-Cell Function and Insulin Sensitivity in Subjects With Impaired Glucose Metabolism

    van der Zijl, Nynke J.; Moors, Chantalle C.M.; Goossens, Gijs H.; Hermans, Marc M.H.; Blaak, Ellen E.; Diamant, Michaela

    2011-01-01

    OBJECTIVE Recently, the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research Trial demonstrated that treatment with the angiotensin receptor blocker (ARB) valsartan for 5 years resulted in a relative reduction of 14% in the incidence of type 2 diabetes in subjects with impaired glucose metabolism (IGM). We investigated whether improvements in β-cell function and/or insulin sensitivity underlie these preventive effects of the ARB valsartan in the onset of type 2 diabetes. RESEARCH DESIGN AND METHODS In this randomized controlled, double-blind, two-center study, the effects of 26 weeks of valsartan (320 mg daily; n = 40) or placebo (n = 39) on β-cell function and insulin sensitivity were assessed in subjects with impaired fasting glucose and/or impaired glucose tolerance, using a combined hyperinsulinemic-euglycemic and hyperglycemic clamp with subsequent arginine stimulation and a 2-h 75-g oral glucose tolerance test (OGTT). Treatment effects were analyzed using ANCOVA, adjusting for center, glucometabolic status, and sex. RESULTS Valsartan increased first-phase (P = 0.028) and second-phase (P = 0.002) glucose-stimulated insulin secretion compared with placebo, whereas the enhanced arginine-stimulated insulin secretion was comparable between groups (P = 0.25). In addition, valsartan increased the OGTT-derived insulinogenic index (representing first-phase insulin secretion after an oral glucose load; P = 0.027). Clamp-derived insulin sensitivity was significantly increased with valsartan compared with placebo (P = 0.049). Valsartan treatment significantly decreased systolic and diastolic blood pressure compared with placebo (P valsartan treatment increased glucose-stimulated insulin release and insulin sensitivity in normotensive subjects with IGM. These findings may partly explain the beneficial effects of valsartan in the reduced incidence of type 2 diabetes. PMID:21330640

  6. Lung function and metabolic syndrome: Findings of National Health and Nutrition Examination Survey 2007–2010.

    Ford, Earl S; Cunningham, Timothy J; Mercado, Carla I

    2014-11-01

    Considerable uncertainty remains about obstructive lung function( OLF) in adults with metabolic syndrome (MetS). The aim of the present study was to examine pulmonary function status in adults with and without MetS. We used data from 3109 participants aged ≥20 years of the National Health and Nutrition Examination Survey 2007-2010. Subjects'MetS status was established on the basis of the 2009 harmonizing definition. Participants received spirometry. After age adjustment, 79.3% (SE 1.1) of participants with MetS had normal lung function, 8.7% (0.9) had restrictive lung function (RLF), 7.1% (0.8) had mild OLF, and 4.8% (0.6) had moderate OLF or worse. Among participants without MetS, these estimates were 78.7% (1.2), 3.9% (0.6), 10.9%(1.1), and 6.4% (0.8), respectively. After multiple adjustment, participants with MetS were more likely to have RLF (adjusted prevalence ratio [aPR] 2.20; 95% confidence interval [CI] 1.67, 2.90) and less likely to have any OLF (aPR 0.73; 95% CI 0.62, 0.86) than those without MetS. Furthermore, participants with MetS had lower mean levels of forced expiratory volume in one second (FEV1), FEV1 % predicted, forced vital capacity (FVC), and FVC % predicted, but a higher FEV1/FVC ratio than participants without MetS. Mean levels of FEV1, FEV1 % predicted, FVC, and FVC % predicted declined significantly, but not the FEV1/FVC ratio, as the number of components increased. Compared with adults without MetS, spirometry is more likely to show a restrictive pattern and less likely to show an obstructive pattern among adults with MetS. 2014 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

  7. Analysis of the functional gene structure and metabolic potential of microbial community in high arsenic groundwater.

    Li, Ping; Jiang, Zhou; Wang, Yanhong; Deng, Ye; Van Nostrand, Joy D; Yuan, Tong; Liu, Han; Wei, Dazhun; Zhou, Jizhong

    2017-10-15

    Microbial functional potential in high arsenic (As) groundwater ecosystems remains largely unknown. In this study, the microbial community functional composition of nineteen groundwater samples was investigated using a functional gene array (GeoChip 5.0). Samples were divided into low and high As groups based on the clustering analysis of geochemical parameters and microbial functional structures. The results showed that As related genes (arsC, arrA), sulfate related genes (dsrA and dsrB), nitrogen cycling related genes (ureC, amoA, and hzo) and methanogen genes (mcrA, hdrB) in groundwater samples were correlated with As, SO 4 2- , NH 4 + or CH 4 concentrations, respectively. Canonical correspondence analysis (CCA) results indicated that some geochemical parameters including As, total organic content, SO 4 2- , NH 4 + , oxidation-reduction potential (ORP) and pH were important factors shaping the functional microbial community structures. Alkaline and reducing conditions with relatively low SO 4 2- , ORP, and high NH 4 + , as well as SO 4 2- and Fe reduction and ammonification involved in microbially-mediated geochemical processes could be associated with As enrichment in groundwater. This study provides an overall picture of functional microbial communities in high As groundwater aquifers, and also provides insights into the critical role of microorganisms in As biogeochemical cycling. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Prioritizing Candidate Disease Metabolites Based on Global Functional Relationships between Metabolites in the Context of Metabolic Pathways

    Yang, Haixiu; Xu, Yanjun; Han, Junwei; Li, Jing; Su, Fei; Zhang, Yunpeng; Zhang, Chunlong; Li, Dongguo; Li, Xia

    2014-01-01

    Identification of key metabolites for complex diseases is a challenging task in today's medicine and biology. A special disease is usually caused by the alteration of a series of functional related metabolites having a global influence on the metabolic network. Moreover, the metabolites in the same metabolic pathway are often associated with the same or similar disease. Based on these functional relationships between metabolites in the context of metabolic pathways, we here presented a pathway-based random walk method called PROFANCY for prioritization of candidate disease metabolites. Our strategy not only takes advantage of the global functional relationships between metabolites but also sufficiently exploits the functionally modular nature of metabolic networks. Our approach proved successful in prioritizing known metabolites for 71 diseases with an AUC value of 0.895. We also assessed the performance of PROFANCY on 16 disease classes and found that 4 classes achieved an AUC value over 0.95. To investigate the robustness of the PROFANCY, we repeated all the analyses in two metabolic networks and obtained similar results. Then we applied our approach to Alzheimer's disease (AD) and found that a top ranked candidate was potentially related to AD but had not been reported previously. Furthermore, our method was applicable to prioritize the metabolites from metabolomic profiles of prostate cancer. The PROFANCY could identify prostate cancer related-metabolites that are supported by literatures but not considered to be significantly differential by traditional differential analysis. We also developed a freely accessible web-based and R-based tool at http://bioinfo.hrbmu.edu.cn/PROFANCY. PMID:25153931

  9. A dietary pattern including nopal, chia seed, soy protein, and oat reduces serum triglycerides and glucose intolerance in patients with metabolic syndrome.

    Guevara-Cruz, Martha; Tovar, Armando R; Aguilar-Salinas, Carlos A; Medina-Vera, Isabel; Gil-Zenteno, Lidia; Hernández-Viveros, Isaac; López-Romero, Patricia; Ordaz-Nava, Guillermo; Canizales-Quinteros, Samuel; Guillen Pineda, Luz E; Torres, Nimbe

    2012-01-01

    Metabolic syndrome (MetS) is a health problem throughout the world and is associated with cardiovascular disease and diabetes. Thus, the purpose of the present work was to evaluate the effects of a dietary pattern (DP; soy protein, nopal, chia seed, and oat) on the biochemical variables of MetS, the AUC for glucose and insulin, glucose intolerance (GI), the relationship of the presence of certain polymorphisms related to MetS, and the response to the DP. In this randomized trial, the participants consumed their habitual diet but reduced by 500 kcal for 2 wk. They were then assigned to the placebo (P; n = 35) or DP (n = 32) group and consumed the reduced energy diet plus the P or DP beverage (235 kcal) minus the energy provided by these for 2 mo. All participants had decreases in body weight (BW), BMI, and waist circumference during the 2-mo treatment (P < 0.0001); however, only the DP group had decreases in serum TG, C-reactive protein (CRP), and AUC for insulin and GI after a glucose tolerance test. Interestingly, participants in the DP group with MetS and the ABCA1 R230C variant had a greater decrease in BW and an increase in serum adiponectin concentration after 2 mo of dietary treatment than those with the ABCA1 R230R variant. The results from this study suggest that lifestyle interventions involving specific DP for the treatment of MetS could be more effective if local foods and genetic variations of the population are considered.

  10. Evaluation of the anti-inflammatory actions of various functional food materials including glucosamine on synovial cells.

    Yamagishi, Yoshie; Someya, Akimasa; Imai, Kensuke; Nagao, Junji; Nagaoka, Isao

    2017-08-01

    The anti-inflammatory actions of glucosamine (GlcN) on arthritic disorders involve the suppression of inflammatory mediator production from synovial cells. GlcN has also been reported to inhibit the activation of the p38 mitogen-activated protein kinase (MAPK) pathway. The present study aimed to determine the cooperative and anti‑inflammatory actions of functional food materials and evaluated the production of interleukin (IL)‑8 and phosphorylation of p38 MAPK in IL-1β-activated synovial cells, incubated with the combination of GlcN and various functional food materials containing L‑methionine (Met), undenatured type II collagen (UC‑II), chondroitin sulfate (CS), methylsulfonylmethane (MSM) and agaro-oligosaccharide (AO). The results indicated that Met, UC‑II, CS, MSM and AO slightly or moderately suppressed the IL-1β-stimulated IL‑8 production by human synovial MH7A cells. The same compounds further decreased the IL‑8 level lowered by GlcN. Similarly, they slightly suppressed the phosphorylation level of p38 MAPK and further reduced the phosphorylation level lowered by GlcN. These observations suggest a possibility that these functional food materials exert an anti‑inflammatory action (inhibition of IL‑8 production) in combination with GlcN by cooperatively suppressing the p38 MAPK signaling (phosphorylation).

  11. Salmonella Persistence in Tomatoes Requires a Distinct Set of Metabolic Functions Identified by Transposon Insertion Sequencing

    Desai, Prerak; Porwollik, Steffen; Canals, Rocio; Perez, Daniel R.; Chu, Weiping; McClelland, Michael; Teplitski, Max

    2016-01-01

    ABSTRACT Human enteric pathogens, such as Salmonella spp. and verotoxigenic Escherichia coli, are increasingly recognized as causes of gastroenteritis outbreaks associated with the consumption of fruits and vegetables. Persistence in plants represents an important part of the life cycle of these pathogens. The identification of the full complement of Salmonella genes involved in the colonization of the model plant (tomato) was carried out using transposon insertion sequencing analysis. With this approach, 230,000 transposon insertions were screened in tomato pericarps to identify loci with reduction in fitness, followed by validation of the screen results using competition assays of the isogenic mutants against the wild type. A comparison with studies in animals revealed a distinct plant-associated set of genes, which only partially overlaps with the genes required to elicit disease in animals. De novo biosynthesis of amino acids was critical to persistence within tomatoes, while amino acid scavenging was prevalent in animal infections. Fitness reduction of the Salmonella amino acid synthesis mutants was generally more severe in the tomato rin mutant, which hyperaccumulates certain amino acids, suggesting that these nutrients remain unavailable to Salmonella spp. within plants. Salmonella lipopolysaccharide (LPS) was required for persistence in both animals and plants, exemplifying some shared pathogenesis-related mechanisms in animal and plant hosts. Similarly to phytopathogens, Salmonella spp. required biosynthesis of amino acids, LPS, and nucleotides to colonize tomatoes. Overall, however, it appears that while Salmonella shares some strategies with phytopathogens and taps into its animal virulence-related functions, colonization of tomatoes represents a distinct strategy, highlighting this pathogen's flexible metabolism. IMPORTANCE Outbreaks of gastroenteritis caused by human pathogens have been increasingly associated with foods of plant origin, with tomatoes

  12. Deoxynivalenol as a contaminant of broiler feed: intestinal development, absorptive functionality, and metabolism of the mycotoxin.

    Yunus, A W; Blajet-Kosicka, A; Kosicki, R; Khan, M Z; Rehman, H; Böhm, J

    2012-04-01

    Deoxynivalenol (DON) has been recently documented to deteriorate intestinal morphology in chickens at dietary doses that are regarded as safe for this species. The present trial was conducted to explore the significance of these morphological changes in relation to intestinal absorptive functionality and DON metabolism. Ross broilers at 7 d of age were fed either a basal diet (0.265 ± 0.048 mg of DON/kg; 0.013 ± 0.001 mg of zearalenone/kg), a low DON diet (1.68 mg of DON/kg; 0.145 ± 0.007 mg of zearalenone/kg), or a high DON diet (12.209 ± 1.149 mg of DON/kg; 1.094 ± 0.244 mg of zearalenone/kg). The DON diets (to variable degrees) progressively decreased the relative density (weight:length) of the small intestine with increasing exposure length, which could be correlated with a decrease in villus height in the small intestine. Short circuit current of the jejunal epithelium, reflecting transport function of the epithelium per unit area, was reduced (P = 0.001) in the birds fed the high DON diet. The increasing dietary level of DON linearly (P = 0.035) increased the length of the jejunum in wk 4 of exposure, resulting in conservation of macronutrient retention. Upon challenging the birds with a fixed amount of DON after wk 5 of exposure, higher (P ≤ 0.033) amounts of DON and the detoxification metabolite (de-epoxy-DON) were found at 5 h postchallenge in the guts of birds raised on the DON diets. The increasing level of previous exposure to DON linearly (P = 0.040) decreased the plasma level of DON in the birds at 1 h postchallenge. The amounts of zearalenone and its analogs in the gut and plasma also followed a trend similar to that for DON. These data suggest that intestines in chickens may adapt to a chronic DON challenge by morphological and functional modifications. The birds having previous exposure to Fusarium mycotoxins showed moderate detoxification coupled with reduced transfer of the mycotoxins to systemic circulation. Some metabolites of

  13. Metabolism of Citrate and Other Carboxylic Acids in Erythrocytes As a Function of Oxygen Saturation and Refrigerated Storage

    Travis Nemkov

    2017-10-01

    Full Text Available State-of-the-art proteomics technologies have recently helped to elucidate the unanticipated complexity of red blood cell metabolism. One recent example is citrate metabolism, which is catalyzed by cytosolic isoforms of Krebs cycle enzymes that are present and active in mature erythrocytes and was determined using quantitative metabolic flux analysis. In previous studies, we reported significant increases in glycolytic fluxes in red blood cells exposed to hypoxia in vitro or in vivo, an observation relevant to transfusion medicine owing to the potential benefits associated with hypoxic storage of packed red blood cells. Here, using a combination of steady state and quantitative tracing metabolomics experiments with 13C1,2,3-glucose, 13C6-citrate, 13C515N2-glutamine, and 13C1-aspartate via ultra-high performance liquid chromatography coupled on line with mass spectrometry, we observed that hypoxia in vivo and in vitro promotes consumption of citrate and other carboxylates. These metabolic reactions are theoretically explained by the activity of cytosolic malate dehydrogenase 1 and isocitrate dehydrogenase 1 (abundantly represented in the red blood cell proteome, though moonlighting functions of additional enzymes cannot be ruled out. These observations enhance understanding of red blood cell metabolic responses to hypoxia, which could be relevant to understand systemic physiological and pathological responses to high altitude, ischemia, hemorrhage, sepsis, pulmonary hypertension, or hemoglobinopathies. Results from this study will also inform the design and testing of novel additive solutions that optimize red blood cell storage under oxygen-controlled conditions.

  14. Physical fitness and activity, metabolic profile, adipokines and endothelial function in children.

    Penha, Jociene Terra da; Gazolla, Fernanda Mussi; Carvalho, Cecília Noronha de Miranda; Madeira, Isabel Rey; Rodrigues-Junior, Flávio; Machado, Elisabeth de Amorim; Sicuro, Fernando Lencastre; Farinatti, Paulo; Bouskela, Eliete; Collett-Solberg, Paulo Ferrez

    2018-05-29

    The prevalence of obesity is increasing. The aim of this study was to investigate if there is endothelial dysfunction in children with normal or excess weight, and whether the metabolic profile, adipokines, and endothelial dysfunction would be more strongly associated with physical fitness or with physical activity levels. Cross-sectional study involving children aged 5-12 years. The evaluation included venous occlusion plethysmography, serum levels of adiponectin, leptin and insulin, lipid profile, physical activity score (PAQ-C questionnaire), and physical fitness evaluation (Yo-Yo test). A total of 62 children participated in this study. Based on the body mass index, 27 were eutrophic, 10 overweight and 25 obese. Triglycerides, LDL cholesterol, HOMA-IR, and leptin were higher in the obese and excess-weight groups compared to the eutrophic group (pPAQ-C. The Yo-Yo test was significantly associated with HDL cholesterol (rho=-0.41; p=0.01), and this association remained after adjusting for body mass index z-score (rho=0.28; p=0.03). This study showed that endothelial dysfunction is already present in obese children, suggesting a predisposition to atherosclerotic disease. Moreover, HDL cholesterol levels were correlated with physical fitness, regardless of body mass index. Copyright © 2018. Published by Elsevier Editora Ltda.

  15. Insulin in the nervous system and the mind: Functions in metabolism, memory, and mood

    Lee, Seung-Hwan; Zabolotny, Janice M.; Huang, Hu; Lee, Hyon; Kim, Young-Bum

    2016-01-01

    Background: Insulin, a pleotrophic hormone, has diverse effects in the body. Recent work has highlighted the important role of insulin's action in the nervous system on glucose and energy homeostasis, memory, and mood. Scope of review: Here we review experimental and clinical work that has broadened the understanding of insulin's diverse functions in the central and peripheral nervous systems, including glucose and body weight homeostasis, memory and mood, with particular emphasis on intra...

  16. High-throughput metabolic state analysis: The missing link in integrated functional genomics of yeasts

    Villas-Bôas, Silas Granato; Moxley, Joel. F; Åkesson, Mats Fredrik

    2005-01-01

    that achieve comparable throughput, effort and cost compared with DNA arrays. Our sample workup method enables simultaneous metabolite measurements throughout central carbon metabolism and amino acid biosynthesis, using a standard GC-MS platform that was optimized for this Purpose. As an implementation proof......-of-concept, we assayed metabolite levels in two yeast strains and two different environmental conditions in the context of metabolic pathway reconstruction. We demonstrate that these differential metabolite level data distinguish among sample types, such as typical metabolic fingerprinting or footprinting. More...

  17. Changes in Regional Adiposity and Cardio-Metabolic Function Following a Weight Loss Program with Sibutramine in Obese Men with Obstructive Sleep Apnea

    Phillips, Craig L.; Yee, Brendon J.; Trenell, Mike I.; Magnussen, John S.; Wang, David; Banerjee, Dev; Berend, Norbert; Grunstein, Ronald R.

    2009-01-01

    Background: Although obstructive sleep apnea (OSA) is strongly linked with obesity, both conditions have been associated with increased cardiovascular risk including glucose intolerance, dyslipidemia, and hypertension independent of one another. Weight loss is known to improve both cardiovascular risk and OSA severity. The aim of this study was to evaluate cardiovascular and metabolic changes, including compartment-specific fat loss in obese OSA subjects undergoing a weight loss program. Design: Observational study. Participants: 93 men with moderate-severe OSA. Interventions: 6-month open-label weight loss trial combining sibutramine (a serotonin and noradrenaline reuptake inhibitor) with a 600-kcal deficit diet and exercise. Measurements and Results: At baseline and following 6 months of weight loss, OSA was assessed together with CT-quantified intra-abdominal and liver fat and markers of metabolic and cardiovascular function. At 6 months, weight loss and improvements in OSA were accompanied by improved insulin resistance (HOMA), increased HDL cholesterol, and reduced total cholesterol/HDL ratio. There were also reductions in measures of visceral and subcutaneous abdominal fat and liver fat. Reductions in liver fat and sleep time spent below 90% oxyhemoglobin saturation partly explained the improvement in HOMA (R2 = 0.18). In contrast, arterial stiffness (aortic augmentation index), heart rate, blood pressure, and total cholesterol did not change. Conclusions: Weight loss with sibutramine was associated with improvements in metabolic and body composition risk factors but not blood pressure or arterial stiffness. Improved insulin resistance was partly associated with reductions in liver fat and hypoxemia associated with sleep apnea. Citation: Phillips CL; Yee BJ; Trenell MI; Magnussen JS; Wang D; Banerjee D; Berend N; Grunstein RR. Changes in regional adiposity and cardio-metabolic function following a weight loss program with sibutramine in obese men with

  18. The impact of breaking up prolonged sitting on glucose metabolism and cognitive function when sleep is restricted

    Grace E. Vincent

    2018-01-01

    Conclusions: There were no observable benefits of breaking up prolonged sitting on glucose metabolism under conditions of sleep restriction. These findings have implications for behaviour change interventions. Future studies will need to include larger, less homogenous study populations and appropriate control conditions (i.e., 8–9 h sleep opportunities.

  19. Rescue of heart lipoprotein lipase-knockout mice confirms a role for triglyceride in optimal heart metabolism and function.

    Khan, Raffay S; Lin, Yan; Hu, Yunying; Son, Ni-Huiping; Bharadwaj, Kalyani G; Palacios, Carla; Chokshi, Aalap; Ji, Ruiping; Yu, Shuiqing; Homma, Sunichi; Schulze, P Christian; Tian, Rong; Goldberg, Ira J

    2013-12-01

    Hearts utilize fatty acids as a primary source of energy. The sources of those lipids include free fatty acids and lipoprotein triglycerides. Deletion of the primary triglyceride-hydrolyzing enzyme lipoprotein lipase (LPL) leads to cardiac dysfunction. Whether heart LPL-knockout (hLPL0) mice are compromised due a deficiency in energetic substrates is unknown. To test whether alternative sources of energy will prevent cardiac dysfunction in hLPL0 mice, two different models were used to supply nonlipid energy. 1) hLPL0 mice were crossed with mice transgenically expressing GLUT1 in cardiomyocytes to increase glucose uptake into the heart; this cross-corrected cardiac dysfunction, reduced cardiac hypertrophy, and increased myocardial ATP. 2) Mice were randomly assigned to a sedentary or training group (swimming) at 3 mo of age, which leads to increased skeletal muscle production of lactate. hLPL0 mice had greater expression of the lactate transporter monocarboxylate transporter-1 (MCT-1) and increased cardiac lactate uptake. Compared with hearts from sedentary hLPL0 mice, hearts from trained hLPL0 mice had adaptive hypertrophy and improved cardiac function. We conclude that defective energy intake and not the reduced uptake of fat-soluble vitamins or cholesterol is responsible for cardiac dysfunction in hLPL0 mice. In addition, our studies suggest that adaptations in cardiac metabolism contribute to the beneficial effects of exercise on the myocardium of patients with heart failure.

