Effects of Multiple Cycles of Weight Loss and Regain on the Body-Weight Regulatory System in Rats.
Abstract OBJECTIVE: We studied the effects of multiple cycles of weight loss and regain on the defended body weight in rats. METHODS: 36 male Wistar rats were divided into 3 weight-matched groups: weight cyclers (n=18), ad libitum-fed controls (n=9), and maturity controls (n=9). Cyclers underwent four rounds of 20% weight loss from 50% caloric restriction, each cycle followed by recovery to stable plateau weight on ad libitum feeding. Controls ate ad libitum. Maturity controls ate ad libitum then weight cycled the final two rounds to evaluate the effect of age in later cycles. RESULTS: Cyclers post-diet ...
Source: American Journal of Physiology. Endocrinology and Metabolism - July 19, 2019 Category: Physiology Authors: Rosenbaum JL, Frayo RS, Melhorn SJ, Cummings DE, Schur EA Tags: Am J Physiol Endocrinol Metab Source Type: research

Mechanistic inferences on metabolic dysfunction in PTSD from an integrated model and multi-omic analysis: Role of glucocorticoid receptor sensitivity.
Abstract Post-traumatic stress disorder is associated with neuroendocrine alterations and metabolic abnormalities; however, how metabolism is affected by neuroendocrine disturbances is unclear. The data from combat exposed veterans with PTSD shows increased glycolysis to lactate flux, reduced TCA cycle flux, impaired amino acid and lipid metabolism, insulin resistance, inflammation and hypersensitive HPA-axis. To analyze whether the co-occurrence of multiple metabolic abnormalities are independent, or arises from an underlying regulatory defect, we employed a systems biological approach using an integrated mathema...
Source: American Journal of Physiology. Endocrinology and Metabolism - July 19, 2019 Category: Physiology Authors: Somvanshi PR, Mellon SH, Flory JD, Abu-Amara D, Consortium PSB, Wolkowitz OM, Yehuda R, Jett M, Hood L, Marmar C, Doyle FJ Tags: Am J Physiol Endocrinol Metab Source Type: research

Transcriptomic Evidence that Cortisol Alters Perinatal Epicardial Adipose Tissue Maturation.
This study investigates the effects of cortisol on epicardial adipose tissue (EAT), a visceral fat pad associated with adverse cardiovascular conditions in adults. Pregnant ewes were treated with either 1 mg/kg/day cortisol from 115 days gestation to term and EAT collected from term fetuses (control: n=8, maternal cortisol 1 mg/kg/day: n=6). To compare the effects of cortisol to the normal maturation in EAT, we also modeled the normal changes in gene expression in EAT at the transition from in utero to postnatal life using the EAT from control fetuses and from two-week-old lambs (control: n=7).), Transcriptomic modeling wa...
Source: American Journal of Physiology. Endocrinology and Metabolism - July 19, 2019 Category: Physiology Authors: Richards EM, McElhaney E, Zeringue K, Joseph S, Keller-Wood M Tags: Am J Physiol Endocrinol Metab Source Type: research

Metabolic Control via Nutrient Sensing Mechanisms: Role of Taste Receptors and the Gut-Brain Neuroendocrine Axis.
Abstract Nutrient sensing plays an important role in ensuring that appropriate digestive or hormonal responses are elicited following the ingestion of fuel substrates. Mechanisms of nutrient sensing in the oral cavity have been fairly well-characterized and involve lingual taste receptors. These include heterodimers of G-protein coupled receptor (GPCRs) of the T1R family for sensing sweet (T1R2-T1R3) and umami (T1R1-T1R3) stimuli; the T2R family for sensing bitter stimuli; and ion channels for conferring sour and salty tastes. In recent years, several studies have revealed the existence of additional nutrient sens...
Source: American Journal of Physiology. Endocrinology and Metabolism - July 16, 2019 Category: Physiology Authors: Raka F, Farr S, Kelly J, Stoianov A, Adeli K Tags: Am J Physiol Endocrinol Metab Source Type: research

Tracking adiponectin biodistribution via fluorescence molecular tomography indicates increased vascular permeability after streptozotocin-induced diabetes.
Abstract Adiponectin, highly abundant in plasma, plays an important role in mediating important beneficial effects in diabetes, inflammation and cardiovascular disease. To act on target tissues, adiponectin must move from circulation to the interstitial space, suggesting that vascular permeability plays an important role in regulating adiponectin action. To test this hypothesis, fluorescently-labelled adiponectin was used to monitor its biodistribution in mice with streptozotocin-induced diabetes (STZD). Adiponectin was indeed found to have increased sequestration in the highly fenestrated liver and other tissues ...
Source: American Journal of Physiology. Endocrinology and Metabolism - July 16, 2019 Category: Physiology Authors: Yoon N, Dadson K, Dang T, Chu T, Noskovicova N, Hinz B, Raignault A, Thorin E, Kim S, Jeon JS, Jonkman J, McKee T, Grant J, Peterson JD, Kelly SP, Sweeney G Tags: Am J Physiol Endocrinol Metab Source Type: research

Overproduction of endothelin-1 impairs glucose tolerance but does not promote visceral adipose tissue inflammation or limit metabolic adaptations to exercise.
Abstract Endothelin-1 (ET-1) is a potent vasoconstrictor and proinflammatory peptide that is upregulated in obesity. Herein, we tested the hypothesis that ET-1 signaling promotes visceral adipose tissue (AT) inflammation and disrupts glucose homeostasis. We also tested if reduced ET-1 is a required mechanism by which exercise ameliorates AT inflammation and improves glycemic control in obesity. We found that (i) diet-induced