  20. Arterial function parameters in patients with metabolic syndrome and severe hypertriglyceridemia.

    Rinkūnienė, Egidija; Butkutė, Eglė; Puronaitė, Roma; Petrulionienė, Žaneta; Dženkevičiūtė, Vilma; Kasiulevičius, Vytautas; Laucevičius, Aleksandras

    Hypertriglyceridemia (hTG) is 1 of the dyslipidemia manifestations in patients with metabolic syndrome (MetS). However, for several decades, the role of hTG in cardiovascular risk was not well established. The aim of this study was to assess the parameters of the vascular structure and function in patients with MetS and different degree of hTG. Patients (aged 40-65 years) with MetS were divided into 3 groups by triglyceride (TG) levels according to National Cholesterol Education Program Adult Treatment Panel III Guidelines: severe hTG (TG ≥ 500 mg/dL), moderate hTG (TG 200-499 mg/dL), and a control (TG severe TG was observed in 9.6% (n = 100) of patients. Overall TG concentration was 231.17 ± 184.23 mg/dL; in severe hTG group, TG concentration was 795.36 ± 368.45 mg/dL, in moderate hTG group 285.20 ± 70.86 mg/dL, and 112.48 ± 24.80 mg/dL in control group. AIxHR75 and IMT were the lowest in the severe hTG group (P severe hTG have lower IMT and AIxHR75 and higher PWV and mean arterial pressure. Many factors could affect arterial parameters, and more research are needed to investigate arterial parameters and hTG connection. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  1. Steady state peripheral blood provides cells with functional and metabolic characteristics of real hematopoietic stem cells.

    Bourdieu, Antonin; Avalon, Maryse; Lapostolle, Véronique; Ismail, Sadek; Mombled, Margaux; Debeissat, Christelle; Guérinet, Marianne; Duchez, Pascale; Chevaleyre, Jean; Vlaski-Lafarge, Marija; Villacreces, Arnaud; Praloran, Vincent; Ivanovic, Zoran; Brunet de la Grange, Philippe

    2018-01-01

    Hematopoietic stem cells (HSCs), which are located in the bone marrow, also circulate in cord and peripheral blood. Despite high availability, HSCs from steady state peripheral blood (SSPB) are little known and not used for research or cell therapy. We thus aimed to characterize and select HSCs from SSPB by a direct approach with a view to delineating their main functional and metabolic properties and the mechanisms responsible for their maintenance. We chose to work on Side Population (SP) cells which are highly enriched in HSCs in mouse, human bone marrow, and cord blood. However, no SP cells from SSBP have as yet been characterized. Here we showed that SP cells from SSPB exhibited a higher proliferative capacity and generated more clonogenic progenitors than non-SP cells in vitro. Furthermore, xenotransplantation studies on immunodeficient mice demonstrated that SP cells are up to 45 times more enriched in cells with engraftment capacity than non-SP cells. From a cell regulation point of view, we showed that SP activity depended on O 2 concentrations close to those found in HSC niches, an effect which is dependent on both hypoxia-induced factors HIF-1α and HIF-2α. Moreover SP cells displayed a reduced mitochondrial mass and, in particular, a lower mitochondrial activity compared to non-SP cells, while they exhibited a similar level of glucose incorporation. These results provided evidence that SP cells from SSPB displayed properties of very primitive cells and HSC, thus rendering them an interesting model for research and cell therapy. © 2017 Wiley Periodicals, Inc.

  2. The Effects of Liver Transplantation on the Bone Metabolism and Gonadal Functions

    Funda Atamaz

    2005-06-01

    Full Text Available The present study was designed to evaluate the effects of liver transplantation (LT on the bone mineral density (BMD, characteristics of bone turnover, mineral metabolism and sex hormons. Fifty one patients (34 men, 11 women aged 43.5 ± 12.1, who underwent LT were studied, assessing the following parameters: lumbar spine and proximal femur BMD, osteocalcin, deoxypyridinoline (DPD, parathyroid hormone (PTH, free testesterone (FT, gonadotropins (FSH, LH, tyroid hormones, growth hormone (GH and blood/ 24-hours urine Ca and P. All the measures were obtained at baseline and at 3rd month after LT. At baseline, 12 patients (%23.5 had osteoporosis, 22 patients (%43.1 had osteopenia and the mean BMD was 0.892 ± 0.1 for lumbar spine. Whereas, osteoporosis was seen less at femoral neck and total femur: 5 (%9.8 and 4 (%7.8, respectively. Three months after LT, 3.9% drop for lumbar spine, 5.3% drop for femur neck, 6.3% drop for total femur were observed, in BMD these decreases were statistically significant for all sites (p<0.05. The thyroid hormones, GH, PTH, blood Ca, P and osteocalcin levels and urinary DPD excretion were within normal range, while the levels of FSH and LH in women and level of FT in men were lower than normal range. After LT, statistically significant increases were observed in the PTH, osteocalcin, DPD, FSH, LH and FT levels (p<0.05. There was a highly significant negative correlation between duration of liver disease and all the BMD measures (p<0.01. Consequently, the increased osteoporosis ratio which was characterized by high bone turnover was found in patients who underwent LT in this study. The normalization of liver functions following LT was characterized by an early rise in sex hormones.

  3. Insulin in the nervous system and the mind: Functions in metabolism, memory, and mood

    Seung-Hwan Lee

    2016-08-01

    Major conclusions: Implications for the treatment of obesity, type 2 diabetes, dementia, and mood disorders are discussed in the context of brain insulin action. Intranasal insulin may have potential in the treatment of central nervous system-related metabolic disorders.

  4. Antibiotic-Induced Changes to the Host Metabolic Environment Inhibit Drug Efficacy and Alter Immune Function

    Yang, Jason H.; Bhargava, Prerna; McCloskey, Douglas

    2017-01-01

    Bactericidal antibiotics alter microbial metabolism as part of their lethality and can damage mitochondria in mammalian cells. In addition, antibiotic susceptibility is sensitive to extracellular metabolites, but it remains unknown whether metabolites present at an infection site can affect eithe...

  5. Astrocytes and energy metabolism.

    Prebil, Mateja; Jensen, Jørgen; Zorec, Robert; Kreft, Marko

    2011-05-01

    Astrocytes are glial cells, which play a significant role in a number of processes, including the brain energy metabolism. Their anatomical position between blood vessels and neurons make them an interface for effective glucose uptake from blood. After entering astrocytes, glucose can be involved in different metabolic pathways, e.g. in glycogen production. Glycogen in the brain is localized mainly in astrocytes and is an important energy source in hypoxic conditions and normal brain functioning. The portion of glucose metabolized into glycogen molecules in astrocytes is as high as 40%. It is thought that the release of gliotransmitters (such as glutamate, neuroactive peptides and ATP) into the extracellular space by regulated exocytosis supports a significant part of communication between astrocytes and neurons. On the other hand, neurotransmitter action on astrocytes has a significant role in brain energy metabolism. Therefore, understanding the astrocytes energy metabolism may help understanding neuron-astrocyte interactions.

  6. Gender, renal function, and outcomes on the liver transplant waiting list: assessment of revised MELD including estimated glomerular filtration rate.

    Myers, Robert P; Shaheen, Abdel Aziz M; Aspinall, Alexander I; Quinn, Robert R; Burak, Kelly W

    2011-03-01

    The Model for End-Stage Liver Disease (MELD) allocation system for liver transplantation (LT) may present a disadvantage for women by including serum creatinine, which is typically lower in females. Our objectives were to investigate gender disparities in outcomes among LT candidates and to assess a revised MELD, including estimated glomerular filtration rate (eGFR), for predicting waiting list mortality. Adults registered for LT between 2002 and 2007 were identified using the UNOS database. We compared components of MELD, MDRD-derived eGFR, and the 3-month probability of LT and death between genders. Discrimination of MELD, MELDNa, and revised models including eGFR for mortality were compared using c-statistics. A total of 40,393 patients (36% female) met the inclusion criteria; 9% died and 24% underwent LT within 3 months of listing. Compared with men, women had lower median serum creatinine (0.9 vs. 1.0 mg/dl), eGFR (72 vs. 83 ml/min/1.73 m(2)), and mean MELD (16.5 vs. 17.2; all p discrimination for 3-month mortality (c-statistics: MELD 0.896, MELD-eGFR 0.894, MELDNa 0.911, MELDNa-eGFR 0.905). Women are disadvantaged under MELD potentially due to its inclusion of creatinine. However, since including eGFR in MELD does not improve mortality prediction, alternative refinements are necessary. Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  7. Ramadan model of intermittent fasting for 28 d had no major effect on body composition, glucose metabolism, or cognitive functions in healthy lean men

    Harder-Lauridsen, Nina M.; Rosenberg, Astrid; Benatti, Fabiana B.; Damm, Julie A.; Thomsen, Carsten; Mortensen, Erik L.; Pedersen, Bente K.; Krogh-Madsen, Rikke

    2017-01-01

    Objectives: There has been a parallel increase in the incidence of obesity and diabetes as well as the number of daily meals. However, evidence is lacking regarding the role of intermittent fasting. The aim of this study was to determine the effects of a Ramadan model of intermittent fasting (RIF; 14 h of daytime abstinence from food and drinking) for 28 d on body composition, glucose metabolism, and cognitive function. Methods: Ten healthy, lean men were included in a nonrandomized, crossove...

  8. Altered Transport and Metabolism of Phenolic Compounds in Obesity and Diabetes: Implications for Functional Food Development and Assessment12

    Redan, Benjamin W; Buhman, Kimberly K; Novotny, Janet A; Ferruzzi, Mario G

    2016-01-01

    Interest in the application of phenolic compounds from the diet or supplements for the prevention of chronic diseases has grown substantially, but the efficacy of such approaches in humans is largely dependent on the bioavailability and metabolism of these compounds. Although food and dietary factors have been the focus of intense investigation, the impact of disease states such as obesity or diabetes on their absorption, metabolism, and eventual efficacy is important to consider. These factors must be understood in order to develop effective strategies that leverage bioactive phenolic compounds for the prevention of chronic disease. The goal of this review is to discuss the inducible metabolic systems that may be influenced by disease states and how these effects impact the bioavailability and metabolism of dietary phenolic compounds. Because current studies generally report that obesity and/or diabetes alter the absorption and excretion of these compounds, this review includes a description of the absorption, conjugation, and excretion pathways for phenolic compounds and how they are potentially altered in disease states. A possible mechanism that will be discussed related to the modulation of phenolic bioavailability and metabolism may be linked to increased inflammatory status from increased amounts of adipose tissue or elevated plasma glucose concentrations. Although more studies are needed, the translation of benefits derived from dietary phenolic compounds to individuals with obesity or diabetes may require the consideration of dosing strategies or be accompanied by adjunct therapies to improve the bioavailability of these compounds. PMID:28140326

  9. The Effects of Different Isocaloric Oral Nutrient Solutions on Psychophysical, Metabolic, Cognitive, and Olfactory Function in Young Male Subjects

    Bachlechner, Stephan; Denzer-Lippmann, Melanie Y.; Wielopolski, Jan; Fischer, Marie; Buettner, Andrea; Doerfler, Arndt; Schöfl, Christof; Münch, Gerald; Kornhuber, Johannes; Thürauf, Norbert

    2017-01-01

    Food intake influences human cognition, olfaction, hunger, and food craving. However, little research has been done in this field to elucidate the effects of different nutrients. Thus, the goal of our study was to investigate the effects of oral ingestion of different nutrient solutions on olfactory, cognitive, metabolic and psychophysical function. Twenty healthy men participated in our study employing a double-blind, cross-over, repeated measurement design. Participants were tested on four ...

  10. Kidney transplantation improves arterial function measured by pulse wave analysis and endothelium-independent dilatation in uraemic patients despite deterioration of glucose metabolism

    Hornum, Mads; Clausen, Peter; Idorn, Thomas

    2011-01-01

    for kidney transplantation (uraemic control group, age 47 ± 11 years). Arterial function was estimated by the pulse wave velocity (PWV) of the carotid-femoral pulse wave, aortic augmentation index (AIX), flow-mediated (FMD) and nitroglycerin-induced vasodilatation (NID) of the brachial artery performed......BACKGROUND: The aim of this study is to investigate the effect of kidney transplantation on arterial function in relation to changes in glucose metabolism. METHODS: Included were 40 kidney recipients (Tx group, age 38 ± 13 years) and 40 patients without known diabetes remaining on the waiting list...... before transplantation and after 12 months. PWV recorded sequentially at the carotid and femoral artery is an estimate of arterial stiffness; AIX is an integrated index of vascular and ventricular function. FMD and NID are the dilatory capacities of the brachial artery after increased flow (endothelium...

  11. Prevalence of metabolic syndrome and its association with lower urinary tract symptoms and sexual function.

    Plata, M; Caicedo, J I; Trujillo, C G; Mariño-Alvarez, Á M; Fernandez, N; Gutierrez, A; Godoy, F; Cabrera, M; Cataño-Cataño, J G; Robledo, D

    2017-10-01

    To estimate the frequency of metabolic syndrome (MetS) in a daily urology practice and to determine its association with lower urinary tract symptoms (LUTS) and erectile dysfunction (ED). A retrospective study was conducted. Data from all male patients aged ≥40 years who attended our outpatient urology clinic from 2010 to 2011 was collected. Prevalence of MetS was determined, and LUTS and ED were assessed. A logistic model was used to determine possible associations, controlling for confounders and interaction factors. A total of 616 patients were included. MetS was observed in 43.8% (95% CI 39.6-48.3). The bivariate model showed an association between MetS and LUTS (p<0.01), but not between MetS and ED. The logistic model showed an association between MetS and the International Prostate Symptom Score (IPSS), while controlling for other variables. Patients exhibiting moderate LUTS had a greater risk for MetS than patients with mild LUTS (OR 1.83, 95% CI 1.14-2.94). After analyzing for individual components of MetS, positive associations were found between diabetes and severe LUTS (OR 1.3, 95% CI 1.24-7.1), and between diabetes and ED (OR 2.57, 95% CI 1.12-5.8). This study was able to confirm an association between MetS and LUTS, but not for ED. Specific components such as diabetes were associated to both. Geographical differences previously reported in the literature might account for these findings. Given that MetS is frequent among urological patients, it is advisable that urologists actively screen for it. Copyright © 2017 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. Functional imaging to monitor vascular and metabolic response in canine head and neck tumors during fractionated radiotherapy.

    Rødal, Jan; Rusten, Espen; Søvik, Åste; Skogmo, Hege Kippenes; Malinen, Eirik

    2013-10-01

    Radiotherapy causes alterations in tumor biology, and non-invasive early assessment of such alterations may become useful for identifying treatment resistant disease. The purpose of the current work is to assess changes in vascular and metabolic features derived from functional imaging of canine head and neck tumors during fractionated radiotherapy. Material and methods. Three dogs with spontaneous head and neck tumors received intensity-modulated radiotherapy (IMRT). Contrast-enhanced cone beam computed tomography (CE-CBCT) at the treatment unit was performed at five treatment fractions. Dynamic (18)FDG-PET (D-PET) was performed prior to the start of radiotherapy, at mid-treatment and at 3-12 weeks after the completion of treatment. Tumor contrast enhancement in the CE-CBCT images was used as a surrogate for tumor vasculature. Vascular and metabolic tumor parameters were further obtained from the D-PET images. Changes in these tumor parameters were assessed, with emphasis on intra-tumoral distributions. Results. For all three patients, metabolic imaging parameters obtained from D-PET decreased from the pre- to the inter-therapy session. Correspondingly, for two of three patients, vascular imaging parameters obtained from both CE-CBCT and D-PET increased. Only one of the tumors showed a clear metabolic response after therapy. No systematic changes in the intra-tumor heterogeneity in the imaging parameters were found. Conclusion. Changes in vascular and metabolic parameters could be detected by the current functional imaging methods. Vascular tumor features from CE-CBCT and D-PET corresponded well. CE-CBCT is a potential method for easy response assessment when the patient is at the treatment unit.

  13. Distinct Metabolic Requirements of Exhausted and Functional Virus-Specific CD8 T Cells in the Same Host.

    Schurich, Anna; Pallett, Laura J; Jajbhay, Danyal; Wijngaarden, Jessica; Otano, Itziar; Gill, Upkar S; Hansi, Navjyot; Kennedy, Patrick T; Nastouli, Eleni; Gilson, Richard; Frezza, Christian; Henson, Sian M; Maini, Mala K

    2016-08-02

    T cells undergo profound metabolic changes to meet the increased energy demands of maintaining an antiviral response. We postulated that differences in metabolic reprogramming would shape the efficacy of CD8 T cells mounted against persistent viral infections. We found that the poorly functional PD-1(hi) T cell response against hepatitis B virus (HBV) had upregulated the glucose transporter, Glut1, an effect recapitulated by oxygen deprivation to mimic the intrahepatic environment. Glut1(hi) HBV-specific T cells were dependent on glucose supplies, unlike the more functional cytomegalovirus (CMV)-specific T cells that could utilize oxidative phosphorylation in the absence of glucose. The inability of HBV-specific T cells to switch to oxidative phosphorylation was accompanied by increased mitochondrial size and lower mitochondrial potential, indicative of mitochondrial dysfunction. Interleukin (IL)-12, which recovers HBV-specific T cell effector function, increased their mitochondrial potential and reduced their dependence on glycolysis. Our findings suggest that mitochondrial defects limit the metabolic plasticity of exhausted HBV-specific T cells. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  14. Endothelial cell-derived matrix promotes the metabolic functional maturation of hepatocyte via integrin-Src signalling.

    Guo, Xinyue; Li, Weihong; Ma, Minghui; Lu, Xin; Zhang, Haiyan

    2017-11-01

    The extracellular matrix (ECM) microenvironment is involved in the regulation of hepatocyte phenotype and function. Recently, the cell-derived extracellular matrix has been proposed to represent the bioactive and biocompatible materials of the native ECM. Here, we show that the endothelial cell-derived matrix (EC matrix) promotes the metabolic maturation of human adipose stem cell-derived hepatocyte-like cells (hASC-HLCs) through the activation of the transcription factor forkhead box protein A2 (FOXA2) and the nuclear receptors hepatocyte nuclear factor 4 alpha (HNF4α) and pregnane X receptor (PXR). Reducing the fibronectin content in the EC matrix or silencing the expression of α5 integrin in the hASC-HLCs inhibited the effect of the EC matrix on Src phosphorylation and hepatocyte maturation. The inhibition of Src phosphorylation using the inhibitor PP2 or silencing the expression of Src in hASC-HLCs also attenuated the up-regulation of the metabolic function of hASC-HLCs in a nuclear receptor-dependent manner. These data elucidate integrin-Src signalling linking the extrinsic EC matrix signals and metabolic functional maturation of hepatocyte. This study provides a model for studying the interaction between hepatocytes and non-parenchymal cell-derived matrix. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  15. Distinct Metabolic Requirements of Exhausted and Functional Virus-Specific CD8 T Cells in the Same Host

    Anna Schurich

    2016-08-01

    Full Text Available T cells undergo profound metabolic changes to meet the increased energy demands of maintaining an antiviral response. We postulated that differences in metabolic reprogramming would shape the efficacy of CD8 T cells mounted against persistent viral infections. We found that the poorly functional PD-1hi T cell response against hepatitis B virus (HBV had upregulated the glucose transporter, Glut1, an effect recapitulated by oxygen deprivation to mimic the intrahepatic environment. Glut1hi HBV-specific T cells were dependent on glucose supplies, unlike the more functional cytomegalovirus (CMV-specific T cells that could utilize oxidative phosphorylation in the absence of glucose. The inability of HBV-specific T cells to switch to oxidative phosphorylation was accompanied by increased mitochondrial size and lower mitochondrial potential, indicative of mitochondrial dysfunction. Interleukin (IL-12, which recovers HBV-specific T cell effector function, increased their mitochondrial potential and reduced their dependence on glycolysis. Our findings suggest that mitochondrial defects limit the metabolic plasticity of exhausted HBV-specific T cells.

  16. Elevated CO2 shifts the functional structure and metabolic potentials of soil microbial communities in a C4 agroecosystem.

    Xiong, Jinbo; He, Zhili; Shi, Shengjing; Kent, Angela; Deng, Ye; Wu, Liyou; Van Nostrand, Joy D; Zhou, Jizhong

    2015-03-20

    Atmospheric CO2 concentration is continuously increasing, and previous studies have shown that elevated CO2 (eCO2) significantly impacts C3 plants and their soil microbial communities. However, little is known about effects of eCO2 on the compositional and functional structure, and metabolic potential of soil microbial communities under C4 plants. Here we showed that a C4 maize agroecosystem exposed to eCO2 for eight years shifted the functional and phylogenetic structure of soil microbial communities at both soil depths (0-5 cm and 5-15 cm) using EcoPlate and functional gene array (GeoChip 3.0) analyses. The abundances of key genes involved in carbon (C), nitrogen (N) and phosphorus (P) cycling were significantly stimulated under eCO2 at both soil depths, although some differences in carbon utilization patterns were observed between the two soil depths. Consistently, CO2 was found to be the dominant factor explaining 11.9% of the structural variation of functional genes, while depth and the interaction of depth and CO2 explained 5.2% and 3.8%, respectively. This study implies that eCO2 has profound effects on the functional structure and metabolic potential/activity of soil microbial communities associated with C4 plants, possibly leading to changes in ecosystem functioning and feedbacks to global change in C4 agroecosystems.

  17. Synthesis, secretion, function, metabolism and application of natriuretic peptides in heart failure

    Fu, Shihui; Ping, Ping; Wang, Fengqi; Luo, Leiming

    2018-01-01

    As a family of hormones with pleiotropic effects, natriuretic peptide (NP) system includes atrial NP (ANP), B-type NP (BNP), C-type NP (CNP), dendroaspis NP and urodilatin, with NP receptor-A (guanylate cyclase-A), NP receptor-B (guanylate cyclase-B) and NP receptor-C (clearance receptor). These peptides are genetically distinct, but structurally and functionally related for regulating circulatory homeostasis in vertebrates. In humans, ANP and BNP are encoded by NP precursor A (NPPA) and NPPB...

  18. Dynamic relationship between neurostimulation and N-acetylaspartate metabolism in the human visual cortex: evidence that NAA functions as a molecular water pump during visual stimulation.

    Baslow, Morris H; Hrabe, Jan; Guilfoyle, David N

    2007-01-01

    N-acetyl-l-aspartic acid (NAA), an amino acid synthesized and stored primarily in neurons in the brain, has been proposed to be a molecular water pump (MWP) whose function is to rapidly remove water from neurons against a water gradient. In this communication, we describe the results of a functional (1)H proton magnetic resonance spectroscopy (fMRS) study, and provide evidence that in the human visual cortex, over a 10-min period of visual stimulation, there are stimulation-induced graded changes in the NAA MRS signal from that of a preceding 10-min baseline period with a decline in the NAA signal of 13.1% by the end of the 10-min stimulation period. Upon cessation of visual stimulation, the NAA signal gradually increases during a 10-min recovery period and once again approaches the baseline level. Because the NAA MRS signal reflects the NAA concentration, these changes indicate rapid focal changes in its concentration, and transient changes in its intercompartmental metabolism. These include its rates of synthesis and efflux from neurons and its hydrolysis by oligodendrocytes. During stimulation, the apparent rate of NAA efflux and hydrolysis increased 14.2 times, from 0.55 to 7.8 micromol g(-1) h(-1). During recovery, the apparent rate of synthesis increased 13.3 times, from 0.55 to 7.3 micromol g(-1) h(-1). The decline in the NAA signal during stimulation suggests that a rapid increase in the rate of NAA-obligated water release to extracellular fluid (ECF) is the initial and seminal event in response to neurostimulation. It is concluded that the NAA metabolic cycle in the visual cortex is intimately linked to rates of neuronal signaling, and that the functional cycle of NAA is associated with its release to ECF, thus supporting the hypothesis that an important function of the NAA metabolic cycle is that of an efflux MWP.

  19. An in silico assessment of gene function and organization of the phenylpropanoid pathway metabolic networks in Arabidopsis thaliana and limitations thereof

    Costa, Michael A.; Collins, R. Eric; Anterola, Aldwin M.; Cochrane, Fiona C.; Davin, Laurence B.; Lewis, Norman G.

    2003-01-01

    The Arabidopsis genome sequencing in 2000 gave to science the first blueprint of a vascular plant. Its successful completion also prompted the US National Science Foundation to launch the Arabidopsis 2010 initiative, the goal of which is to identify the function of each gene by 2010. In this study, an exhaustive analysis of The Institute for Genomic Research (TIGR) and The Arabidopsis Information Resource (TAIR) databases, together with all currently compiled EST sequence data, was carried out in order to determine to what extent the various metabolic networks from phenylalanine ammonia lyase (PAL) to the monolignols were organized and/or could be predicted. In these databases, there are some 65 genes which have been annotated as encoding putative enzymatic steps in monolignol biosynthesis, although many of them have only very low homology to monolignol pathway genes of known function in other plant systems. Our detailed analysis revealed that presently only 13 genes (two PALs, a cinnamate-4-hydroxylase, a p-coumarate-3-hydroxylase, a ferulate-5-hydroxylase, three 4-coumarate-CoA ligases, a cinnamic acid O-methyl transferase, two cinnamoyl-CoA reductases) and two cinnamyl alcohol dehydrogenases can be classified as having a bona fide (definitive) function; the remaining 52 genes currently have undetermined physiological roles. The EST database entries for this particular set of genes also provided little new insight into how the monolignol pathway was organized in the different tissues and organs, this being perhaps a consequence of both limitations in how tissue samples were collected and in the incomplete nature of the EST collections. This analysis thus underscores the fact that even with genomic sequencing, presumed to provide the entire suite of putative genes in the monolignol-forming pathway, a very large effort needs to be conducted to establish actual catalytic roles (including enzyme versatility), as well as the physiological function(s) for each member

  20. Energy metabolism of synaptosomes from different neuronal systems of rat cerebellum during aging: a functional proteomic characterization.

    Ferrari, Federica; Gorini, Antonella; Villa, Roberto Federico

    2015-01-01

    Functional proteomics was used to characterize age-related changes in energy metabolism of different neuronal pathways within the cerebellar cortex of Wistar rats aged 2, 6, 12, 18, and 24 months. The "large" synaptosomes, derived from the glutamatergic mossy fibre endings which make synaptic contact with the granule cells of the granular layer, and the "small" synaptosomes, derived from the pre-synaptic terminals of granule cells making synaptic contact with the dendrites of Purkinje cells, were isolated by a combined differential/gradient centrifugation technique. Because most brain disorders are associated with bioenergetic changes, the maximum rate (Vmax) of selected enzymes of glycolysis, Krebs' cycle, glutamate and amino acids metabolism, and acetylcholine catabolism were evaluated. The results show that "large" and "small" synaptosomes possess specific and independent metabolic features. This study represents a reliable model to study in vivo (1) the physiopathological molecular mechanisms of some brain diseases dependent on energy metabolism, (2) the responsiveness to noxious stimuli, and (3) the effects of drugs, discriminating their action sites at subcellular level on specific neuronal pathways.

  1. Baroreflex function: determinants in healthy subjects and disturbances in diabetes, obesity and metabolic syndrome.

    Skrapari, Ioanna; Tentolouris, Nicholas; Katsilambros, Nicholas

    2006-08-01

    Arterial baroreceptors play an important role in the short-term regulation of arterial pressure, by reflex chronotropic effect on the heart and by reflex regulation of sympathetic outflow. Baroreflex sensitivity (BRS) represents an index of arterial baroreceptors function. Several methods of measuring BRS are available nowadays. Different factors influence BRS in the healthy population, including sex, age, blood pressure, heart rate, body fatness, arterial stiffness, blood glucose and insulin levels, as well as physical activity. Baroreceptors dysfunction is evident in diseases such as coronary artery disease, heart failure, arterial hypertension, diabetes mellitus and obesity. The underlying mechanism of BRS attenuation in diabetes or obesity is not yet well known; however, there is increasing evidence that it is at least partly related to autonomic nervous system dysfunction and particularly to sympathetic overactivity that accompanies these diseases. Blunted BRS provides prognostic information for cardiovascular diseases and possibly for diabetes, while its' prognostic information for obesity is not yet established. This review deals with the mechanisms affecting baroreflex function, the newer techniques of BRS estimation and the most recent insights of baroreflex function in the healthy population and in various diseases with emphasis on diabetes and obesity. In addition, the clinical implication of a reduced BRS in these disorders is discussed.

  2. Functional Effects of Prebiotic Fructans in Colon Cancer and Calcium Metabolism in Animal Models

    Rivera-Huerta, Marisol; Liz?rraga-Grimes, Vania Lorena; Castro-Torres, Ibrahim Guillermo; Tinoco-M?ndez, Mabel; Mac?as-Rosales, Luc?a; S?nchez-Bart?z, Francisco; Tapia-P?rez, Graciela Guadalupe; Romero-Romero, Laura; Gracia-Mora, Mar?a Isabel

    2017-01-01

    Inulin-type fructans are polymers of fructose molecules and are known for their capacity to enhance absorption of calcium and magnesium, to modulate gut microbiota and energy metabolism, and to improve glycemia. We evaluated and compared the effects of Chicory inulin “Synergy 1®” and inulin from Mexican agave “Metlin®” in two experimental models of colon cancer and bone calcium metabolism in mice and rats. Inulins inhibited the development of dextran sulfate sodium-induced colitis and colon c...

  3. Influence of abnormal glucose metabolism on coronary microvascular function after a recent myocardial infarction

    Løgstrup, Brian B; Høfsten, Dan E; Christophersen, Thomas B

    2009-01-01

    OBJECTIVES: This study sought to assess the association between abnormal glucose metabolism and abnormal coronary flow reserve (CFR) in patients with a recent acute myocardial infarction (AMI). BACKGROUND: Mortality and morbidity after AMI is high among patients with abnormal glucose metabolism, ...... (140 microg/kg/min) to obtain the hyperemic flow profiles. The CFR was defined as the ratio of hyperemic to baseline peak diastolic coronary flow velocities. RESULTS: Median CFR was 1.9 (interquartile range [IQR] 1.4 to 2.4], and 109 (60%) patients had a CFR...

  4. Title: Potassium application regulates nitrogen metabolism and osmotic adjustment in cotton (Gossypium hirsutum L.) functional leaf under drought stress.

    Zahoor, Rizwan; Zhao, Wenqing; Abid, Muhammad; Dong, Haoran; Zhou, Zhiguo

    2017-08-01

    To evaluate the role of potassium (K) in maintaining nitrogen metabolism and osmotic adjustment development of cotton functional leaves to sustain growth under soil drought and rewatering conditions, the plants of two cotton cultivars Siza 3 (low-K sensitive) and Simian 3 (low-K tolerant), were grown under three different K rates (K0, K1, and K2; 0, 150, and 300kgK 2 Oha -1 , respectively) and exposed to drought stress with 40±5% soil relative water content (SRWC). The drought stress was applied at flowering stage by withholding water for eight days followed by rewatering to a well-watered level (75±5% SRWC). The results showed that drought-stressed plants of both cultivars showed a decrease in leaf relative water content (RWC) and osmotic potential in the functional leaves and developed osmotic adjustment with an increase in the contents of free amino acids, soluble sugars, inorganic K, and nitrate as compared to well-watered plants. In drought-stressed plants, nitrogen-metabolizing enzyme activities of nitrogen reductase (NR), glutamine synthetase (GS), and glutamate synthase (GOGAT) were diminished significantly (P≤0.05) along with decreased chlorophyll content and soluble proteins. However, drought-stressed plants under K application not only exhibited higher osmotic adjustment with greater accumulation of osmolytes but also regulated nitrogen metabolism by maintaining higher enzyme activities, soluble proteins, and chlorophyll content in functional leaves as compared to the plants without K application. Siza 3 showed better stability in enzyme activities and resulted in 89% higher seed cotton yield under K2 as compared to K0 in drought-stressed plants, whereas this increase was 53% in the case of Simian 3. The results of the study suggested that K application enhances cotton plants' potential for sustaining high nitrogen-metabolizing enzyme activities and related components to supplement osmotic adjustment under soil drought conditions. Copyright © 2017

  5. Functions of NQO1 in Cellular Protection and CoQ10 Metabolism and its Potential Role as a Redox Sensitive Molecular Switch

    David Ross

    2017-08-01

    Full Text Available NQO1 is one of the two major quinone reductases in mammalian systems. It is highly inducible and plays multiple roles in cellular adaptation to stress. A prevalent polymorphic form of NQO1 results in an absence of NQO1 protein and activity so it is important to elucidate the specific cellular functions of NQO1. Established roles of NQO1 include its ability to prevent certain quinones from one electron redox cycling but its role in quinone detoxification is dependent on the redox stability of the hydroquinone generated by two-electron reduction. Other documented roles of NQO1 include its ability to function as a component of the plasma membrane redox system generating antioxidant forms of ubiquinone and vitamin E and at high levels, as a direct superoxide reductase. Emerging roles of NQO1 include its function as an efficient intracellular generator of NAD+ for enzymes including PARP and sirtuins which has gained particular attention with respect to metabolic syndrome. NQO1 interacts with a growing list of proteins, including intrinsically disordered proteins, protecting them from 20S proteasomal degradation. The interactions of NQO1 also extend to mRNA. Recent identification of NQO1 as a mRNA binding protein have been investigated in more detail using SERPIN1A1 (which encodes the serine protease inhibitor α-1-antitrypsin as a target mRNA and indicate a role of NQO1 in control of translation of α-1-antitrypsin, an important modulator of COPD and obesity related metabolic syndrome. NQO1 undergoes structural changes and alterations in its ability to bind other proteins as a result of the cellular reduced/oxidized pyridine nucleotide ratio. This suggests NQO1 may act as a cellular redox switch potentially altering its interactions with other proteins and mRNA as a result of the prevailing redox environment.

  6. Effects of inspiratory muscle exercise in the pulmonary function, autonomic modulation, and hemodynamic variables in older women with metabolic syndrome

    Feriani, Daniele Jardim; Coelho, Hélio José; Scapini, Kátia Bilhar; de Moraes, Oscar Albuquerque; Mostarda, Cristiano; Ruberti, Olivia Moraes; Uchida, Marco Carlos; Caperuto, Érico Chagas; Irigoyen, Maria Cláudia; Rodrigues, Bruno

    2017-01-01

    The aim of the present study was to investigate the effects of inspiratory muscle exercise (IME) on metabolic and hemodynamic parameters, cardiac autonomic modulation and respiratory function of older women with metabolic syndrome (MS). For this, sixteen older women with MS and 12 aged-matched controls participated of the present study. Two days before and 2 days after the main experiment, fasting blood samples (i.e., total cholesterol, triglycerides and blood glucose), cardiac autonomic modulation (i.e., heart rate variability), and respiratory muscle function were obtained and evaluated. The sessions of physical exercise was based on a IME, which was performed during 7 days. Each session of IME was performed during 20 min, at 30% of maximal static inspiratory pressure. In the results, MS group presented higher levels of triglycerides, blood glucose, and systolic blood pressure when compared to control group. IME was not able to change these variables. However, although MS group showed impaired respiratory muscle strength and function, as well as cardiac autonomic modulation, IME was able to improve these parameters. Thus, the data showed that seven days of IME are capable to improve respiratory function and cardiac autonomic modulation of older women with MS. These results indicate that IME can be a profitable therapy to counteracting the clinical markers of MS, once repeated sessions of acute IME can cause chronical alterations on respiratory function and cardiac autonomic modulation. PMID:28503537

  7. Metabolic engineering of deinococcus radiodurans based on computational analysis and functional genomics

    Edwards, Jeremy, S.

    2005-02-02

    The objective of our work is to develop novel computational tools to analyze the Deinococcus radiodurans DNA repair pathways and the influence of the metabolic flux distribution on DNA repair. These tools will be applied to provide insights for metabolic engineering of strains capable of growing under nutrient poor conditions similar to those found in mixed contaminant sites of interest to the DOE. Over the entire grant period we accomplished all our specific aims and were also able to pursue new directions of research. Below, I will list the major accomplishments over the previous 3 years. (1) Performed Monte Carlo Simulations of RecA Mediated Pairing of Homologous DNA Molecules. (2) Developed a statistical approach to study the gene expression data from D. radiodurans. We have been studying the data from John Batista's. (3) Developed an expression profiling technology to generate very accurate and precise expression data. We followed up on results from John Batista's group using this approach. (4) Developed and put online a database for metabolic reconstructions. (5) We have developed and applied new Monte Carlo algorithms that are optimized for studying biological systems. (6) We developed a flux balance model for the D. radiodurans metabolic network

  8. Reconstructing phylogeny by aligning multiple metabolic pathways using functional module mapping

    Huang, Yiran; Zhong, Cheng; Lin, H.X.; Wang, Jianyi; Peng, Yuzhong

    2018-01-01

    Comparison of metabolic pathways provides a systematic way for understanding the evolutionary and phylogenetic relationships in systems biology. Although a number of phylogenetic methods have been developed, few efforts have been made to provide a unified phylogenetic framework that sufficiently

  9. Resveratrol Is Not as Effective as Physical Exercise for Improving Reproductive and Metabolic Functions in Rats with Dihydrotestosterone-Induced Polycystic Ovary Syndrome

    Anna Benrick

    2013-01-01

    Full Text Available Polycystic ovary syndrome (PCOS is a reproductive and metabolic disorder associated with obesity and insulin resistance that often precedes the development of type-2 diabetes. Rats continuously exposed to dihydrotestosterone from prepuberty display typical reproductive and metabolic PCOS characteristics including anovulation, polycystic ovaries, insulin resistance, and obesity. Our aim was to investigate if resveratrol improves reproductive and metabolic functions in PCOS rats. The effect was compared to exercise. Control and PCOS rats were treated with vehicle or resveratrol (400 mg · kg−1 · day−1 for 5-6 weeks. Another group of PCOS rats received vehicle treatment and exercised for 5-6 weeks. Insulin sensitivity was determined by euglycemic-hyperinsulinemic clamp. The glucose infusion rate was lower in the PCOS-vehicle group compared to control-vehicle rats (P<0.05. Exercise increased insulin sensitivity compared with PCOS-vehicle rats (P<0.05, but resveratrol did not. Resveratrol treatment and exercise resulted in smaller adipocytes, upregulated estrogen-related receptor α gene expression in subcutaneous fat, and improved estrus cyclicity in the previously acyclic PCOS rats. Although resveratrol had positive effects on adiposity and cyclicity in a similar manner to exercise, resveratrol does not seem to be a good candidate for treating insulin resistance associated with PCOS because no improvement in insulin sensitivity was observed in PCOS rats on normal chow.

  10. Differential Reliance on Lipid Metabolism as a Salvage Pathway Underlies Functional Differences of T Cell Subsets in Poor Nutrient Environments

    Christopher Ecker

    2018-04-01

    Full Text Available Summary: T cells compete with malignant cells for limited nutrients within the solid tumor microenvironment. We found that effector memory CD4 T cells respond distinctly from other T cell subsets to limiting glucose and can maintain high levels of interferon-γ (IFN-γ production in a nutrient-poor environment. Unlike naive (TN or central memory T (TCM cells, effector memory T (TEM cells fail to upregulate fatty acid synthesis, oxidative phosphorylation, and reductive glutaminolysis in limiting glucose. Interference of fatty acid synthesis in naive T cells dramatically upregulates IFN-γ, while increasing exogenous lipids in media inhibits production of IFN-γ by all subsets, suggesting that relative ratio of fatty acid metabolism to glycolysis is a direct predictor of T cell effector activity. Together, these data suggest that effector memory T cells are programmed to have limited ability to synthesize and metabolize fatty acids, which allows them to maintain T cell function in nutrient-depleted microenvironments. : Ecker et al. distinguish unique metabolic and functional properties of naive and memory T cell subsets during glucose limitation. During glucose starvation, T cells begin to differentially rely on fatty acid synthesis and glutamine utilization to survive. Unexpectedly, reliance on fatty acid synthesis alters the ability to produce IFN-γ. Keywords: lipid droplets, IFN-γ, oxidative phosphorylation, reductive glutaminolysis, serum-free media, naive T cell, glycolysis, effector memory T cell, fatty acid synthesis

  11. Phylogenetic and functional analysis of metagenome sequence from high-temperature archaeal habitats demonstrate linkages between metabolic potential and geochemistry

    William P. Inskeep

    2013-05-01

    Full Text Available Geothermal habitats in Yellowstone National Park (YNP provide an unparalled opportunity to understand the environmental factors that control the distribution of archaea in thermal habitats. Here we describe, analyze and synthesize metagenomic and geochemical data collected from seven high-temperature sites that contain microbial communities dominated by archaea relative to bacteria. The specific objectives of the study were to use metagenome sequencing to determine the structure and functional capacity of thermophilic archaeal-dominated microbial communities across a pH range from 2.5 to 6.4 and to discuss specific examples where the metabolic potential correlated with measured environmental parameters and geochemical processes occurring in situ. Random shotgun metagenome sequence (~40-45 Mbase Sanger sequencing per site was obtained from environmental DNA extracted from high-temperature sediments and/or microbial mats and subjected to numerous phylogenetic and functional analyses. Analysis of individual sequences (e.g., MEGAN and G+C content and assemblies from each habitat type revealed the presence of dominant archaeal populations in all environments, 10 of whose genomes were largely reconstructed from the sequence data. Analysis of protein family occurrence, particularly of those involved in energy conservation, electron transport and autotrophic metabolism, revealed significant differences in metabolic strategies across sites consistent with differences in major geochemical attributes (e.g., sulfide, oxygen, pH. These observations provide an ecological basis for understanding the distribution of indigenous archaeal lineages across high temperature systems of YNP.

  12. Basal Forebrain Cholinergic Deficits Reduce Glucose Metabolism and Function of Cholinergic and GABAergic Systems in the Cingulate Cortex.

    Jeong, Da Un; Oh, Jin Hwan; Lee, Ji Eun; Lee, Jihyeon; Cho, Zang Hee; Chang, Jin Woo; Chang, Won Seok

    2016-01-01

    Reduced brain glucose metabolism and basal forebrain cholinergic neuron degeneration are common features of Alzheimer's disease and have been correlated with memory function. Although regions representing glucose hypometabolism in patients with Alzheimer's disease are targets of cholinergic basal forebrain neurons, the interaction between cholinergic denervation and glucose hypometabolism is still unclear. The aim of the present study was to evaluate glucose metabolism changes caused by cholinergic deficits. We lesioned basal forebrain cholinergic neurons in rats using 192 immunoglobulin G-saporin. After 3 weeks, lesioned animals underwent water maze testing or were analyzed by ¹⁸F-2-fluoro-2-deoxyglucose positron emission tomography. During water maze probe testing, performance of the lesioned group decreased with respect to time spent in the target quadrant and platform zone. Cingulate cortex glucose metabolism in the lesioned group decreased, compared with the normal group. Additionally, acetylcholinesterase activity and glutamate decarboxylase 65/67 expression declined in the cingulate cortex. Our results reveal that spatial memory impairment in animals with selective basal forebrain cholinergic neuron damage is associated with a functional decline in the GABAergic and cholinergic system associated with cingulate cortex glucose hypometabolism.

  13. Combinatorial function of velvet and AreA in transcriptional regulation of nitrate utilization and secondary metabolism.

    López-Berges, Manuel S; Schäfer, Katja; Hera, Concepción; Di Pietro, Antonio

    2014-01-01

    Velvet is a conserved protein complex that functions as a regulator of fungal development and secondary metabolism. In the soil-inhabiting pathogen Fusarium oxysporum, velvet governs mycotoxin production and virulence on plant and mammalian hosts. Here we report a previously unrecognized role of the velvet complex in regulation of nitrate metabolism. F. oxysporum mutants lacking VeA or LaeA, two key components of the complex, were impaired in growth on the non-preferred nitrogen sources nitrate and nitrite. Both velvet and the general nitrogen response GATA factor AreA were required for transcriptional activation of nitrate (nit1) and nitrite (nii1) reductase genes under de-repressing conditions, as well as for the nitrate-triggered increase in chromatin accessibility at the nit1 locus. AreA also contributed to chromatin accessibility and expression of two velvet-regulated gene clusters, encoding biosynthesis of the mycotoxin beauvericin and of the siderophore ferricrocin. Thus, velvet and AreA coordinately orchestrate primary and secondary metabolism as well as virulence functions in F. oxysporum. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Natural products, an important resource for discovery of multitarget drugs and functional food for regulation of hepatic glucose metabolism.

    Li, Jian; Yu, Haiyang; Wang, Sijian; Wang, Wei; Chen, Qian; Ma, Yanmin; Zhang, Yi; Wang, Tao

    2018-01-01

    Imbalanced hepatic glucose homeostasis is one of the critical pathologic events in the development of metabolic syndromes (MSs). Therefore, regulation of imbalanced hepatic glucose homeostasis is important in drug development for MS treatment. In this review, we discuss the major targets that regulate hepatic glucose homeostasis in human physiologic and pathophysiologic processes, involving hepatic glucose uptake, glycolysis and glycogen synthesis, and summarize their changes in MSs. Recent literature suggests the necessity of multitarget drugs in the management of MS disorder for regulation of imbalanced glucose homeostasis in both experimental models and MS patients. Here, we highlight the potential bioactive compounds from natural products with medicinal or health care values, and focus on polypharmacologic and multitarget natural products with effects on various signaling pathways in hepatic glucose metabolism. This review shows the advantage and feasibility of discovering multicompound-multitarget drugs from natural products, and providing a new perspective of ways on drug and functional food development for MSs.

  15. Identification of differences in human and great ape phytanic acid metabolism that could influence gene expression profiles and physiological functions

    Siegmund Kimberly D

    2010-10-01

    Full Text Available Abstract Background It has been proposed that anatomical differences in human and great ape guts arose in response to species-specific diets and energy demands. To investigate functional genomic consequences of these differences, we compared their physiological levels of phytanic acid, a branched chain fatty acid that can be derived from the microbial degradation of chlorophyll in ruminant guts. Humans who accumulate large stores of phytanic acid commonly develop cerebellar ataxia, peripheral polyneuropathy, and retinitis pigmentosa in addition to other medical conditions. Furthermore, phytanic acid is an activator of the PPAR-alpha transcription factor that influences the expression of genes relevant to lipid metabolism. Results Despite their trace dietary phytanic acid intake, all great ape species had elevated red blood cell (RBC phytanic acid levels relative to humans on diverse diets. Unlike humans, chimpanzees showed sexual dimorphism in RBC phytanic acid levels, which were higher in males relative to females. Cultured skin fibroblasts from all species had a robust capacity to degrade phytanic acid. We provide indirect evidence that great apes, in contrast to humans, derive significant amounts of phytanic acid from the hindgut fermentation of plant materials. This would represent a novel reduction of metabolic activity in humans relative to the great apes. Conclusion We identified differences in the physiological levels of phytanic acid in humans and great apes and propose this is causally related to their gut anatomies and microbiomes. Phytanic acid levels could contribute to cross-species and sex-specific differences in human and great ape transcriptomes, especially those related to lipid metabolism. Based on the medical conditions caused by phytanic acid accumulation, we suggest that differences in phytanic acid metabolism could influence the functions of human and great ape nervous, cardiovascular, and skeletal systems.

  16. Effect of STA-proximal MCA bypass. Improvement of cerebral blood flow and metabolism and neuropsychological function

    Ogawa, Akira; Funayama, Masayuki; Miura, Kazuyuki; Ogasawara, Kuniaki; Suzuki, Michiyasu; Kuroda, Kiyoshi; Sasaki, Toshiaki

    1998-01-01

    We investigated cerebral blood flow (CBF) and metabolism in patients with hemodynamic ischemia by positron emission tomography (PET) and thermal diffusion flow meter. We also studied neuropsychological functions to evaluate the effects of surgical revascularization. Bypass surgery of the superficial temporal artery to the proximal middle cerebral artery was performed on 26 patients satisfying the following categories: stenosis or occlusive lesion in main cerebral arteries; no marked focus of infarction on CT or MRI. PET was performed before and 1 month after the operation, and CBF, the cerebral metabolic rate of oxygen (CMRO 2 ) and oxygen extraction fraction (OEF) were analyzed. Cerebrovascular reserve capacity (CVRC) was also calculated after acetazolamide challenge. CBF during the operation was continuously measured with a thermal diffusion flow meter. CO 2 response of CBF was analyzed before and after anastomosis. Neuropsychological functions were evaluated by Hasegawa dementia scale revised (HDS-R), mini-mental state examination (MMSE) and Wechsler adult intelligence scale revised (WAIS-R). Before the operation, increase in OEF accorded with the decrease in CBF, and a significant relationship between both CBF and CVRC, and OEF and CVRC was found. A decrease in CVRC was noted prior to a decrease in CBF and elevation of OEF. CVRC caused by acetazolamide might reflect CO 2 reactivity. Significant improvement of CBF and CVRC, and normalization of OEF were observed after the operation. Also, significant improvement of neuropsychological function was observed by HDS-R and WAIS-R. Disturbance in neuropsychological function might reflect elevation of OEF. (author)

  17. Health effects of an increased protein intake on kidney function and colorectal cancer risk factors, including the role of animal and plant protein sources – the PREVIEW project

    Møller, Grith

    intake, including the role of animal and plant protein in pre-diabetic, overweight or obese individuals on health outcomes: markers of kidney function and putative risk factors for colorectal cancer as well as insulin sensitivity and kidney function in healthy individuals. The thesis is based on PREVIEW......, especially plant protein, on insulin sensitivity and kidney function. In paper II, the aim of the study was to assess the effect after one year of a higher protein intake on kidney function, measured by in creatinine clearance. This was investigated in pre-diabetic older adults based on a sub-group of 310...... pre-diabetic individuals included in the PREVIEW RCT. We found that a higher protein intake was associated with a significant increase in urea to creatinine ratio and serum urea after one year. There were no associations between increased protein intake and creatinine clearance, estimated glomerular...

  18. Pancreatic cancerrelated cachexia: influence on metabolism and correlation to weight loss and pulmonary function

    Bachmann, Jeannine; Ketterer, Knut; Marsch, Christiane; Fechtner, Kerstin; Krakowski-Roosen, Holger; Büchler, Markus W; Friess, Helmut; Martignoni, Marc E

    2009-01-01

    Dramatic weight loss is an often underestimated symptom in pancreatic cancer patients. Cachexia- defined as an unintended loss of stable weight exceeding 10% – is present in up to 80% of patients with cancer of the upper gastrointestinal tract, and has a significant influence on survival. The aim of the study was to show the multiple systemic effects of cachexia in pancreatic cancer patients, in terms of resection rate, effects on pulmonary function, amount of fat and muscle tissue, as well as changes in laboratory parameters. In patients with pancreatic cancer, clinical appearance was documented, including the amount of weight loss. Laboratory parameters and lung-function tests were evaluated, and the thickness of muscle and fat tissue was measured with computed tomography scans. Statistical analysis, including multivariate analysis, was performed using SPSS software. Survival curves were calculated using Kaplan-Meier analysis and the log-rank test. To test for significant differences between the examined groups we used Student's t-test and the Mann-Whitney U test. Significance was defined as p < 0.05. Of 198 patients with a ductal adenocarcinoma of the pancreas, 70% were suffering from weight loss when they presented for operation, and in 40% weight loss exceeded 10% of the stable weight. In patients with cachexia, metastases were diagnosed significantly more often (47% vs. 24%, P < 0.001), leading to a significantly reduced resection rate in these patients. Patients with cachexia had significantly reduced fat tissue amounts. Hence, dramatic weight loss in a patient with pancreatic cancer may be a hint of a more progressed or more aggressive tumour. Pancreatic cancer patients with cachexia had a higher rate of more progressed tumour stages and a worse nutritional status. Furthermore, patients with cachexia had an impaired lung function and a reduction in fat tissue. Patients with pancreatic cancer and cachexia had significantly reduced survival. If weight

  19. Pancreatic cancerrelated cachexia: influence on metabolism and correlation to weight loss and pulmonary function

    Bachmann, Jeannine; Ketterer, Knut [Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Munich (Germany); Marsch, Christiane [Department of General Surgery, University of Heidelberg, Heidelberg (Germany); Fechtner, Kerstin [Department of Radiology, University of Heidelberg, Heidelberg (Germany); Krakowski-Roosen, Holger [German Cancer Research Center, Heidelberg (Germany); Büchler, Markus W [Department of General Surgery, University of Heidelberg, Heidelberg (Germany); Friess, Helmut; Martignoni, Marc E [Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Munich (Germany)

    2009-07-28

    Dramatic weight loss is an often underestimated symptom in pancreatic cancer patients. Cachexia- defined as an unintended loss of stable weight exceeding 10% – is present in up to 80% of patients with cancer of the upper gastrointestinal tract, and has a significant influence on survival. The aim of the study was to show the multiple systemic effects of cachexia in pancreatic cancer patients, in terms of resection rate, effects on pulmonary function, amount of fat and muscle tissue, as well as changes in laboratory parameters. In patients with pancreatic cancer, clinical appearance was documented, including the amount of weight loss. Laboratory parameters and lung-function tests were evaluated, and the thickness of muscle and fat tissue was measured with computed tomography scans. Statistical analysis, including multivariate analysis, was performed using SPSS software. Survival curves were calculated using Kaplan-Meier analysis and the log-rank test. To test for significant differences between the examined groups we used Student's t-test and the Mann-Whitney U test. Significance was defined as p < 0.05. Of 198 patients with a ductal adenocarcinoma of the pancreas, 70% were suffering from weight loss when they presented for operation, and in 40% weight loss exceeded 10% of the stable weight. In patients with cachexia, metastases were diagnosed significantly more often (47% vs. 24%, P < 0.001), leading to a significantly reduced resection rate in these patients. Patients with cachexia had significantly reduced fat tissue amounts. Hence, dramatic weight loss in a patient with pancreatic cancer may be a hint of a more progressed or more aggressive tumour. Pancreatic cancer patients with cachexia had a higher rate of more progressed tumour stages and a worse nutritional status. Furthermore, patients with cachexia had an impaired lung function and a reduction in fat tissue. Patients with pancreatic cancer and cachexia had significantly reduced survival. If weight loss

  20. Negative Impact of Testosterone Deficiency and 5α-Reductase Inhibitors Therapy on Metabolic and Sexual Function in Men.

    Traish, Abdulmaged M

    2017-01-01

    Androgens are steroid hormones with pleotropic and diverse biochemical and physiological functions, and androgen deficiency exerts a negative impact on human health. Testosterone (T) either directly or via its transformation into the more potent metabolite 5α-dihydrotestosterone (5α-DHT) or via aromatization into estradiol (E 2 ) modulates important biochemical signaling pathways of human physiology and plays a critical role in the growth and/or maintenance of functions in a host of tissues and organs. T and 5α-DHT play an important role in regulating physiology of the muscle, adipose tissue, liver, bone, and central nervous system, as well as reproductive and sexual functions. Thus, androgen deficiency (also referred to as hypogonadism) is a well-recognized medical condition and if remained untreated will have a negative impact on human health and quality of life.In this chapter, we have summarized the negative impact of T deficiency (TD) on a host of physiological functions including reduced lean body mass (LBM), increased fat mass (FM), increased insulin resistance (IR), metabolic syndrome (MetS) and adiposity, reduced bone mineral density (BMD), anemia, sexual dysfunction, and reduced quality of life and increased mortality. In addition, we discuss another critical aspect of unrecognized form of androgen deficiency resulting from inhibition of 5α-reductases with drugs, such as finasteride and dutasteride, to block transformation of T into 5α-DHT in the course of treatment of benign prostatic hyperplasia (BPH) and male pattern hair loss, also known as androgenetic alopecia (AGA). The negative impact of drugs that inhibit transformation of T to 5α-DHT by 5α-reductases on metabolic function is manifested in fat accumulation in the liver, which may predispose to nonalcoholic fatty liver disease (NAFLD). Also, inhibition of 5α-DHT formation increases glucose synthesis and reduces glucose disposal potentially contributing to hyperglycemia, IR, and

  1. Glucocorticoid receptor action in metabolic and neuronal function [version 1; referees: 3 approved

    Michael J. Garabedian

    2017-07-01

    Full Text Available Glucocorticoids via the glucocorticoid receptor (GR have effects on a variety of cell types, eliciting important physiological responses via changes in gene expression and signaling. Although decades of research have illuminated the mechanism of how this important steroid receptor controls gene expression using in vitro and cell culture–based approaches, how GR responds to changes in external signals in vivo under normal and pathological conditions remains elusive. The goal of this review is to highlight recent work on GR action in fat cells and liver to affect metabolism in vivo and the role GR ligands and receptor phosphorylation play in calibrating signaling outputs by GR in the brain in health and disease. We also suggest that both the brain and fat tissue communicate to affect physiology and behavior and that understanding this “brain-fat axis” will enable a more complete understanding of metabolic diseases and inform new ways to target them.

  2. How tyrosine kinase inhibitors impair metabolism and endocrine system function: a systematic updated review.

    Breccia, Massimo; Molica, Matteo; Alimena, Giuliana

    2014-12-01

    Tyrosine kinase inhibitors (TKIs) advent has deeply changed the outcome of chronic myeloid leukemia (CML) patients, with improved rates of response and overall survival. However, for this success some patients paid the price of a number of peculiar side effects, the so-called off-target side effects, specific for each one TKI. These effects are due to non-selective inhibition of other tyrosine kinase receptors, such as PDGFR, c-KIT, Src, VEGF. Consequences of this inhibition, some metabolic changes during the treatment with TKIs are reported. Aim of present review is to report metabolic changes and potential mechanisms involved in the pathogenesis related to imatinib, second (nilotinib and dasatinib) and third generation (bosutinib and ponatinib) TKIs. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Brain energy metabolism and dopaminergic function in Huntington's disease measured in vivo using positron emission tomography

    Leenders, K.L.; Frackowiak, R.S.; Quinn, N.; Marsden, C.D.

    1986-01-01

    A 48-year-old man with typical Huntington's disease was investigated with computed tomography (CT) and positron emission tomography. Regional cerebral blood flow, oxygen extraction, oxygen and glucose utilization, L-Dopa uptake, and dopamine (D2) receptor binding were measured using several positron-labelled tracers. CT showed slight atrophy of the head of caudate but no cortical atrophy, although distinct frontal lobe dysfunction was present on psychometric testing. Oxygen and glucose metabolism and cerebral blood flow were decreased in the striata and to a lesser extent in frontal cortex. Cerebral blood flow was in the low normal range throughout the remainder of the brain. A normal metabolic ratio was found in all regions, since the changes in glucose utilization paralleled those in oxygen consumption. The capacity of the striatum to store dopamine as assessed by L-[ 18 F]-fluorodopa uptake was normal, but dopamine (D2) receptor binding was decreased when compared to normal subjects

  4. Application of compartmental metabolic models for determination of retention and excretion functions

    Rodrigues Junior, O.

    1994-01-01

    After an intake of radioactive material, its behaviour in the human body can be described by mathematical models, where organs, tissues or regions of the body are treated as a chain of linked compartments. The mathematical approach for such metabolic models is usually done through a system of differential equations of first order with constant coefficients. The solutions of this system of equations associates the radionuclide intake, with the fraction excreted or retained in the organ of interest. A computer program - called INCORP and for running in PC compatible microcomputers - was developed in order to find the solutions of such system of equations, using an analytical method based on expansion of series of exponential matrices. The metabolic model presented in the ICRP-30 publication was simulated using the INCORP program, in order to find the respective retention and excretion curves for selected radionuclides. (author)

  5. Amiodarone: Effects on thyroid function and the peripheral metabolism of the thyroid hormones

    Braverman, L.E.; Safran, M.; Bambini, G.; Pinchera, A.; Martino, E.

    1985-01-01

    In addition to the effects of Amiodarone on the peripheral metabolism of the thyroid hormones and on pituitary TSH secretion, a major complication of therapy is the relatively high frequency of iodide-induced thyroid dysfunction. The mean T 4 and T 3 concentration following Amiodarone application was measured in euthyroid, hypothyroid and hyperthyroid patients and in control patients with and without cardiac disorders. Furthermore, the serum TSH was determined in euthyroid Amiodarone-treated euthyroid patients. 131 I uptake was studied in patients with Amiodarone-associated thyrotoxicosis. The difficulties of the therapy of Amiodarone-induced hyper-thyroidism are outlined. Preliminary studied of the effect of Amiodarone and its analogues on the metabolism of thyroid hormones in the rat indicate that Amiodarone may act as a thyroid hormone agonist in the pituitary. (MG)

  6. Cyclin G Functions as a Positive Regulator of Growth and Metabolism in Drosophila.

    Patrick Fischer

    2015-08-01

    Full Text Available In multicellular organisms, growth and proliferation is adjusted to nutritional conditions by a complex signaling network. The Insulin receptor/target of rapamycin (InR/TOR signaling cascade plays a pivotal role in nutrient dependent growth regulation in Drosophila and mammals alike. Here we identify Cyclin G (CycG as a regulator of growth and metabolism in Drosophila. CycG mutants have a reduced body size and weight and show signs of starvation accompanied by a disturbed fat metabolism. InR/TOR signaling activity is impaired in cycG mutants, combined with a reduced phosphorylation status of the kinase Akt1 and the downstream factors S6-kinase and eukaryotic translation initiation factor 4E binding protein (4E-BP. Moreover, the expression and accumulation of Drosophila insulin like peptides (dILPs is disturbed in cycG mutant brains. Using a reporter assay, we show that the activity of one of the first effectors of InR signaling, Phosphoinositide 3-kinase (PI3K92E, is unaffected in cycG mutants. However, the metabolic defects and weight loss in cycG mutants were rescued by overexpression of Akt1 specifically in the fat body and by mutants in widerborst (wdb, the B'-subunit of the phosphatase PP2A, known to downregulate Akt1 by dephosphorylation. Together, our data suggest that CycG acts at the level of Akt1 to regulate growth and metabolism via PP2A in Drosophila.

  7. Novel metabolic and physiological functions of branched chain amino acids: a review

    Zhang, Shihai; Zeng, Xiangfang; Ren, Man; Mao, Xiangbing; Qiao, Shiyan

    2017-01-01

    It is widely known that branched chain amino acids (BCAA) are not only elementary components for building muscle tissue but also participate in increasing protein synthesis in animals and humans. BCAA (isoleucine, leucine and valine) regulate many key signaling pathways, the most classic of which is the activation of the mTOR signaling pathway. This signaling pathway connects many diverse physiological and metabolic roles. Recent years have witnessed many striking developments in determining ...

  8. Model-driven discovery of underground metabolic functions in Escherichia coli

    Guzmán, Gabriela I.; Utrilla, José; Nurk, Sergey

    2015-01-01

    -scale models, which have been widely used for predicting growth phenotypes in various environments or following a genetic perturbation; however, these predictions occasionally fail. Failed predictions of gene essentiality offer an opportunity for targeting biological discovery, suggesting the presence......E, and gltA and prpC. This study demonstrates how a targeted model-driven approach to discovery can systematically fill knowledge gaps, characterize underground metabolism, and elucidate regulatory mechanisms of adaptation in response to gene KO perturbations....

  9. An AICD-based functional screen to identify APP metabolism regulators

    Lee Jeremy C

    2007-08-01

    Full Text Available Abstract Background A central event in Alzheimer's disease (AD is the regulated intramembraneous proteolysis of the β-amyloid precursor protein (APP, to generate the β-amyloid (Aβ peptide and the APP intracellular domain (AICD. Aβ is the major component of amyloid plaques and AICD displays transcriptional activation properties. We have taken advantage of AICD transactivation properties to develop a genetic screen to identify regulators of APP metabolism. This screen relies on an APP-Gal4 fusion protein, which upon normal proteolysis, produces AICD-Gal4. Production of AICD-Gal4 induces Gal4-UAS driven luciferase expression. Therefore, when regulators of APP metabolism are modulated, luciferase expression is altered. Results To validate this experimental approach we modulated α-, β-, and γ-secretase levels and activities. Changes in AICD-Gal4 levels as measured by Western blot analysis were strongly and significantly correlated to the observed changes in AICD-Gal4 mediated luciferase activity. To determine if a known regulator of APP trafficking/maturation and Presenilin1 endoproteolysis could be detected using the AICD-Gal4 mediated luciferase assay, we knocked-down Ubiquilin 1 and observed decreased luciferase activity. We confirmed that Ubiquilin 1 modulated AICD-Gal4 levels by Western blot analysis and also observed that Ubiquilin 1 modulated total APP levels, the ratio of mature to immature APP, as well as PS1 endoproteolysis. Conclusion Taken together, we have shown that this screen can identify known APP metabolism regulators that control proteolysis, intracellular trafficking, maturation and levels of APP and its proteolytic products. We demonstrate for the first time that Ubiquilin 1 regulates APP metabolism in the human neuroblastoma cell line, SH-SY5Y.

  10. The Global Regulator Spx Functions in the Control of Organosulfur Metabolism in Bacillus subtilis†

    Choi, Soon-Yong; Reyes, Dindo; Leelakriangsak, Montira; Zuber, Peter

    2006-01-01

    Spx is a global transcriptional regulator of the oxidative stress response in Bacillus subtilis. Its target is RNA polymerase, where it contacts the α subunit C-terminal domain. Recently, evidence was presented that Spx participates in sulfate-dependent control of organosulfur utilization operons, including the ytmI, yxeI, ssu, and yrrT operons. The yrrT operon includes the genes that function in cysteine synthesis from S-adenosylmethionine through intermediates S-adenosylhomocysteine, ribosylhomocysteine, homocysteine, and cystathionine. These operons are also negatively controlled by CymR, the repressor of cysteine biosynthesis operons. All of the operons are repressed in media containing cysteine or sulfate but are derepressed in medium containing the alternative sulfur source, methionine. Spx was found to negatively control the expression of these operons in sulfate medium, in part, by stimulating the expression of the cymR gene. In addition, microarray analysis, monitoring of yrrT-lacZ fusion expression, and in vitro transcription studies indicate that Spx directly activates yrrT operon expression during growth in medium containing methionine as sole sulfur source. These experiments have uncovered additional roles for Spx in the control of gene expression during unperturbed, steady-state growth. PMID:16885442

  11. Developmental Programming in Response to Intrauterine Growth Restriction Impairs Myoblast Function and Skeletal Muscle Metabolism

    Yates, D. T.; Macko, A. R.; Nearing, M.; Chen, X.; Rhoads, R. P.; Limesand, S. W.

    2012-01-01

    Fetal adaptations to placental insufficiency alter postnatal metabolic homeostasis in skeletal muscle by reducing glucose oxidation rates, impairing insulin action, and lowering the proportion of oxidative fibers. In animal models of intrauterine growth restriction (IUGR), skeletal muscle fibers have less myonuclei at birth. This means that myoblasts, the sole source for myonuclei accumulation in fibers, are compromised. Fetal hypoglycemia and hypoxemia are complications that result from placental insufficiency. Hypoxemia elevates circulating catecholamines, and chronic hypercatecholaminemia has been shown to reduce fetal muscle development and growth. We have found evidence for adaptations in adrenergic receptor expression profiles in myoblasts and skeletal muscle of IUGR sheep fetuses with placental insufficiency. The relationship of β-adrenergic receptors shifts in IUGR fetuses because Adrβ2 expression levels decline and Adrβ1 expression levels are unaffected in myofibers and increased in myoblasts. This adaptive response would suppress insulin signaling, myoblast incorporation, fiber hypertrophy, and glucose oxidation. Furthermore, this β-adrenergic receptor expression profile persists for at least the first month in IUGR lambs and lowers their fatty acid mobilization. Developmental programming of skeletal muscle adrenergic receptors partially explains metabolic and endocrine differences in IUGR offspring, and the impact on metabolism may result in differential nutrient utilization. PMID:22900186

  12. Developmental Programming in Response to Intrauterine Growth Restriction Impairs Myoblast Function and Skeletal Muscle Metabolism

    D. T. Yates

    2012-01-01

    Full Text Available Fetal adaptations to placental insufficiency alter postnatal metabolic homeostasis in skeletal muscle by reducing glucose oxidation rates, impairing insulin action, and lowering the proportion of oxidative fibers. In animal models of intrauterine growth restriction (IUGR, skeletal muscle fibers have less myonuclei at birth. This means that myoblasts, the sole source for myonuclei accumulation in fibers, are compromised. Fetal hypoglycemia and hypoxemia are complications that result from placental insufficiency. Hypoxemia elevates circulating catecholamines, and chronic hypercatecholaminemia has been shown to reduce fetal muscle development and growth. We have found evidence for adaptations in adrenergic receptor expression profiles in myoblasts and skeletal muscle of IUGR sheep fetuses with placental insufficiency. The relationship of β-adrenergic receptors shifts in IUGR fetuses because Adrβ2 expression levels decline and Adrβ1 expression levels are unaffected in myofibers and increased in myoblasts. This adaptive response would suppress insulin signaling, myoblast incorporation, fiber hypertrophy, and glucose oxidation. Furthermore, this β-adrenergic receptor expression profile persists for at least the first month in IUGR lambs and lowers their fatty acid mobilization. Developmental programming of skeletal muscle adrenergic receptors partially explains metabolic and endocrine differences in IUGR offspring, and the impact on metabolism may result in differential nutrient utilization.

  13. Distinct brain metabolic patterns separately associated with cognition, motor function, and aging in Parkinson's disease dementia.

    Ko, Ji Hyun; Katako, Audrey; Aljuaid, Maram; Goertzen, Andrew L; Borys, Andrew; Hobson, Douglas E; Kim, Seok Min; Lee, Chong Sik

    2017-12-01

    We explored whether patients with Parkinson's disease dementia (PDD) show a distinct spatial metabolic pattern that characterizes cognitive deficits in addition to motor dysfunction. Eighteen patients with PDD underwent 3 separate positron emission tomography sessions with [ 18 F]fluorodeoxyglucose (for glucose metabolism), fluorinated N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane (for dopamine transporter density) and Pittsburgh compound-B (for beta-amyloid load). We confirmed in PDD versus normal controls, overall hypometabolism in the posterior and prefrontal brain regions accompanied with hypermetabolism in subcortical structures and the cerebellar vermis. A multivariate network analysis then revealed 3 metabolic patterns that are separately associated with cognitive performance (p = 0.042), age (p = 0.042), and motor symptom severity (p = 0.039). The age-related pattern's association with aging was replicated in healthy controls (p = 0.047) and patients with Alzheimer's disease (p = 0.002). The cognition-related pattern's association with cognitive performance was observed, with a trend-level of correlation, in patients with dementia with Lewy bodies (p = 0.084) but not in patients with Alzheimer's disease (p = 0.974). We found no association with fluorinated N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane and Pittsburgh compound-B positron emission tomography with patients' cognitive performance. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. The in utero programming effect of increased maternal androgens and a direct fetal intervention on liver and metabolic function in adult sheep.

    Kirsten Hogg

    Full Text Available Epigenetic changes in response to external stimuli are fast emerging as common underlying causes for the pre-disposition to adult disease. Prenatal androgenization is one such model that results in reproductive and metabolic features that are present in conditions such as polycystic ovary syndrome (PCOS. We examined the effect of prenatal androgens on liver function and metabolism of adult sheep. As non-alcoholic fatty liver disease is increased in PCOS we hypothesized that this, and other important liver pathways including metabolic function, insulin-like growth factor (IGF and steroid receptivity, would be affected. Pregnant ewes received vehicle control (C; n = 5 or testosterone propionate (TP; n = 9 twice weekly (100 mg; i.m from d62-102 (gestation 147 days. In a novel treatment paradigm, a second cohort received a direct C (n = 4 or TP (20 mg; n = 7 fetal injection at d62 and d82. In adults, maternal TP exposure resulted in increased insulin secretion to glucose load (P<0.05 and the histological presence of fatty liver (P<0.05 independent of central obesity. Additionally, hepatic androgen receptor (AR; P<0.05, glucocorticoid receptor (GR; P<0.05, UDP- glucose ceramide glucosyltransferase (UGCG; P<0.05 and IGF1 (P<0.01 expression were upregulated. The direct fetal intervention (C and TP led to early fatty liver changes in all animals without differential changes in insulin secretion. Furthermore, hepatic phosphoenolpyruvate carboxykinase (PEPCK was up-regulated in the fetal controls (P<0.05 and this was opposed by fetal TP (P<0.05. Hepatic estrogen receptor (ERα; P<0.05 and mitogen activated protein kinase kinase 4 (MAP2K4; P<0.05 were increased following fetal TP exposure. Adult liver metabolism and signaling can be altered by early exposure to sex steroids implicating epigenetic regulation of metabolic disturbances that are common in PCOS.

  15. Functional and metabolic changes in the brain in neuropathic pain syndrome against the background of chronic epidural electrostimulation of the spinal cord.

    Sufianov, A A; Shapkin, A G; Sufianova, G Z; Elishev, V G; Barashin, D A; Berdichevskii, V B; Churkin, S V

    2014-08-01

    Changes in functional and metabolic activities of the brain were evaluated by EEG and positron-emission/computer tomography with 18F-fluorodeoxyglucose in patients with neuropathic pain syndrome previous to and 3 months after implantation of a system for chronic epidural spinal cord stimulation. In most cases, the use of a nerve stimulator was followed by alleviation of neuropathic pain and partial normalization of functional and metabolic activities of brain structures responsible for pain perception, emotiogenic, behavioral, and autonomic responses.

  16. Metabolic and functional changes in transgender individuals following cross-sex hormone treatment: Design and methods of the GEnder Dysphoria Treatment in Sweden (GETS study

    Anna Wiik

    2018-06-01

    Full Text Available Background: Although the divergent male and female differentiation depends on key genes, many biological differences seen in men and women are driven by relative differences in estrogen and testosterone levels. Gender dysphoria denotes the distress that gender incongruence with the assigned sex at birth may cause. Gender-affirming treatment includes medical intervention such as inhibition of endogenous sex hormones and subsequent replacement with cross-sex hormones. The aim of this study is to investigate consequences of an altered sex hormone profile on different tissues and metabolic risk factors. By studying subjects undergoing gender-affirming medical intervention with sex hormones, we have the unique opportunity to distinguish between genetic and hormonal effects. Methods: The study is a single center observational cohort study conducted in Stockholm, Sweden. The subjects are examined at four time points; before initiation of treatment, after endogenous sex hormone inhibition, and three and eleven months following sex hormone treatment. Examinations include blood samples, skeletal muscle-, adipose- and skin tissue biopsies, arteriography, echocardiography, carotid Doppler examination, whole body MRI, CT of muscle and measurements of muscle strength. Results: The primary outcome measure is transcriptomic and epigenomic changes in skeletal muscle. Secondary outcome measures include transcriptomic and epigenomic changes associated with metabolism in adipose and skin, muscle strength, fat cell size and ability to release fatty acids from adipose tissue, cardiovascular function, and body composition. Conclusions: This study will provide novel information on the role of sex hormone treatment in skeletal muscle, adipose and skin, and its relation to cardiovascular and metabolic disease. Keywords: Transgender, Sex hormone, Adipose tissue, Skeletal muscle, Epigenetics, Sex change

  17. Influence of Hypothyroidism on Separate Links of Metabolism, Structure and Function of the Heart in Insulin Resistance

    T.Yu. Yuzvenko

    2014-05-01

    Full Text Available The article presents research findings of reduced thyroid function impact on the background of insulin resistance on the specific links of metabolism, structure and function of the heart. It is found that in thyroid dysfunction, the main nosological form of myocardial lesion in female patients without concomitant cardiovascular disease is the development of metabolic endocrine cardiomyopathy. Feature of cardiac lesion is the absence of cardiosclerotic, myocardial and ischemic processes in hypothyroidism. Obscure clinical symptoms of the heart both in apparent and subclinical hypothyroidism are detected. Features of clinical, instrumental and laboratory changes in female patients with impaired thyroid function are a trend to systolic blood pressure increase, the absence of significant dyslipidemia, dysglycemia, and cardiocytolysis and hepatocytolysis. Thyroid hormone deficiency is associated with increased myocardial repolarization heterogeneity: subclinical hypothyroidism is accompanied by violation of repolarization processes and the development of electrical heterogeneity of ventricular myocardium, and in the apparent hypothyroidism changes are more linked with the violation of the homogeneity of the electrical impulse to the atria.

  18. Relationships between Electrokinetic Index of buccal epithelium and some functional and metabolic parameters at men with chronic pyelonephrite

    Iryna G. Kyrylenko

    2016-01-01

      Abstracts   Background. Known for a number of parameters of the body, which through regression equations derived can assess biological age. We examined relationships between electrokinetic mobility buccal epithelium cell nuclei, named Electrokinetic Index (EKI, and some functional and metabolic parameters of body. Methods. Under a observations were 23 men by age 24-70 years with chronic pyelonephrite in the phase of remission. We estimated the EKI, state of the vegetative and hormonal regulation as well as metabolism of cholesterol. Results. We confirned closely correlation (r=-0,89 between Metric Age and EKI. Baevskiy’s Adaptation Potential and Stange’s Test together determines EKI on 28%. RMSSD, VLF and Baevskiy’s Stress Index determines EKI on 31%. Plasma Colesterol and Klimov’s Atherogenicity Coefficient determines EKI on 56%. In summary model of multiple regression with stepwise excluding are currently two last parameters as well as Plasma Testosterone and relative Power Spectral VLF HRV, which together determines EKI on 73%: R=0,868; R2=0,754; Adjusted R2=0,730;F(4,4=31,4; χ2(4=58,9; p<10-5. Conclusion. Electrokinetic Index of buccal epithelium really rellects neuro-endocrine regulation and metabolism of Cholesterol.   Keywords: Electrokinetic Index, Biological Age, HRV, Cholesterol, Testosterone, Cortisol, Relationships.

  19. Ruminant Metabolic Systems Biology: Reconstruction and Integration of Transcriptome Dynamics Underlying Functional Responses of Tissues to Nutrition and Physiological Statea

    Bionaz, Massimo; Loor, Juan J.

    2012-01-01

    High-throughput ‘omics’ data analysis via bioinformatics is one key component of the systems biology approach. The systems approach is particularly well-suited for the study of the interactions between nutrition and physiological state with tissue metabolism and functions during key life stages of organisms such as the transition from pregnancy to lactation in mammals, ie, the peripartal period. In modern dairy cows with an unprecedented genetic potential for milk synthesis, the nature of the physiologic and metabolic adaptations during the peripartal period is multifaceted and involves key tissues such as liver, adipose, and mammary. In order to understand such adaptation, we have reviewed several works performed in our and other labs. In addition, we have used a novel bioinformatics approach, Dynamic Impact Approach (DIA), in combination with partly previously published data to help interpret longitudinal biological adaptations of bovine liver, adipose, and mammary tissue to lactation using transcriptomics datasets. Use of DIA with transcriptomic data from those tissues during normal physiological adaptations and in animals fed different levels of energy prepartum allowed visualization and integration of most-impacted metabolic pathways around the time of parturition. The DIA is a suitable tool for applying the integrative systems biology approach. The ultimate goal is to visualize the complexity of the systems at study and uncover key molecular players involved in the tissue’s adaptations to physiological state or nutrition. PMID:22807626

  20. Systematic Analysis of γ-Aminobutyric Acid (GABA) Metabolism and Function in the Social Amoeba Dictyostelium discoideum*

    Wu, Yuantai; Janetopoulos, Chris

    2013-01-01

    While GABA has been suggested to regulate spore encapsulation in the social amoeba Dictyostelium discoideum, the metabolic profile and other potential functions of GABA during development remain unclear. In this study, we investigated the homeostasis of GABA metabolism by disrupting genes related to GABA metabolism and signaling. Extracellular levels of GABA are tightly regulated during early development, and GABA is generated by the glutamate decarboxylase, GadB, during growth and in early development. However, overexpression of the prespore-specific homologue, GadA, in the presence of GadB reduces production of extracellular GABA. Perturbation of extracellular GABA levels delays the process of aggregation. Cytosolic GABA is degraded by the GABA transaminase, GabT, in the mitochondria. Disruption of a putative vesicular GABA transporter (vGAT) homologue DdvGAT reduces secreted GABA. We identified the GABAB receptor-like family member GrlB as the major GABA receptor during early development, and either disruption or overexpression of GrlB delays aggregation. This delay is likely the result of an abolished pre-starvation response and late expression of several “early” developmental genes. Distinct genes are employed for GABA generation during sporulation. During sporulation, GadA alone is required for generating GABA and DdvGAT is likely responsible for GABA secretion. GrlE but not GrlB is the GABA receptor during late development. PMID:23548898

  1. Sex steroids do not affect muscle weight, oxidative metabolism or cytosolic androgen reception binding of functionally overloaded rat Plantaris muscles

    Max, S. R.; Rance, N.

    1983-01-01

    The effects of sex steroids on muscle weight and oxidative capacity of rat planaris muscles subjected to functional overload by removal of synergistic muscles were investigated. Ten weeks after bilateral synergist removal, plantaris muscles were significantly hypertrophic compared with unoperated controls. After this period, the ability of the muscles to oxide three substrates of oxidative metabolism was assessed. Experimental procedures are discussed and results are presented herein. Results suggest a lack of beneficial effect of sex hormone status on the process of hypertrophy and on biochemical changes in overloaded muscle. Such findings are not consistent with the idea of synergistic effects of sex steroids and muscle usage.

  2. Altered free radical metabolism in acute mountain sickness: implications for dynamic cerebral autoregulation and blood-brain barrier function

    Bailey, D M; Evans, K A; James, P E

    2008-01-01

    We tested the hypothesis that dynamic cerebral autoregulation (CA) and blood-brain barrier (BBB) function would be compromised in acute mountain sickness (AMS) subsequent to a hypoxia-mediated alteration in systemic free radical metabolism. Eighteen male lowlanders were examined in normoxia (21% O...... developed clinical AMS (AMS+) and were more hypoxaemic relative to subjects without AMS (AMS-). A more marked increase in the venous concentration of the ascorbate radical (A(*-)), lipid hydroperoxides (LOOH) and increased susceptibility of low-density lipoprotein (LDL) to oxidation was observed during...

  3. Metabolite Profile Analysis Reveals Functional Effects of 28-Day Vitamin B-6 Restriction on One-Carbon Metabolism and Tryptophan Catabolic Pathways in Healthy Men and Women123

    da Silva, Vanessa R.; Rios-Avila, Luisa; Lamers, Yvonne; Ralat, Maria A.; Midttun, Øivind; Quinlivan, Eoin P.; Garrett, Timothy J.; Coats, Bonnie; Shankar, Meena N.; Percival, Susan S.; Chi, Yueh-Yun; Muller, Keith E.; Ueland, Per Magne; Stacpoole, Peter W.; Gregory, Jesse F.

    2013-01-01

    Suboptimal vitamin B-6 status, as reflected by low plasma pyridoxal 5′-phosphate (PLP) concentration, is associated with increased risk of vascular disease. PLP plays many roles, including in one-carbon metabolism for the acquisition and transfer of carbon units and in the transsulfuration pathway. PLP also serves as a coenzyme in the catabolism of tryptophan. We hypothesize that the pattern of these metabolites can provide information reflecting the functional impact of marginal vitamin B-6 deficiency. We report here the concentration of major constituents of one-carbon metabolic processes and the tryptophan catabolic pathway in plasma from 23 healthy men and women before and after a 28-d controlled dietary vitamin B-6 restriction (restriction yielded increased cystathionine (53% pre- and 76% postprandial; P restriction yielded lower kynurenic acid (22% pre- and 20% postprandial; P restriction and multilevel partial least squares-discriminant analysis supported this conclusion. Thus, plasma concentrations of creatine, cystathionine, kynurenic acid, and 3-hydroxykynurenine jointly reveal effects of vitamin B-6 restriction on the profiles of one-carbon and tryptophan metabolites and serve as biomarkers of functional effects of marginal vitamin B-6 deficiency. PMID:23966327

  4. Metabolite profile analysis reveals functional effects of 28-day vitamin B-6 restriction on one-carbon metabolism and tryptophan catabolic pathways in healthy men and women.

    da Silva, Vanessa R; Rios-Avila, Luisa; Lamers, Yvonne; Ralat, Maria A; Midttun, Øivind; Quinlivan, Eoin P; Garrett, Timothy J; Coats, Bonnie; Shankar, Meena N; Percival, Susan S; Chi, Yueh-Yun; Muller, Keith E; Ueland, Per Magne; Stacpoole, Peter W; Gregory, Jesse F

    2013-11-01

    Suboptimal vitamin B-6 status, as reflected by low plasma pyridoxal 5'-phosphate (PLP) concentration, is associated with increased risk of vascular disease. PLP plays many roles, including in one-carbon metabolism for the acquisition and transfer of carbon units and in the transsulfuration pathway. PLP also serves as a coenzyme in the catabolism of tryptophan. We hypothesize that the pattern of these metabolites can provide information reflecting the functional impact of marginal vitamin B-6 deficiency. We report here the concentration of major constituents of one-carbon metabolic processes and the tryptophan catabolic pathway in plasma from 23 healthy men and women before and after a 28-d controlled dietary vitamin B-6 restriction (restriction yielded increased cystathionine (53% pre- and 76% postprandial; P restriction yielded lower kynurenic acid (22% pre- and 20% postprandial; P restriction and multilevel partial least squares-discriminant analysis supported this conclusion. Thus, plasma concentrations of creatine, cystathionine, kynurenic acid, and 3-hydroxykynurenine jointly reveal effects of vitamin B-6 restriction on the profiles of one-carbon and tryptophan metabolites and serve as biomarkers of functional effects of marginal vitamin B-6 deficiency.

  5. Intermittent fasting protects against the deterioration of cognitive function, energy metabolism and dyslipidemia in Alzheimer's disease-induced estrogen deficient rats.

    Shin, Bae Kun; Kang, Suna; Kim, Da Sol; Park, Sunmin

    2018-02-01

    Intermittent fasting may be an effective intervention to protect against age-related metabolic disturbances, although it is still controversial. Here, we investigated the effect of intermittent fasting on the deterioration of the metabolism and cognitive functions in rats with estrogen deficiency and its mechanism was also explored. Ovariectomized rats were infused with β-amyloid (25-35; Alzheimer's disease) or β-amyloid (35-25, Non-Alzheimer's disease; normal cognitive function) into the hippocampus. Each group was randomly divided into two sub-groups: one with intermittent fasting and the other fed ad libitum: Alzheimer's disease-ad libitum, Alzheimer's disease-intermittent fasting, Non-Alzheimer's disease-ad libitum, and Non-Alzheimer's disease-intermittent fasting. Rats in the intermittent fasting groups had a restriction of food consumption to a 3-h period every day. Each group included 10 rats and all rats fed a high-fat diet for four weeks. Interestingly, Alzheimer's disease increased tail skin temperature more than Non-Alzheimer's disease and intermittent fasting prevented the increase. Alzheimer's disease reduced bone mineral density in the spine and femur compared to the Non-Alzheimer's disease, whereas bone mineral density in the hip and leg was reduced by intermittent fasting. Fat mass only in the abdomen was decreased by intermittent fasting. Intermittent fasting decreased food intake without changing energy expenditure. Alzheimer's disease increased glucose oxidation, whereas intermittent fasting elevated fat oxidation as a fuel source. Alzheimer's disease and intermittent fasting deteriorated insulin resistance in the fasting state but intermittent fasting decreased serum glucose levels after oral glucose challenge by increasing insulin secretion. Alzheimer's disease deteriorated short and spatial memory function compared to the Non-Alzheimer's disease, whereas intermittent fasting prevented memory loss in comparison to ad libitum. Unexpectedly

  6. Is bisphenol S a safe substitute for bisphenol A in terms of metabolic function? An in vitro study

    Héliès-Toussaint, Cécile; Peyre, Ludovic; Costanzo, Claudia; Chagnon, Marie-Christine; Rahmani, Roger

    2014-01-01

    As bisphenol A (BPA) has been shown to induce adverse effects on human health, especially through the activation of endocrine pathways, it is about to be withdrawn from the European market and replaced by analogues such as bisphenol S (BPS). However, toxicological data on BPS is scarce, and so it is necessary to evaluate the possible effects of this compound on human health. We compared the effect of BPA and BPS on obesity and hepatic steatosis processes using low doses in the same range as those found in the environment. Two in vitro models were used, the adipose cell line 3T3-L1 and HepG2 cells, representative of hepatic functions. We analyzed different parameters such as lipid and glucose uptakes, lipolysis, leptin production and the modulation of genes involved in lipid metabolism and energy balance. BPA and BPS induced an increase in the lipid content in the 3T3-L1 cell line and more moderately in the hepatic cells. We also observed a decrease in lipolysis after bisphenol treatment of adipocytes, but only BPS was involved in the increase in glucose uptake and leptin production. These latter effects could be linked to the modulation of SREBP-1c, PPARγ, aP2 and ERRα and γ genes after exposure to BPA, whereas BPS seems to target the PGC1α and the ERRγ genes. The findings suggest that both BPA and BPS could be involved in obesity and steatosis processes, but through two different metabolic pathways. - Highlights: • The non-monotonic effects of BPA and BPS act through 2 different metabolic pathways. • BPA and BPS induce an increase in the lipid content in adipocytes and hepatic cells. • BPS increased leptin production and glucose uptake in adipocyte and hepatocyte. • BPA and BPS could participate in metabolic deregulations leading to obesity or NAFLD

  7. Effects of ammonia-N stress on metabolic and immune function via the neuroendocrine system in Litopenaeus vannamei.

    Cui, Yanting; Ren, Xianyun; Li, Jian; Zhai, Qianqian; Feng, Yanyan; Xu, Yang; Ma, Li

    2017-05-01

    The purpose of this study was to evaluate the immunological responses, such as phenoloxidase (PO), antibacterial, and bacteriolytic activities, and metabolic variables, such as oxyhemocyanin, lactate, and glucose levels, of Litopenaeus vannamei exposed to ambient ammonia-N at 0, 2.5, 5, 7.5, and 10 mg/L for 0, 3, 6, 12, 24, and 48 h, and determine the effects of the eyestalk hormone on the metabolic and immune functions of unilateral eyestalk-ablated L. vannamei exposed to ambient ammonia-N at 10 mg/L. The actual concentrations of the control and test solutions were 0.04, 2.77, 6.01, 8.30, and 11.36 mg/L for ammonia-N and 0.01, 0.15, 0.32, 0.44, and 0.60 mg/L for NH 3 -N (unionized ammonia). The results showed a significant decrease in the PO, antibacterial, and bacteriolytic activities in the plasma as well as a significant increase in the glucose and lactate levels and decreased oxyhemocyanin levels in the hemolymph of L. vannamei exposed to elevated ammonia-N levels. These findings indicated that L. vannamei exposed to ammonia-N might demonstrate weakened metabolic and immunological responses. Moreover, eyestalk removal caused a dramatic decrease in PO, antibacterial, and bacteriolytic activities, which indicated that the eyestalk hormone in L. vannamei exhibited a higher immune response due to the induction of protective mechanisms against ammonia-N stress. Eyestalk removal also caused a dramatic decrease in glucose and lactate levels, suggesting that the eyestalk hormone is involved in glucose metabolism to meet the energy requirements under ammonia-N stress conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Is bisphenol S a safe substitute for bisphenol A in terms of metabolic function? An in vitro study

    Héliès-Toussaint, Cécile, E-mail: cecile.helies@toulouse.inra.fr [INRA, TOXALIM, 180 chemin de Tournefeuille, 31027 Toulouse (France); Université de Toulouse III, INP, ENVT, UPS, 31027 Toulouse (France); Peyre, Ludovic [INRA, UMR 1331 TOXALIM, 400 route des Chappes, BP 167, 06903 Sophia-Antipolis (France); Costanzo, Claudia [INRA, TOXALIM, 180 chemin de Tournefeuille, 31027 Toulouse (France); Université de Toulouse III, INP, ENVT, UPS, 31027 Toulouse (France); Chagnon, Marie-Christine [Nutox Laboratory, Derttech “Packtox”, INSERM UMR 866, AgroSup Dijon, 1 esplanade Erasme, 21000 Dijon (France); Rahmani, Roger [INRA, UMR 1331 TOXALIM, 400 route des Chappes, BP 167, 06903 Sophia-Antipolis (France)

    2014-10-15

    As bisphenol A (BPA) has been shown to induce adverse effects on human health, especially through the activation of endocrine pathways, it is about to be withdrawn from the European market and replaced by analogues such as bisphenol S (BPS). However, toxicological data on BPS is scarce, and so it is necessary to evaluate the possible effects of this compound on human health. We compared the effect of BPA and BPS on obesity and hepatic steatosis processes using low doses in the same range as those found in the environment. Two in vitro models were used, the adipose cell line 3T3-L1 and HepG2 cells, representative of hepatic functions. We analyzed different parameters such as lipid and glucose uptakes, lipolysis, leptin production and the modulation of genes involved in lipid metabolism and energy balance. BPA and BPS induced an increase in the lipid content in the 3T3-L1 cell line and more moderately in the hepatic cells. We also observed a decrease in lipolysis after bisphenol treatment of adipocytes, but only BPS was involved in the increase in glucose uptake and leptin production. These latter effects could be linked to the modulation of SREBP-1c, PPARγ, aP2 and ERRα and γ genes after exposure to BPA, whereas BPS seems to target the PGC1α and the ERRγ genes. The findings suggest that both BPA and BPS could be involved in obesity and steatosis processes, but through two different metabolic pathways. - Highlights: • The non-monotonic effects of BPA and BPS act through 2 different metabolic pathways. • BPA and BPS induce an increase in the lipid content in adipocytes and hepatic cells. • BPS increased leptin production and glucose uptake in adipocyte and hepatocyte. • BPA and BPS could participate in metabolic deregulations leading to obesity or NAFLD.

  9. The clinical obesity maintenance model: an integration of psychological constructs including mood, emotional regulation, disordered overeating, habitual cluster behaviours, health literacy and cognitive function.

    Raman, Jayanthi; Smith, Evelyn; Hay, Phillipa

    2013-01-01

    Psychological distress and deficits in executive functioning are likely to be important barriers to effective weight loss maintenance. The purpose of this paper is twofold. First, in the light of recent evidence in the fields of neuropsychology and obesity, particularly on the deficits in the executive function in overweight and obese individuals, a conceptual and theoretical framework of obesity maintenance is introduced by way of a clinical obesity maintenance model (COMM). It is argued that psychological variables, that of habitual cluster Behaviors, emotional dysregulation, mood, and health literacy, interact with executive functioning and impact on the overeating/binge eating behaviors of obese individuals. Second, cognizant of this model, it is argued that the focus of obesity management should be extended to include a broader range of maintaining mechanisms, including but not limited to cognitive deficits. Finally, a discussion on potential future directions in research and practice using the COMM is provided.

  10. The Clinical Obesity Maintenance Model: An Integration of Psychological Constructs including Mood, Emotional Regulation, Disordered Overeating, Habitual Cluster Behaviours, Health Literacy and Cognitive Function

    Jayanthi Raman

    2013-01-01

    Full Text Available Psychological distress and deficits in executive functioning are likely to be important barriers to effective weight loss maintenance. The purpose of this paper is twofold. First, in the light of recent evidence in the fields of neuropsychology and obesity, particularly on the deficits in the executive function in overweight and obese individuals, a conceptual and theoretical framework of obesity maintenance is introduced by way of a clinical obesity maintenance model (COMM. It is argued that psychological variables, that of habitual cluster Behaviors, emotional dysregulation, mood, and health literacy, interact with executive functioning and impact on the overeating/binge eating behaviors of obese individuals. Second, cognizant of this model, it is argued that the focus of obesity management should be extended to include a broader range of maintaining mechanisms, including but not limited to cognitive deficits. Finally, a discussion on potential future directions in research and practice using the COMM is provided.

  11. The radical scavenger edaravone improves neurologic function and perihematomal glucose metabolism after acute intracerebral hemorrhage.

    Shang, Hanbing; Cui, Derong; Yang, Dehua; Liang, Sheng; Zhang, Weifeng; Zhao, Weiguo

    2015-01-01

    Oxidative injury caused by reactive oxygen species plays an important role in the progression of intracerebral hemorrhage (ICH)-induced secondary brain injury. Previous studies have demonstrated that the free radical scavenger edaravone may prevent neuronal injury and brain edema after ICH. However, the influence of edaravone on cerebral metabolism in the early stages after ICH and the underlying mechanism have not been fully investigated. In the present study, we investigated the effect of edaravone on perihematomal glucose metabolism using (18)F-fluorordeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). Additionally, the neurologic deficits, brain edemas, and cell death that followed ICH were quantitatively analyzed. After blood infusion, the rats treated with edaravone showed significant improvement in both forelimb placing and corner turn tests compared with those treated with vehicle. Moreover, the brain water content of the edaravone-treated group was significantly decreased compared with that of the vehicle group on day 3 after ICH. PET/CT images of ICH rats exhibited obvious decreases in FDG standardized uptake values in perihematomal region on day 3, and the lesion-to-normal ratio of the edaravone-treated ICH rats was significantly increased compared with that of the control rats. Calculation of the brain injury volumes from the PET/CT images revealed that the volumes of the blood-induced injuries were significantly smaller in the edaravone group compared with the vehicle group. Terminal Deoxynucleotidyl Transferase-mediated dUTP Nick End Labeling assays performed 3 days after ICH revealed that the numbers of apoptotic cells in perihematomal region of edaravone-treated ICH rats were decreased relative to the vehicle group. Thus, the present study demonstrates that edaravone has scavenging properties that attenuate neurologic behavioral deficits and brain edema in the early period of ICH. Additionally, edaravone may improve

  12. Development of a comprehensive survey of sexuality issues including a self-report version of the International Spinal Cord Injury sexual function basic data sets.

    New, P W; Currie, K E

    2016-08-01

    Questionnaire development, validation and completion. Develop comprehensive survey of sexuality issues including validated self-report versions of the International Spinal Cord Injury male sexual function and female sexual and reproductive function basic data sets (SR-iSCI-sexual function). People with spinal cord damage (SCD) living in the community, Australia from August 2013 to June 2014. An iterative process involving rehabilitation medicine clinicians, a nurse specialising in sexuality issues in SCD and people with SCD who developed a comprehensive survey that included the SR-iSCI-sexual function. Participants recruitment through spinal rehabilitation review clinic and community organisations that support people with SCD. Surveys completed by 154 people. Most were male (n=101, 65.6%). Respondents' median age was 50 years (interquartile range (IQR) 38-58), and they were a median of 10 years (IQR 4-20) after the onset of SCD. Sexual problems unrelated to SCD were reported by 12 (8%) respondents, and 114 (n=75.5%) reported sexual problems because of SCD. Orgasms were much less likely (χ(2)=13.1, P=0.006) to be normal in males (n=5, 5%) compared with females (n=11, 22%). Males had significantly worse (χ(2)=26.0, P=0.001) psychogenic genital functioning (normal n=9, 9%) than females (normal n=13, 26%) and worse (χ(2)=10.8, P=0.013) reflex genital functioning. Normal ejaculation was reported in only three (3%) men. Most (n=26, 52%) women reported reduced or absent menstruation pattern since SCD. The SR-iSCI-sexual function provides a useful tool for researchers and clinicians to collect information regarding patient-reported sexual functioning after SCD and to facilitate comparative studies.

  13. Functional and clinical relevance of novel and known PCSK1 variants for childhood obesity and glucose metabolism

    Dennis Löffler

    2017-03-01

    Full Text Available Objective: Variants in Proprotein Convertase Subtilisin/Kexin Type 1 (PCSK1 may be causative for obesity as suggested by monogenic cases and association studies. Here we assessed the functional relevance in experimental studies and the clinical relevance through detailed metabolic phenotyping of newly identified and known PCSK1 variants in children. Results: In 52 obese children selected for elevated proinsulin levels and/or impaired glucose tolerance, we found eight known variants and two novel heterozygous variants (c.1095 + 1G > A and p.S24C by sequencing the PCSK1 gene. Patients with the new variants presented with extreme obesity, impaired glucose tolerance, and PCOS. Functionally, c.1095 + 1G > A caused skipping of exon8 translation and a complete loss of enzymatic activity. The protein was retained within the endoplasmic reticulum (ER causing ER stress. The p.S24C variant had no functional effect on protein size, cell trafficking, or enzymatic activity. The known variants rs6230, rs35753085, and rs725522 in the 5′ end did not affect PCSK1 promoter activity.In clinical association studies in 1673 lean and obese children, we confirmed associations of rs6232 and rs6234 with BMI-SDS and of rs725522 with glucose stimulated insulin secretion and Matsuda index. We did not find the new variants in any other subjects. Conclusions: We identified and functionally characterized two rare novel PCSK1 variants of which c.1095 + 1G > A caused complete loss of protein function. In addition to confirming rs6232 and rs6234 in PCSK1 as polygenic risk variants for childhood obesity, we describe an association of rs725522 with insulin metabolism. Our results support the contribution of PCSK1 variants to obesity predisposition in children. Keywords: PCSK1, PC1/3, Obesity, Children, Prohormone convertase 1/3

  14. Characterization of Genotoxic Response to 15 Multiwalled Carbon Nanotubes with Variable Physicochemical Properties Including Surface Functionalizations in the FE1-Muta(TM) Mouse Lung Epithelial Cell Line

    Jackson, Petra; Kling, Kirsten; Jensen, Keld Alstrup

    2015-01-01

    Carbon nanotubes vary greatly in physicochemical properties. We compared cytotoxic and genotoxic response to 15 multiwalled carbon nanotubes (MWCNT) with varying physicochemical properties to identify drivers of toxic responses. The studied MWCNT included OECD Working Party on Manufactured...... Nanomaterials (WPMN) (NM-401, NM-402, and NM-403), materials (NRCWE-026 and MWCNT-XNRI-7), and three sets of surface-modified MWCNT grouped by physical characteristics (thin, thick, and short I-III, respectively). Each Groups I-III included pristine, hydroxylated and carboxylated MWCNT. Group III also included...... an amino-functionalized MWCNT. The level of surface functionalization of the MWCNT was low. The level and type of elemental impurities of the MWCNT varied by...

  15. Noninvasive quantification of cerebral metabolic rate for glucose in rats using 18F-FDG PET and standard input function

    Hori, Yuki; Ihara, Naoki; Teramoto, Noboru; Kunimi, Masako; Honda, Manabu; Kato, Koichi; Hanakawa, Takashi

    2015-01-01

    Measurement of arterial input function (AIF) for quantitative positron emission tomography (PET) studies is technically challenging. The present study aimed to develop a method based on a standard arterial input function (SIF) to estimate input function without blood sampling. We performed 18F-fluolodeoxyglucose studies accompanied by continuous blood sampling for measurement of AIF in 11 rats. Standard arterial input function was calculated by averaging AIFs from eight anesthetized rats, after normalization with body mass (BM) and injected dose (ID). Then, the individual input function was estimated using two types of SIF: (1) SIF calibrated by the individual's BM and ID (estimated individual input function, EIFNS) and (2) SIF calibrated by a single blood sampling as proposed previously (EIF1S). No significant differences in area under the curve (AUC) or cerebral metabolic rate for glucose (CMRGlc) were found across the AIF-, EIFNS-, and EIF1S-based methods using repeated measures analysis of variance. In the correlation analysis, AUC or CMRGlc derived from EIFNS was highly correlated with those derived from AIF and EIF1S. Preliminary comparison between AIF and EIFNS in three awake rats supported an idea that the method might be applicable to behaving animals. The present study suggests that EIFNS method might serve as a noninvasive substitute for individual AIF measurement. PMID:25966947

  16. Functional Effects of Prebiotic Fructans in Colon Cancer and Calcium Metabolism in Animal Models.

    Rivera-Huerta, Marisol; Lizárraga-Grimes, Vania Lorena; Castro-Torres, Ibrahim Guillermo; Tinoco-Méndez, Mabel; Macías-Rosales, Lucía; Sánchez-Bartéz, Francisco; Tapia-Pérez, Graciela Guadalupe; Romero-Romero, Laura; Gracia-Mora, María Isabel

    2017-01-01

    Inulin-type fructans are polymers of fructose molecules and are known for their capacity to enhance absorption of calcium and magnesium, to modulate gut microbiota and energy metabolism, and to improve glycemia. We evaluated and compared the effects of Chicory inulin "Synergy 1®" and inulin from Mexican agave "Metlin®" in two experimental models of colon cancer and bone calcium metabolism in mice and rats. Inulins inhibited the development of dextran sulfate sodium-induced colitis and colon cancer in mice; these fructans reduced the concentration of tumor necrosis factor alpha and prevented the formation of intestinal polyps, villous atrophy, and lymphoid hyperplasia. On the other hand, inulin treatments significantly increased bone densitometry (femur and vertebra) in ovariectomized rats without altering the concentration of many serum biochemical parameters and urinary parameters. Histopathology results were compared between different experimental groups. There were no apparent histological changes in rats treated with inulins and a mixture of inulins-isoflavones. Our results showed that inulin-type fructans have health-promoting properties related to enhanced calcium absorption, potential anticancer properties, and anti-inflammatory effects. The use of inulin as a prebiotic can improve health and prevent development of chronic diseases such as cancer and osteoporosis.

  17. Functional Effects of Prebiotic Fructans in Colon Cancer and Calcium Metabolism in Animal Models

    Marisol Rivera-Huerta

    2017-01-01

    Full Text Available Inulin-type fructans are polymers of fructose molecules and are known for their capacity to enhance absorption of calcium and magnesium, to modulate gut microbiota and energy metabolism, and to improve glycemia. We evaluated and compared the effects of Chicory inulin “Synergy 1®” and inulin from Mexican agave “Metlin®” in two experimental models of colon cancer and bone calcium metabolism in mice and rats. Inulins inhibited the development of dextran sulfate sodium-induced colitis and colon cancer in mice; these fructans reduced the concentration of tumor necrosis factor alpha and prevented the formation of intestinal polyps, villous atrophy, and lymphoid hyperplasia. On the other hand, inulin treatments significantly increased bone densitometry (femur and vertebra in ovariectomized rats without altering the concentration of many serum biochemical parameters and urinary parameters. Histopathology results were compared between different experimental groups. There were no apparent histological changes in rats treated with inulins and a mixture of inulins-isoflavones. Our results showed that inulin-type fructans have health-promoting properties related to enhanced calcium absorption, potential anticancer properties, and anti-inflammatory effects. The use of inulin as a prebiotic can improve health and prevent development of chronic diseases such as cancer and osteoporosis.

  18. Photosynthetic metabolism and quality of Eugenia pyriformis Cambess. seedlings on substrate function and water levels.

    Scalon, Silvana P Q; Jeromini, Tatiane S; Mussury, Rosilda M; Dresch, Daiane M

    2014-12-01

    The aim of this research was to evaluate the quality and photosynthetic metabolism of "uvaia" seedlings (Eugenia pyriformis Cambess.) on different substrates and water regimes. The seeds were sown in tubes of 50 x 190 mm in the following substrates: Sand (S), Latosol + Sand (L + S) (1:1), Latosol + Sand + Semi Decomposed Poultry Litter (L + S1 + PL) ( 1:1:0.5), Latosol + Sand + Semi Decomposed Poultry Litter (L + S2 + PL) (1:2:0.5), Latosol + Bioplant® (L + B) (1:1), and the water levels assessed were 50, 75 and 100% of water retention capacity. At 60, 90, 120 and 150 days the seedlings were evaluated according to their chlorophyll index, leaf area (cm2) and Dickson Quality Index (DQI) and at 150 days their internal concentration of carbon (mol m-2 s-1), stomatal conductance (mol m-2 s-1), transpiration rate (mmol m-2 s-1), photosynthesis (µmol m-2 s-1) and efficiency of water use (µmol de CO2 / mmol de H2O). Until their 150th days, the seedlings had higher quality and photosynthetic metabolism when cultured with substrates containing latosol + sand + poultry litter on the two variations assessed and water retention capacity of 50%.

  19. Photosynthetic metabolism and quality of Eugenia pyriformis Cambess. seedlings on substrate function and water levels

    SILVANA P.Q. SCALON

    2014-12-01

    Full Text Available The aim of this research was to evaluate the quality and photosynthetic metabolism of “uvaia” seedlings (Eugenia pyriformis Cambess. on different substrates and water regimes. The seeds were sown in tubes of 50 x 190 mm in the following substrates: Sand (S, Latosol + Sand (L + S (1:1, Latosol + Sand + Semi Decomposed Poultry Litter (L + S1 + PL ( 1:1:0.5, Latosol + Sand + Semi Decomposed Poultry Litter (L + S2 + PL (1:2:0.5, Latosol + Bioplant® (L + B (1:1, and the water levels assessed were 50, 75 and 100% of water retention capacity. At 60, 90, 120 and 150 days the seedlings were evaluated according to their chlorophyll index, leaf area (cm2 and Dickson Quality Index (DQI and at 150 days their internal concentration of carbon (mol m–2 s–1, stomatal conductance (mol m–2 s–1, transpiration rate (mmol m–2 s–1, photosynthesis (µmol m–2 s–1 and efficiency of water use (µmol de CO2 / mmol de H2O. Until their 150th days, the seedlings had higher quality and photosynthetic metabolism when cultured with substrates containing latosol + sand + poultry litter on the two variations assessed and water retention capacity of 50%.

  20. Duodenal Cytochrome b (DCYTB in Iron Metabolism: An Update on Function and Regulation

    Darius J. R. Lane

    2015-03-01

    Full Text Available Iron and ascorbate are vital cellular constituents in mammalian systems. The bulk-requirement for iron is during erythropoiesis leading to the generation of hemoglobin-containing erythrocytes. Additionally; both iron and ascorbate are required as co-factors in numerous metabolic reactions. Iron homeostasis is controlled at the level of uptake; rather than excretion. Accumulating evidence strongly suggests that in addition to the known ability of dietary ascorbate to enhance non-heme iron absorption in the gut; ascorbate regulates iron homeostasis. The involvement of ascorbate in dietary iron absorption extends beyond the direct chemical reduction of non-heme iron by dietary ascorbate. Among other activities; intra-enterocyte ascorbate appears to be involved in the provision of electrons to a family of trans-membrane redox enzymes; namely those of the cytochrome b561 class. These hemoproteins oxidize a pool of ascorbate on one side of the membrane in order to reduce an electron acceptor (e.g., non-heme iron on the opposite side of the membrane. One member of this family; duodenal cytochrome b (DCYTB; may play an important role in ascorbate-dependent reduction of non-heme iron in the gut prior to uptake by ferrous-iron transporters. This review discusses the emerging relationship between cellular iron homeostasis; the emergent “IRP1-HIF2α axis”; DCYTB and ascorbate in relation to iron metabolism.

  1. Influence of functional nutrients on insulin resistance in horses with equine metabolic syndrome

    Krzysztof Marycz, Eberhard Moll and Jakub Grzesiak

    2014-04-01

    Full Text Available The obesity is a rising health problem both in veterinary and human medicine. In equine medicine excessive body weight is frequently related to insulin resistance and laminitis as is defined as equine metabolic syndrome (EMS. The dietetic management is considered as the crucial part of treatment strategy in the course of EMS. The main feeding recommendation is to administer the low energy diet in order to restore insulin efficiency and to lower body weight. In this study 14 horses of different breed, both sexes and different ages with diagnosed equine metabolic syndrome were fed, concurrently, with oats (3g/kg bw, hay (15g/kg bw and experimental dietary supplement containing selected herbs, aminoacids, butyric acid derivative, biotin and selected dietetic plant like artichoke. The influence of above dietary protocol on body weight, insulin level, and adipose tissue morphometry was investigated in horses from group A. Horses from group B fed only with oats (3g/kg bw and hay (15g/kg bw served as a control. Results of the experiment indicated that tested supplement could improve insulin efficiency and reduce body mass in experimental horses group.

  2. Biotin deprivation impairs mitochondrial structure and function and has implications for inherited metabolic disorders.

    Ochoa-Ruiz, Estefanía; Díaz-Ruiz, Rodrigo; Hernández-Vázquez, Alaín de J; Ibarra-González, Isabel; Ortiz-Plata, Alma; Rembao, Daniel; Ortega-Cuéllar, Daniel; Viollet, Benoit; Uribe-Carvajal, Salvador; Corella, José Ahmed; Velázquez-Arellano, Antonio

    2015-11-01

    Certain inborn errors of metabolism result from deficiencies in biotin containing enzymes. These disorders are mimicked by dietary absence or insufficiency of biotin, ATP deficit being a major effect,whose responsible mechanisms have not been thoroughly studied. Here we show that in rats and cultured cells it is the result of reduced TCA cycle flow, partly due to deficient anaplerotic biotin-dependent pyruvate carboxylase. This is accompanied by diminished flow through the electron transport chain, augmented by deficient cytochrome c oxidase (complex IV) activity with decreased cytochromes and reduced oxidative phosphorylation. There was also severe mitochondrial damage accompanied by decrease of mitochondria, associated with toxic levels of propionyl CoA as shown by carnitine supplementation studies, which explains the apparently paradoxical mitochondrial diminution in the face of the energy sensor AMPK activation, known to induce mitochondria biogenesis. This idea was supported by experiments on AMPK knockout mouse embryonic fibroblasts (MEFs). The multifactorial ATP deficit also provides a plausible basis for the cardiomyopathy in patients with propionic acidemia, and other diseases.Additionally, systemic inflammation concomitant to the toxic state might explain our findings of enhanced IL-6, STAT3 and HIF-1α, associated with an increase of mitophagic BNIP3 and PINK proteins, which may further increase mitophagy. Together our results imply core mechanisms of energy deficit in several inherited metabolic disorders.

  3. The Effects of Different Isocaloric Oral Nutrient Solutions on Psychophysical, Metabolic, Cognitive, and Olfactory Function in Young Male Subjects.

    Bachlechner, Stephan; Denzer-Lippmann, Melanie Y; Wielopolski, Jan; Fischer, Marie; Buettner, Andrea; Doerfler, Arndt; Schöfl, Christof; Münch, Gerald; Kornhuber, Johannes; Thürauf, Norbert

    2017-01-01

    Food intake influences human cognition, olfaction, hunger, and food craving. However, little research has been done in this field to elucidate the effects of different nutrients. Thus, the goal of our study was to investigate the effects of oral ingestion of different nutrient solutions on olfactory, cognitive, metabolic and psychophysical function. Twenty healthy men participated in our study employing a double-blind, cross-over, repeated measurement design. Participants were tested on four different study days. Each day participants received, in randomized order, one of three isocaloric (protein, carbohydrate or fat 600 kcal, 1,500 mL) solutions or a placebo. Olfactory and cognitive tests (monitoring only) were conducted three times, i.e., 60 min before the beginning of nutrient intake, following oral ingestion of the solution and 60, and 240 min after. Psychophysical and metabolic function tests (active grehlin, desacyl ghrelin, insulin, glucagon, glucose, triglyceride, urea) were performed 7 times on each examination day (observation period: -60 min, 0 = solution intake, +60, +120, +180, +240, and +300 min). Ratings of hunger and food craving significantly differed over the observation period with lowest ratings following application of the protein solution. Highest ratings of craving were found following placebo intake. We further observed a significant positive correlation of active grehlin with hunger and fat, protein and sweets craving for each nutrient solution. Active grehlin significantly correlated with carbohydrate craving for carbohydrate and fat solution and with vegetable craving for fat solution only. Hunger hormone levels, hunger and food craving ratings demonstrated that the hierarchical order that appears in satiating efficiencies of isovolumetric-isocaloric ingested macronutrients is protein > fat > carbohydrate. Our study reveals that the type of nutrient exerts a significant influence on metabolic parameters, hunger and food craving.

  4. Economic insecurity during the Great Recession and metabolic, inflammatory and liver function biomarkers: analysis of the UK Household Longitudinal Study.

    Niedzwiedz, Claire L; Katikireddi, Srinivasa Vittal; Reeves, Aaron; McKee, Martin; Stuckler, David

    2017-10-01

    Economic insecurity correlates with adverse health outcomes, but the biological pathways involved are not well understood. We examine how changes in economic insecurity relate to metabolic, inflammatory and liver function biomarkers. Blood analyte data were taken from 6520 individuals (aged 25-59 years) participating in Understanding Society. Economic insecurity was measured using an indicator of subjective financial strain and by asking participants whether they had missed any bill, council tax, rent or mortgage payments in the past year. We investigated longitudinal changes in economic insecurity (remained secure, increase in economic insecurity, decrease in economic insecurity, remained insecure) and the accumulation of economic insecurity. Linear regression models were calculated for nine (logged) biomarker outcomes related to metabolic, inflammatory, liver and kidney function (as falsification tests), adjusting for potential confounders. Compared with those who remained economically stable, people who experienced consistent economic insecurity (using both measures) had worsened levels of high-density lipoprotein (HDL)-cholesterol, triglycerides, C reactive protein (CRP), fibrinogen and glycated haemoglobin. Increased economic insecurity was associated with adverse levels of HDL-cholesterol (0.955, 95% CI 0.929 to 0.982), triglycerides (1.077, 95% CI 1.018 to 1.139) and CRP (1.114, 95% CI 1.012 to 1.227), using the measure of financial strain. Results for the other measure were generally consistent, apart from the higher levels of gamma-glutamyl transferase observed among those experiencing persistent insecurity (1.200, 95% CI 1.110 to 1.297). Economic insecurity is associated with adverse metabolic and inflammatory biomarkers (particularly HDL-cholesterol, triglycerides and CRP), heightening risk for a range of health conditions. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No

  5. The Effects of Different Isocaloric Oral Nutrient Solutions on Psychophysical, Metabolic, Cognitive, and Olfactory Function in Young Male Subjects

    Stephan Bachlechner

    2017-11-01

    Full Text Available Food intake influences human cognition, olfaction, hunger, and food craving. However, little research has been done in this field to elucidate the effects of different nutrients. Thus, the goal of our study was to investigate the effects of oral ingestion of different nutrient solutions on olfactory, cognitive, metabolic and psychophysical function. Twenty healthy men participated in our study employing a double-blind, cross-over, repeated measurement design. Participants were tested on four different study days. Each day participants received, in randomized order, one of three isocaloric (protein, carbohydrate or fat 600 kcal, 1,500 mL solutions or a placebo. Olfactory and cognitive tests (monitoring only were conducted three times, i.e., 60 min before the beginning of nutrient intake, following oral ingestion of the solution and 60, and 240 min after. Psychophysical and metabolic function tests (active grehlin, desacyl ghrelin, insulin, glucagon, glucose, triglyceride, urea were performed 7 times on each examination day (observation period: −60 min, 0 = solution intake, +60, +120, +180, +240, and +300 min. Ratings of hunger and food craving significantly differed over the observation period with lowest ratings following application of the protein solution. Highest ratings of craving were found following placebo intake. We further observed a significant positive correlation of active grehlin with hunger and fat, protein and sweets craving for each nutrient solution. Active grehlin significantly correlated with carbohydrate craving for carbohydrate and fat solution and with vegetable craving for fat solution only. Hunger hormone levels, hunger and food craving ratings demonstrated that the hierarchical order that appears in satiating efficiencies of isovolumetric-isocaloric ingested macronutrients is protein > fat > carbohydrate. Our study reveals that the type of nutrient exerts a significant influence on metabolic parameters, hunger and food

  6. Preliminary evaluation of MRI-derived input function for quantitative measurement of glucose metabolism in an integrated PET-MRI

    Anazodo, Udunna; Kewin, Matthew; Finger, Elizabeth; Thiessen, Jonathan; Hadway, Jennifer; Butler, John; Pavlosky, William; Prato, Frank; Thompson, Terry; St Lawrence, Keith

    2015-01-01

    PET semi-quantitative methods such as relative uptake value can be robust but offer no biological information and do not account for intra-subject variability in tracer administration or clearance. Simultaneous multimodal measurements that combine PET and MRI not only permit crucial multiparametric measurements, it provides means of applying tracer kinetic modelling without the need for serial arterial blood sampling. In this study we adapted an image-derived input function (IDIF) method to improve characterization of glucose metabolism in an ongoing dementia study. Here we present preliminary results in a small group of frontotemporal dementia patients and controls. IDIF was obtained directly from dynamic PET data guided by regions of interest drawn on carotid vessels on high resolution T1-weighted MR Images. IDIF was corrected for contamination of non-arterial voxels. A validation of the method was performed in a porcine model in a PET-CT scanner comparing IDIF to direct arterial blood samples. Metabolic rate of glucose (CMRglc) was measured voxel-by-voxel in gray matter producing maps that were compared between groups. Net influx rate (Ki) and global mean CMRglc are reported. A good correlation (r = 0.9 p<0.0001) was found between corrected IDIF and input function measured from direct arterial blood sampling in the validation study. In 3 FTD and 3 controls, a trend towards hypometabolism was found in frontal, temporal and parietal lobes similar to significant differences previously reported by other groups. The global mean CMRglc and Ki observed in control subjects are in line with previous reports. In general, kinetic modelling of PET-FDG using an MR-IDIF can improve characterization of glucose metabolism in dementia. This method is feasible in multimodal studies that aim to combine PET molecular imaging with MRI as dynamic PET can be acquired along with multiple MRI measurements.

  7. Effects of Tight Versus Non Tight Control of Metabolic Acidosis on Early Renal Function After Kidney Transplantation

    Farhad Etezadi

    2012-09-01

    Full Text Available Background Recently, several studies have been conducted to determine the optimal strategy for intraoperative fluid replacement therapy in renal transplantation surgery. Since infusion of sodium bicarbonate as a buffer seems to be safer than other buffer compounds (lactate, gluconate, acetatethat indirectly convert into it within the liver, We hypothesized tight control of metabolic acidosis by infusion of sodium bicarbonate may improve early post-operative renal function in renal transplant recipients. Methods:120 patients were randomly divided into two equal groups. In group A, bicarbonate was infused intra-operatively according to Base Excess (BE measurements to achieve the normal values of BE (5 to +5 mEq/L. In group B, infusion of bicarbonate was allowed only in case of severe metabolic acidosis (BE [less than or equal to] 15 mEq/L or bicarbonate [less than or equal to] 10 mEq/L or PH [less than or equal to] 7.15. Minute ventilation was adjusted to keep PaCO2 within the normal range. Primary end-point was sampling of serum creatinine level in first, second, third and seventh post-operative days for statistical comparison between groups. Secondary objectives were comparison of cumulative urine volumes in the first 24 h of post-operative period and serum BUN levels which were obtained in first, second, third and seventh post-operative days. Results:In group A, all of consecutive serum creatinine levels were significantly lower in comparison with group B. With regard to secondary outcomes, no significant difference between groups was observed. Conclusion:Intra-operative tight control of metabolic acidosis by infusion of Sodium Bicarbonate in renal transplant recipients may improve early post-operative renal function.

  8. Effects of tight versus non tight control of metabolic acidosis on early renal function after kidney transplantation

    Etezadi Farhad

    2012-09-01

    Full Text Available Abstract Background Recently, several studies have been conducted to determine the optimal strategy for intra-operative fluid replacement therapy in renal transplantation surgery. Since infusion of sodium bicarbonate as a buffer seems to be safer than other buffer compounds (lactate, gluconate, acetatethat indirectly convert into it within the liver, We hypothesized tight control of metabolic acidosis by infusion of sodium bicarbonate may improve early post-operative renal function in renal transplant recipients. Methods 120 patients were randomly divided into two equal groups. In group A, bicarbonate was infused intra-operatively according to Base Excess (BE measurements to achieve the normal values of BE (−5 to +5 mEq/L. In group B, infusion of bicarbonate was allowed only in case of severe metabolic acidosis (BE ≤ −15 mEq/L or bicarbonate ≤ 10 mEq/L or PH ≤ 7.15. Minute ventilation was adjusted to keep PaCO2 within the normal range. Primary end-point was sampling of serum creatinine level in first, second, third and seventh post-operative days for statistical comparison between groups. Secondary objectives were comparison of cumulative urine volumes in the first 24 h of post-operative period and serum BUN levels which were obtained in first, second, third and seventh post-operative days. Results In group A, all of consecutive serum creatinine levels were significantly lower in comparison with group B. With regard to secondary outcomes, no significant difference between groups was observed. Conclusion Intra-operative tight control of metabolic acidosis by infusion of Sodium Bicarbonate in renal transplant recipients may improve early post-operative renal function.

  9. Single-walled carbon nanotubes disturbed the immune and metabolic regulation function 13-weeks after a single intratracheal instillation

    Park, Eun-Jung, E-mail: pejtoxic@hanmail.net [Myunggok Eye Research Institute, Konyang University, Daejeon 302-718 (Korea, Republic of); Hong, Young-Shick [Division of Food and Nutrition, Chonnam National University, Yongbong-Ro, Buk-Gu, Gwangju 500-757 (Korea, Republic of); Lee, Byoung-Seok [Toxicologic Pathology Center, Korea Institute of Toxicology, Daejeon (Korea, Republic of); Yoon, Cheolho [Seoul Center, Korea Basic Science Institute, Seoul 126-16 (Korea, Republic of); Jeong, Uiseok; Kim, Younghun [Department of Chemical Engineering, Kwangwoon University, Seoul 139-701 (Korea, Republic of)

    2016-07-15

    Due to their unique physicochemical properties, the potential health effects of single-walled carbon nanotubes (SWCNTs) have attracted continuous attention together with their extensive application. In this study, we aimed to identify local and systemic health effects following pulmonary persistence of SWCNTs. As expected, SWCNTs remained in the lung for 13 weeks after a single intratracheal instillation (50, 100, and 200 μg/kg). In the lung, the total number of cells and the percentages of lymphocytes and neutrophils significantly increased at 200 μg/kg compared to the control, and the Th1-polarized immune response was induced accompanying enhanced expression of tissue damage-related genes and increased release of chemokines. Additionally, SWCNTs enhanced the expression of antigen presentation-related proteins on the surface of antigen-presenting cells, however, maturation of dendritic cells was inhibited by their persistence. As compared to the control, a significant increase in the percentage of neutrophils and a remarkable decrease of BUN and potassium level were observed in the blood of mice treated with the highest dose. This was accompanied by the down-regulation of the expression of antigen presentation-related proteins on splenocytes. Moreover, protein and glucose metabolism were disturbed with an up-regulation of fatty acid β-oxidation. Taken together, we conclude that SWCNTs may induce adverse health effects by disturbing immune and metabolic regulation functions in the body. Therefore, careful application of SWCNTs is necessary for the enforcement of safety in nano-industries. - Highlights: • We evaluated local and systemic health effects following persistence of SWCNTs. • SWCNTs remained in the lung for 13 weeks after a single intratracheal instillation. • Th1-polarized immune response was induced in the lung. • The expression of antigen presentation-related proteins was altered. • Immune and metabolic regulation function were disturbed.

  10. Functional relationships between plasmids and their significance for metabolism and symbiotic performance of Rhizobium leguminosarum bv. trifolii.

    Stasiak, Grażyna; Mazur, Andrzej; Wielbo, Jerzy; Marczak, Małgorzata; Zebracki, Kamil; Koper, Piotr; Skorupska, Anna

    2014-11-01

    Rhizobium leguminosarum bv. trifolii TA1 (RtTA1) is a soil bacterium establishing a highly specific symbiotic relationship with clover, which is based on the exchange of molecular signals between the host plant and the microsymbiont. The RtTA1 genome is large and multipartite, composed of a chromosome and four plasmids, which comprise approximately 65 % and 35 % of the total genome, respectively. Extrachromosomal replicons were previously shown to confer significant metabolic versatility to bacteria, which is important for their adaptation in the soil and nodulation competitiveness. To investigate the contribution of individual RtTA1 plasmids to the overall cell phenotype, metabolic properties and symbiotic performance, a transposon-based elimination strategy was employed. RtTA1 derivatives cured of pRleTA1b or pRleTA1d and deleted in pRleTA1a were obtained. In contrast to the in silico predictions of pRleTA1b and pRleTA1d, which were described as chromid-like replicons, both appeared to be completely curable. On the other hand, for pRleTA1a (symbiotic plasmid) and pRleTA1c, which were proposed to be unessential for RtTA1 viability, it was not possible to eliminate them at all (pRleTA1c) or entirely (pRleTA1a). Analyses of the phenotypic traits of the RtTA1 derivatives obtained revealed the functional significance of individual plasmids and their indispensability for growth, certain metabolic pathways, production of surface polysaccharides, autoaggregation, biofilm formation, motility and symbiotic performance. Moreover, the results allow us to suggest broad functional cooperation among the plasmids in shaping the phenotypic properties and symbiotic capabilities of rhizobia.

  11. Preliminary evaluation of MRI-derived input function for quantitative measurement of glucose metabolism in an integrated PET-MRI

    Anazodo, Udunna; Kewin, Matthew [Lawson Health Research Institute, Department of Medical Biophysics, Western University, London, Ontario (Canada); Finger, Elizabeth [Department of Clinical Neurological Sciences, Western University, London, Ontario (Canada); Thiessen, Jonathan; Hadway, Jennifer; Butler, John [Lawson Health Research Institute, Department of Medical Biophysics, Western University, London, Ontario (Canada); Pavlosky, William [Diagnostic Imaging, St Joseph' s Health Care, London, Ontario (Canada); Prato, Frank; Thompson, Terry; St Lawrence, Keith [Lawson Health Research Institute, Department of Medical Biophysics, Western University, London, Ontario (Canada)

    2015-05-18

    PET semi-quantitative methods such as relative uptake value can be robust but offer no biological information and do not account for intra-subject variability in tracer administration or clearance. Simultaneous multimodal measurements that combine PET and MRI not only permit crucial multiparametric measurements, it provides means of applying tracer kinetic modelling without the need for serial arterial blood sampling. In this study we adapted an image-derived input function (IDIF) method to improve characterization of glucose metabolism in an ongoing dementia study. Here we present preliminary results in a small group of frontotemporal dementia patients and controls. IDIF was obtained directly from dynamic PET data guided by regions of interest drawn on carotid vessels on high resolution T1-weighted MR Images. IDIF was corrected for contamination of non-arterial voxels. A validation of the method was performed in a porcine model in a PET-CT scanner comparing IDIF to direct arterial blood samples. Metabolic rate of glucose (CMRglc) was measured voxel-by-voxel in gray matter producing maps that were compared between groups. Net influx rate (Ki) and global mean CMRglc are reported. A good correlation (r = 0.9 p<0.0001) was found between corrected IDIF and input function measured from direct arterial blood sampling in the validation study. In 3 FTD and 3 controls, a trend towards hypometabolism was found in frontal, temporal and parietal lobes similar to significant differences previously reported by other groups. The global mean CMRglc and Ki observed in control subjects are in line with previous reports. In general, kinetic modelling of PET-FDG using an MR-IDIF can improve characterization of glucose metabolism in dementia. This method is feasible in multimodal studies that aim to combine PET molecular imaging with MRI as dynamic PET can be acquired along with multiple MRI measurements.

  12. Vitamin A Metabolism: An Update

    William S. Blaner

    2011-01-01

    Full Text Available Retinoids are required for maintaining many essential physiological processes in the body, including normal growth and development, normal vision, a healthy immune system, normal reproduction, and healthy skin and barrier functions. In excess of 500 genes are thought to be regulated by retinoic acid. 11-cis-retinal serves as the visual chromophore in vision. The body must acquire retinoid from the diet in order to maintain these essential physiological processes. Retinoid metabolism is complex and involves many different retinoid forms, including retinyl esters, retinol, retinal, retinoic acid and oxidized and conjugated metabolites of both retinol and retinoic acid. In addition, retinoid metabolism involves many carrier proteins and enzymes that are specific to retinoid metabolism, as well as other proteins which may be involved in mediating also triglyceride and/or cholesterol metabolism. This review will focus on recent advances for understanding retinoid metabolism that have taken place in the last ten to fifteen years.

  13. Carotenoid metabolic profiling and transcriptome-genome mining reveal functional equivalence among blue-pigmented copepods and appendicularia

    Mojib, Nazia; Amad, Maan H.; Thimma, Manjula; Aldanondo, Naroa; Kumaran, Mande; Irigoien, Xabier

    2014-01-01

    The tropical oligotrophic oceanic areas are characterized by high water transparency and annual solar radiation. Under these conditions, a large number of phylogenetically diverse mesozooplankton species living in the surface waters (neuston) are found to be blue pigmented. In the present study, we focused on understanding the metabolic and genetic basis of the observed blue phenotype functional equivalence between the blue-pigmented organisms from the phylum Arthropoda, subclass Copepoda (Acartia fossae) and the phylum Chordata, class Appendicularia (Oikopleura dioica) in the Red Sea. Previous studies have shown that carotenoid–protein complexes are responsible for blue coloration in crustaceans. Therefore, we performed carotenoid metabolic profiling using both targeted and nontargeted (high-resolution mass spectrometry) approaches in four different blue-pigmented genera of copepods and one blue-pigmented species of appendicularia. Astaxanthin was found to be the principal carotenoid in all the species. The pathway analysis showed that all the species can synthesize astaxanthin from β-carotene, ingested from dietary sources, via 3-hydroxyechinenone, canthaxanthin, zeaxanthin, adonirubin or adonixanthin. Further, using de novo assembled transcriptome of blue A. fossae (subclass Copepoda), we identified highly expressed homologous β-carotene hydroxylase enzymes and putative carotenoid-binding proteins responsible for astaxanthin formation and the blue phenotype. In blue O. dioica (class Appendicularia), corresponding putative genes were identified from the reference genome. Collectively, our data provide molecular evidences for the bioconversion and accumulation of blue astaxanthin–protein complexes underpinning the observed ecological functional equivalence and adaptive convergence among neustonic mesozooplankton.

  14. Carotenoid metabolic profiling and transcriptome-genome mining reveal functional equivalence among blue-pigmented copepods and appendicularia

    Mojib, Nazia

    2014-06-01

    The tropical oligotrophic oceanic areas are characterized by high water transparency and annual solar radiation. Under these conditions, a large number of phylogenetically diverse mesozooplankton species living in the surface waters (neuston) are found to be blue pigmented. In the present study, we focused on understanding the metabolic and genetic basis of the observed blue phenotype functional equivalence between the blue-pigmented organisms from the phylum Arthropoda, subclass Copepoda (Acartia fossae) and the phylum Chordata, class Appendicularia (Oikopleura dioica) in the Red Sea. Previous studies have shown that carotenoid–protein complexes are responsible for blue coloration in crustaceans. Therefore, we performed carotenoid metabolic profiling using both targeted and nontargeted (high-resolution mass spectrometry) approaches in four different blue-pigmented genera of copepods and one blue-pigmented species of appendicularia. Astaxanthin was found to be the principal carotenoid in all the species. The pathway analysis showed that all the species can synthesize astaxanthin from β-carotene, ingested from dietary sources, via 3-hydroxyechinenone, canthaxanthin, zeaxanthin, adonirubin or adonixanthin. Further, using de novo assembled transcriptome of blue A. fossae (subclass Copepoda), we identified highly expressed homologous β-carotene hydroxylase enzymes and putative carotenoid-binding proteins responsible for astaxanthin formation and the blue phenotype. In blue O. dioica (class Appendicularia), corresponding putative genes were identified from the reference genome. Collectively, our data provide molecular evidences for the bioconversion and accumulation of blue astaxanthin–protein complexes underpinning the observed ecological functional equivalence and adaptive convergence among neustonic mesozooplankton.

  15. Functioning of Microsomal Cytochrome P450s: Murburn Concept Explains the Metabolism of Xenobiotics in Hepatocytes.

    Manoj, Kelath Murali; Parashar, Abhinav; Gade, Sudeep K; Venkatachalam, Avanthika

    2016-01-01

    Using oxygen and NADPH, the redox enzymes cytochrome P450 (CYP) and its reductase (CPR) work in tandem to carry out the phase I metabolism of a vast majority of drugs and xenobiotics. As per the erstwhile understanding of the catalytic cycle, binding of the substrate to CYP's heme distal pocket allows CPR to pump electrons through a CPR-CYP complex. In turn, this trigger (a thermodynamic push of electrons) leads to the activation of oxygen at CYP's heme-center, to give Compound I, a two-electron deficient enzyme reactive intermediate. The formation of diffusible radicals and reactive oxygen species (DROS, hitherto considered an undesired facet of the system) was attributed to the heme-center. Recently, we had challenged these perceptions and proposed the murburn ("mured burning" or "mild unrestricted burning") concept to explain heme enzymes' catalytic mechanism, electron-transfer phenomena and the regulation of redox equivalents' consumption. Murburn concept incorporates a one-electron paradigm, advocating obligatory roles for DROS. The new understanding does not call for high-affinity substrate-binding at the heme distal pocket of the CYP (the first and the most crucial step of the erstwhile paradigm) or CYP-CPR protein-protein complexations (the operational backbone of the erstwhile cycle). Herein, the dynamics of reduced nicotinamide nucleotides' consumption, peroxide formation and depletion, product(s) formation, etc. was investigated with various controls, by altering reaction variables, environments and through the incorporation of diverse molecular probes. In several CYP systems, control reactions lacking the specific substrate showed comparable or higher peroxide in milieu, thereby discrediting the foundations of the erstwhile hypothesis. The profiles obtained by altering CYP:CPR ratios and the profound inhibitions observed upon the incorporation of catalytic amounts of horseradish peroxidase confirm the obligatory roles of DROS in milieu, ratifying

  16. Burke-Fahn-Marsden dystonia severity, Gross Motor, Manual Ability, and Communication Function Classification scales in childhood hyperkinetic movement disorders including cerebral palsy: a 'Rosetta Stone' study.

    Elze, Markus C; Gimeno, Hortensia; Tustin, Kylee; Baker, Lesley; Lumsden, Daniel E; Hutton, Jane L; Lin, Jean-Pierre S-M

    2016-02-01

    Hyperkinetic movement disorders (HMDs) can be assessed using impairment-based scales or functional classifications. The Burke-Fahn-Marsden Dystonia Rating Scale-movement (BFM-M) evaluates dystonia impairment, but may not reflect functional ability. The Gross Motor Function Classification System (GMFCS), Manual Ability Classification System (MACS), and Communication Function Classification System (CFCS) are widely used in the literature on cerebral palsy to classify functional ability, but not in childhood movement disorders. We explore the concordance of these three functional scales in a large sample of paediatric HMDs and the impact of dystonia severity on these scales. Children with HMDs (n=161; median age 10y 3mo, range 2y 6mo-21y) were assessed using the BFM-M, GMFCS, MACS, and CFCS from 2007 to 2013. This cross-sectional study contrasts the information provided by these scales. All four scales were strongly associated (all Spearman's rank correlation coefficient rs >0.72, pdisorders including cerebral palsy can be effectively evaluated using these scales. © 2015 Mac Keith Press.

  17. Effect of STA-proximal MCA bypass. Improvement of cerebral blood flow and metabolism and neuropsychological function

    Ogawa, Akira; Funayama, Masayuki; Miura, Kazuyuki; Ogasawara, Kuniaki; Suzuki, Michiyasu; Kuroda, Kiyoshi; Sasaki, Toshiaki [Iwate Medical Univ., Morioka (Japan). School of Medicine

    1998-11-01

    We investigated cerebral blood flow (CBF) and metabolism in patients with hemodynamic ischemia by positron emission tomography (PET) and thermal diffusion flow meter. We also studied neuropsychological functions to evaluate the effects of surgical revascularization. Bypass surgery of the superficial temporal artery to the proximal middle cerebral artery was performed on 26 patients satisfying the following categories: stenosis or occlusive lesion in main cerebral arteries; no marked focus of infarction on CT or MRI. PET was performed before and 1 month after the operation, and CBF, the cerebral metabolic rate of oxygen (CMRO{sub 2}) and oxygen extraction fraction (OEF) were analyzed. Cerebrovascular reserve capacity (CVRC) was also calculated after acetazolamide challenge. CBF during the operation was continuously measured with a thermal diffusion flow meter. CO{sub 2} response of CBF was analyzed before and after anastomosis. Neuropsychological functions were evaluated by Hasegawa dementia scale revised (HDS-R), mini-mental state examination (MMSE) and Wechsler adult intelligence scale revised (WAIS-R). Before the operation, increase in OEF accorded with the decrease in CBF, and a significant relationship between both CBF and CVRC, and OEF and CVRC was found. A decrease in CVRC was noted prior to a decrease in CBF and elevation of OEF. CVRC caused by acetazolamide might reflect CO{sub 2} reactivity. Significant improvement of CBF and CVRC, and normalization of OEF were observed after the operation. Also, significant improvement of neuropsychological function was observed by HDS-R and WAIS-R. Disturbance in neuropsychological function might reflect elevation of OEF. (author)

  18. Pseudomonas putida as a functional chassis for industrial biocatalysis: From native biochemistry to trans-metabolism

    Nikel, Pablo I.; de Lorenzo, Víctor

    2018-01-01

    are presented for substantiating the worth of P. putida as one of the favorite workhorses for sustainable manufacturing of fine and bulk chemicals in the current times of the 4th Industrial Revolution. The potential of P. putida to extend its rich native biochemistry beyond existing boundaries is discussed...... biochemistry is naturally geared to generate reductive currency [i.e., NAD(P)H] that makes this bacterium a phenomenal host for redox-intensive reactions. In some cases, genetic editing of the indigenous biochemical network of P. putida (cis-metabolism) has sufficed to obtain target compounds of industrial...... stresses. Over the years, these properties have been capitalized biotechnologically owing to the expanding wealth of genetic tools designed for deep-editing the P. putida genome. A suite of dedicated vectors inspired in the core tenets of synthetic biology have enabled to suppress many of the naturally...

  19. Functional analysis of lipid metabolism genes in wine yeasts during alcoholic fermentation at low temperature.

    López-Malo, María; García-Ríos, Estéfani; Chiva, Rosana; Guillamon, José M

    2014-10-29

    Wine produced by low-temperature fermentation is mostly considered to have improved sensory qualities. However few commercial wine strains available on the market are well-adapted to ferment at low temperature (10 - 15°C). The lipid metabolism of Saccharomyces cerevisiae plays a central role in low temperature adaptation. One strategy to modify lipid composition is to alter transcriptional activity by deleting or overexpressing the key genes of lipid metabolism. In a previous study, we identified the genes of the phospholipid, sterol and sphingolipid pathways, which impacted on growth capacity at low temperature. In the present study, we aimed to determine the influence of these genes on fermentation performance and growth during low-temperature wine fermentations. We analyzed the phenotype during fermentation at the low and optimal temperature of the lipid mutant and overexpressing strains in the background of a derivative commercial wine strain. The increase in the gene dosage of some of these lipid genes, e.g., PSD1 , LCB3, DPL1 and OLE1, improved fermentation activity during low-temperature fermentations, thus confirming their positive role during wine yeast adaptation to cold. Genes whose overexpression improved fermentation activity at 12°C were overexpressed by chromosomal integration into commercial wine yeast QA23. Fermentations in synthetic and natural grape must were carried out by this new set of overexpressing strains. The strains overexpressing OLE1 and DPL1 were able to finish fermentation before commercial wine yeast QA23. Only the OLE1 gene overexpression produced a specific aroma profile in the wines produced with natural grape must.

  20. Functional analysis of lipid metabolism genes in wine yeasts during alcoholic fermentation at low temperature

    María López-Malo

    2014-10-01

    Full Text Available Wine produced by low-temperature fermentation is mostly considered to have improved sensory qualities. However few commercial wine strains available on the market are well-adapted to ferment at low temperature (10 – 15°C. The lipid metabolism of Saccharomyces cerevisiae plays a central role in low temperature adaptation. One strategy to modify lipid composition is to alter transcriptional activity by deleting or overexpressing the key genes of lipid metabolism. In a previous study, we identified the genes of the phospholipid, sterol and sphingolipid pathways, which impacted on growth capacity at low temperature. In the present study, we aimed to determine the influence of these genes on fermentation performance and growth during low-temperature wine fermentations. We analyzed the phenotype during fermentation at the low and optimal temperature of the lipid mutant and overexpressing strains in the background of a derivative commercial wine strain. The increase in the gene dosage of some of these lipid genes, e.g., PSD1, LCB3, DPL1 and OLE1, improved fermentation activity during low-temperature fermentations, thus confirming their positive role during wine yeast adaptation to cold. Genes whose overexpression improved fermentation activity at 12°C were overexpressed by chromosomal integration into commercial wine yeast QA23. Fermentations in synthetic and natural grape must were carried out by this new set of overexpressing strains. The strains overexpressing OLE1 and DPL1 were able to finish fermentation before commercial wine yeast QA23. Only the OLE1 gene overexpression produced a specific aroma profile in the wines produced with natural grape must.

  1. Injury timing alters metabolic, inflammatory and functional outcomes following repeated mild traumatic brain injury.

    Weil, Zachary M; Gaier, Kristopher R; Karelina, Kate

    2014-10-01

    Repeated head injuries are a major public health concern both for athletes, and members of the police and armed forces. There is ample experimental and clinical evidence that there is a period of enhanced vulnerability to subsequent injury following head trauma. Injuries that occur close together in time produce greater cognitive, histological, and behavioral impairments than do injuries separated by a longer period. Traumatic brain injuries alter cerebral glucose metabolism and the resolution of altered glucose metabolism may signal the end of the period of greater vulnerability. Here, we injured mice either once or twice separated by three or 20days. Repeated injuries that were separated by three days were associated with greater axonal degeneration, enhanced inflammatory responses, and poorer performance in a spatial learning and memory task. A single injury induced a transient but marked increase in local cerebral glucose utilization in the injured hippocampus and sensorimotor cortex, whereas a second injury, three days after the first, failed to induce an increase in glucose utilization at the same time point. In contrast, when the second injury occurred substantially later (20days after the first injury), an increase in glucose utilization occurred that paralleled the increase observed following a single injury. The increased glucose utilization observed after a single injury appears to be an adaptive component of recovery, while mice with 2 injuries separated by three days were not able to mount this response, thus this second injury may have produced a significant energetic crisis such that energetic demands outstripped the ability of the damaged cells to utilize energy. These data strongly reinforce the idea that too rapid return to activity after a traumatic brain injury can induce permanent damage and disability, and that monitoring cerebral energy utilization may be a tool to determine when it is safe to return to the activity that caused the initial

  2. Fagus sylvatica L. provenances maintain different leaf metabolic profiles and functional response

    Aranda, Ismael; Sánchez-Gómez, David; de Miguel, Marina; Mancha, Jose Antonio; Guevara, María Angeles; Cadahía, Estrella; Fernández de Simón, María Brígida

    2017-07-01

    Most temperate forest tree species will suffer important environmental changes as result of the climate change. Adaptiveness to local conditions could change at different sites in the future. In this context, the study of intra-specific variability is important to clarify the singularity of different local populations. Phenotypic differentiation between three beech provenances covering a wide latitudinal range (Spain/ES, Germany/DE and Sweden/SE), was studied in a greenhouse experiment. Non-target leaf metabolite profiles and ecophysiological response was analyzed in well-watered and water stressed seedlings. There was a provenance-specific pattern in the relative concentrations of some leaf metabolites regardless watering treatment. The DE and SE from the center and north of the distribution area of the species showed a clear differentiation from the ES provenance in the relative concentration of some metabolites. Thus the ES provenance from the south maintained larger relative concentration of some organic and amino acids (e.g. fumaric and succinic acids or valine and isoleucine), and in some secondary metabolites (e.g. kaempferol, caffeic and ferulic acids). The ecophysiological response to mild water stress was similar among the three provenances as a consequence of the moderate water stress applied to seedlings, although leaf N isotope composition (δ15N) and leaf C:N ratio were higher and lower respectively in DE than in the other two provenances. This would suggest potential differences in the capacity to uptake and post-process nitrogen according to provenance. An important focus of the study was to address for the first time inter-provenance leaf metabolic diversity in beech from a non-targeted metabolic profiling approach that allowed differentiation of the three studied provenances.

  3. Metagenome-based metabolic reconstruction reveals the ecophysiological function of Epsilonproteobacteria in a hydrocarbon-contaminated sulfidic aquifer

    Andreas Hardy Keller

    2015-12-01

    Full Text Available The population genome of an uncultured bacterium assigned to the Campylobacterales (Epsilonproteobacteria was reconstructed from a metagenome dataset obtained by whole-genome shotgun pyrosequencing. Genomic DNA was extracted from a sulfate-reducing, m-xylene-mineralizing enrichment culture isolated from groundwater of a benzene-contaminated sulfidic aquifer. The identical epsilonproteobacterial phylotype has previously been detected in toluene- or benzene-mineralizing, sulfate-reducing consortia enriched from the same site. Previous stable isotope probing experiments with 13C6-labeled benzene suggested that this phylotype assimilates benzene-derived carbon in a syntrophic benzene-mineralizing consortium that uses sulfate as terminal electron acceptor. However, the type of energy metabolism and the ecophysiological function of this epsilonproteobacterium within aromatic hydrocarbon-degrading consortia and in the sulfidic aquifer are poorly understood.Annotation of the epsilonproteobacterial population genome suggests that the bacterium plays a key role in sulfur cycling as indicated by the presence of a sqr gene encoding a sulfide quinone oxidoreductase and psr genes encoding a polysulfide reductase. It may gain energy by using sulfide or hydrogen/formate as electron donors. Polysulfide, fumarate, as well as oxygen are potential electron acceptors. Auto- or mixotrophic carbon metabolism seems plausible since a complete reductive citric acid cycle was detected. Thus the bacterium can thrive in pristine groundwater as well as in hydrocarbon-contaminated aquifers. In hydrocarbon-contaminated sulfidic habitats, the epsilonproteobacterium may generate energy by coupling the oxidation of hydrogen or formate and highly abundant sulfide with the reduction of fumarate and/or polysulfide, accompanied by efficient assimilation of acetate produced during fermentation or incomplete oxidation of hydrocarbons. The highly efficient assimilation of acetate was

  4. Metagenome-Based Metabolic Reconstruction Reveals the Ecophysiological Function of Epsilonproteobacteria in a Hydrocarbon-Contaminated Sulfidic Aquifer.

    Keller, Andreas H; Schleinitz, Kathleen M; Starke, Robert; Bertilsson, Stefan; Vogt, Carsten; Kleinsteuber, Sabine

    2015-01-01

    The population genome of an uncultured bacterium assigned to the Campylobacterales (Epsilonproteobacteria) was reconstructed from a metagenome dataset obtained by whole-genome shotgun pyrosequencing. Genomic DNA was extracted from a sulfate-reducing, m-xylene-mineralizing enrichment culture isolated from groundwater of a benzene-contaminated sulfidic aquifer. The identical epsilonproteobacterial phylotype has previously been detected in toluene- or benzene-mineralizing, sulfate-reducing consortia enriched from the same site. Previous stable isotope probing (SIP) experiments with (13)C6-labeled benzene suggested that this phylotype assimilates benzene-derived carbon in a syntrophic benzene-mineralizing consortium that uses sulfate as terminal electron acceptor. However, the type of energy metabolism and the ecophysiological function of this epsilonproteobacterium within aromatic hydrocarbon-degrading consortia and in the sulfidic aquifer are poorly understood. Annotation of the epsilonproteobacterial population genome suggests that the bacterium plays a key role in sulfur cycling as indicated by the presence of an sqr gene encoding a sulfide quinone oxidoreductase and psr genes encoding a polysulfide reductase. It may gain energy by using sulfide or hydrogen/formate as electron donors. Polysulfide, fumarate, as well as oxygen are potential electron acceptors. Auto- or mixotrophic carbon metabolism seems plausible since a complete reductive citric acid cycle was detected. Thus the bacterium can thrive in pristine groundwater as well as in hydrocarbon-contaminated aquifers. In hydrocarbon-contaminated sulfidic habitats, the epsilonproteobacterium may generate energy by coupling the oxidation of hydrogen or formate and highly abundant sulfide with the reduction of fumarate and/or polysulfide, accompanied by efficient assimilation of acetate produced during fermentation or incomplete oxidation of hydrocarbons. The highly efficient assimilation of acetate was recently

  5. Aspects of astrocyte energy metabolism, amino acid neurotransmitter homoeostasis and metabolic compartmentation

    Kreft, Marko; Bak, Lasse Kristoffer; Waagepetersen, Helle S

    2012-01-01

    Astrocytes are key players in brain function; they are intimately involved in neuronal signalling processes and their metabolism is tightly coupled to that of neurons. In the present review, we will be concerned with a discussion of aspects of astrocyte metabolism, including energy......-generating pathways and amino acid homoeostasis. A discussion of the impact that uptake of neurotransmitter glutamate may have on these pathways is included along with a section on metabolic compartmentation....

  6. Effect of Functional Bread Rich in Potassium, γ-Aminobutyric Acid and Angiotensin-Converting Enzyme Inhibitors on Blood Pressure, Glucose Metabolism and Endothelial Function

    Becerra-Tomás, Nerea; Guasch-Ferré, Marta; Quilez, Joan; Merino, Jordi; Ferré, Raimon; Díaz-López, Andrés; Bulló, Mònica; Hernández-Alonso, Pablo; Palau-Galindo, Antoni; Salas-Salvadó, Jordi

    2015-01-01

    Abstract Because it has been suggested that food rich in γ-aminobutyric acid (GABA) or angiotensin-converting enzyme inhibitor (ACEI) peptides have beneficial effects on blood pressure (BP) and other cardiovascular risk factors, we tested the effects of low-sodium bread, but rich in potassium, GABA, and ACEI peptides on 24-hour BP, glucose metabolism, and endothelial function. A randomized, double-blind, crossover trial was conducted in 30 patients with pre or mild-to-moderate hypertension, comparing three 4-week nutritional interventions separated by 2-week washout periods. Patients were randomly assigned to consume 120 g/day of 1 of the 3 types of bread for each nutritional intervention: conventional wheat bread (CB), low-sodium wheat bread enriched in potassium (LSB), and low-sodium wheat bread rich in potassium, GABA, and ACEI peptides (LSB + G). For each period, 24-hour BP measurements, in vivo endothelial function, and biochemical samples were obtained. After LSB + G consumption, 24-hour ambulatory BP underwent a nonsignificant greater reduction than after the consumption of CB and LSB (0.26 mm Hg in systolic BP and −0.63 mm Hg in diastolic BP for CB; −0.71 mm Hg in systolic BP and −1.08 mm Hg in diastolic BP for LSB; and −0.75 mm Hg in systolic BP and −2.12 mm Hg in diastolic BP for LSB + G, respectively). Diastolic BP at rest decreased significantly during the LSB + G intervention, although there were no significant differences in changes between interventions. There were no significant differences between interventions in terms of changes in in vivo endothelial function, glucose metabolism, and peripheral inflammatory parameters. Compared with the consumption of CB or LSB, no greater beneficial effects on 24-hour BP, endothelial function, or glucose metabolism were demonstrated after the consumption of LSB + G in a population with pre or mild-to-moderate hypertension. Further studies are warranted to clarify the

  7. FSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Guidance on the scientific requirements for health claims related to functions of the ne rvous system, including psycholog ical functions

    Tetens, Inge

    The European Food Safety Authority (EFSA) asked the Panel on Dietetic Products, Nutrition and Allergies to draft guidance on scientific requirements for health claims related to functions of the nervous system, including psychological functions. This guidance has been drawn from scientific opinions......, and was released for public consultation from 17 October 2011 to 16 December 2011....

  8. Renal and adrenal function in patients with metabolic syndrome and type 2 diabetes mellitus

    Ribal'chenko, V.M.; Zubkova, G.A.; Luchits'kij, Je.V.; Luchits'kij, V.Je.; Markov, V.V.; Sologub, N.V.

    2009-01-01

    Dynamic kidney scan with diethylene-triamine-pentaacetate labeled with 99m Tc demonstrated that disorders of filtration-excretion function of the kidneys correlated with the changes in the level of adrenal hormones.

  9. Analysis of glucose metabolism in patients with diabetes mellitus by using functional images derived from 18F-FDG PET

    Ohtake, Tohru; Yokoyama, Ikuo; Watanabe, Toshiaki; Kosaka, Noboru; Momose, Toshimitsu; Nishikawa, Jun-ichi; Serizawa, Takashi; Sasaki, Yasuhito

    1993-01-01

    Functional images of K complex (KC) and regional myocardial glucose utilization rates (rMGU), derived from F-18-fluoro-deoxy-glucose (F-18-FDG) positron emission computed tomography, were prepared. Using functional images obtained, myocardial glucose metabolism was examined in the fasting state, oral glucose loading (OG), and insulin clamp (IC) condition. The subjects were 10 patients with diabetes mellitus (DM), consisting of 8 with non-insulin dependent DM and 2 with insulin dependent DM, and 4 normal persons. Image quality, derived from both OG and IC approaches, was favorable in the normal group. In the groups of non-insulin dependent DM and insulin dependent DM patients, however, image quality was good with IC method but not with OG method. In the group of non-insulin dependent DM, rMGU derived by IC method was relatively high, but was significantly lower than that in the control group, suggesting a decreased function in glucose transporter. When using OG method, rMGU was even more decreased due to high blood sugar and low insulin. In the group of insulin dependent DM, both IC and OG approaches achieved the same rMGU as that in the control group, with the exception of KC derived by OG method that was decreased due to high blood sugar. In moderate or severe DM, myocardial viability seems to be difficult to evaluate because F-18-FDG uptake is decreased in the ischemic area associated with fasting high blood sugar. Mismatching between blood flow and metabolism is also difficult to detect due to high insulin or glucose load. Thus, myocardial viability should be evaluated in the condition of slightly loaded insulin by decreasing blood sugar. (N.K.)

  10. The Microbiome, Intestinal Function, and Arginine Metabolism of Healthy Indian Women Are Different from Those of American and Jamaican Women.

    Kao, Christina C; Cope, Julia L; Hsu, Jean W; Dwarkanath, Pratibha; Karnes, Jeffrey M; Luna, Ruth A; Hollister, Emily B; Thame, Minerva M; Kurpad, Anura V; Jahoor, Farook

    2016-03-09

    Indian women have slower arginine flux during pregnancy compared with American and Jamaican women. Arginine is a semi-essential amino acid that becomes essential during periods of rapid lean tissue deposition. It is synthesized only from citrulline, a nondietary amino acid produced mainly in the gut. The gut is therefore a key site of arginine and citrulline metabolism, and gut microbiota may affect their metabolism. The objective of this study was to identify differences in the gut microbiota of nonpregnant American, Indian, and Jamaican women and characterize the relations between the gut microbiota, gut function, and citrulline and arginine metabolism. Thirty healthy American, Indian, and Jamaican women (n = 10/group), aged 28.3 ± 0.8 y, were infused intravenously with [guanidino- 15 N 2 ]arginine, [5,5- 2 H 2 ]citrulline, and [ 15 N 2 ]ornithine and given oral [U- 13 C 6 ]arginine in the fasting and postprandial states. Fecal bacterial communities were characterized by 16S rRNA gene sequencing. In the fasting state, Indian women had lower citrulline flux than did American and Jamaican women [7.0 ± 0.4 compared with 9.1 ± 0.4 and 8.9 ± 0.2 μmol ⋅ kg fat-free mass (FFM) -1  ⋅ h -1 , P = 0.01] and greater enteral arginine conversion to ornithine than did American women (1.4 ± 0.11 compared with 1.0 ± 0.08 μmol ⋅ kg FFM -1  ⋅ h -1 , P = 0.04). They also had lower mannitol excretion than American and Jamaican women (154 ± 37.1 compared with 372 ± 51.8 and 410 ± 39.6 mg/6 h, P Indian women had increased mean relative abundances of Prevotella (42%) compared to American and Jamaican women (7% and Indian women. © 2016 American Society for Nutrition.

  11. Role of serylamino as a protector against gamma rays hazards on ovarian functions, carbohydrate and lipid metabolism during meta-estrous stage in rats

    Abou-Safi, KM.

    2005-01-01

    In this study, functional investigations were performed to assess the ability of silymarin to overcome the gamma rays-induced alterations on three related pivots: 1- Ovarian functions through the pituitary-gonadal hormones [follicle stimulating hormone (FSH), estradiol (E2) and progesterone. 2- Carbohydrate metabolism through pancreatic insulin associated with blood glucose and liver glycogen content. 3- Lipid profile including triglycerides, total cholesterol, high density lipoprotein (HDL-cholesterol) and low density lipoprotein (LDL-cholesterol). Fifty female rats were divided into 4 groups: 1- Control. 2- Whole body y-irradiated (I Gy). 3- Rats orally treated with silymarin (10 mg/100 g body weight) twice daily for one week. 4- Rats received silymarin as group (3) then irradiated 2 hours after the last dose of silymarin. Samples were taken 2 hours, 2 days and 2 weeks after silyrnarin gavage (group 3) or irradiation (groups 2 and 4). The results obtained showed lowered levels of FSH, E2 and P 4 as a result of ovarian dysfunction early after 2 hours and maximized after 2 weeks in irradiated rats. Plasma insulin and glucose levels were elevated with a decrease in glycogen content in liver. Also, plasma triglycerides, total cholesterol, LDL-cholesterol were elevated concomitant with decreased HDL-cholesterol level. Silymarin succeeded to ameliorate the disorders induced by irradiation and restored the majority of disturbed levels to control range. The present study designates that silymarin has a positive prophylactic effect against radiation-induced hazard on the ovarian function and speculates that silymarin could imitate a physiologic regulator for carbohydrate and lipid metabolism through several mentioned mechanisms

  12. Comparative analysis of taxonomic, functional, and metabolic patterns of microbiomes from 14 full-scale biogas reactors by metagenomic sequencing and radioisotopic analysis.

    Luo, Gang; Fotidis, Ioannis A; Angelidaki, Irini

    2016-01-01

    Biogas production is a very complex process due to the high complexity in diversity and interactions of the microorganisms mediating it, and only limited and diffuse knowledge exists about the variation of taxonomic and functional patterns of microbiomes across different biogas reactors, and their relationships with the metabolic patterns. The present study used metagenomic sequencing and radioisotopic analysis to assess the taxonomic, functional, and metabolic patterns of microbiomes from 14 full-scale biogas reactors operated under various conditions treating either sludge or manure. The results from metagenomic analysis showed that the dominant methanogenic pathway revealed by radioisotopic analysis was not always correlated with the taxonomic and functional compositions. It was found by radioisotopic experiments that the aceticlastic methanogenic pathway was dominant, while metagenomics analysis showed higher relative abundance of hydrogenotrophic methanogens. Principal coordinates analysis showed the sludge-based samples were clearly distinct from the manure-based samples for both taxonomic and functional patterns, and canonical correspondence analysis showed that the both temperature and free ammonia were crucial environmental variables shaping the taxonomic and functional patterns. The study further the overall patterns of functional genes were strongly correlated with overall patterns of taxonomic composition across different biogas reactors. The discrepancy between the metabolic patterns determined by metagenomic analysis and metabolic pathways determined by radioisotopic analysis was found. Besides, a clear correlation between taxonomic and functional patterns was demonstrated for biogas reactors, and also the environmental factors that shaping both taxonomic and functional genes patterns were identified.

  13. Enhanced Neuroplasticity by the Metabolic Enhancer Piracetam Associated with Improved Mitochondrial Dynamics and Altered Permeability Transition Pore Function

    Carola Stockburger

    2016-01-01

    Full Text Available The mitochondrial cascade hypothesis of dementia assumes mitochondrial dysfunction leading to reduced energy supply, impaired neuroplasticity, and finally cell death as one major pathomechanism underlying the continuum from brain aging over mild cognitive impairment to initial and advanced late onset Alzheimer’s disease. Accordingly, improving mitochondrial function has become an important strategy to treat the early stages of this continuum. The metabolic enhancer piracetam has been proposed as possible prototype for those compounds by increasing impaired mitochondrial function and related aspects like mechanisms of neuroplasticity. We here report that piracetam at therapeutically relevant concentrations improves neuritogenesis in the human cell line SH-SY5Y over conditions mirroring the whole spectrum of age-associated cognitive decline. These effects go parallel with improvement of impaired mitochondrial dynamics shifting back fission and fusion balance to the energetically more favorable fusion site. Impaired fission and fusion balance can also be induced by a reduction of the mitochondrial permeability transition pore (mPTP function as atractyloside which indicates the mPTP has similar effects on mitochondrial dynamics. These changes are also reduced by piracetam. These findings suggest the mPTP as an important target for the beneficial effects of piracetam on mitochondrial function.

  14. The metabolic enhancer piracetam ameliorates the impairment of mitochondrial function and neurite outgrowth induced by beta-amyloid peptide.

    Kurz, C; Ungerer, I; Lipka, U; Kirr, S; Schütt, T; Eckert, A; Leuner, K; Müller, W E

    2010-05-01

    beta-Amyloid peptide (Abeta) is implicated in the pathogenesis of Alzheimer's disease by initiating a cascade of events from mitochondrial dysfunction to neuronal death. The metabolic enhancer piracetam has been shown to improve mitochondrial dysfunction following brain aging and experimentally induced oxidative stress. We used cell lines (PC12 and HEK cells) and murine dissociated brain cells. The protective effects of piracetam in vitro and ex vivo on Abeta-induced impairment of mitochondrial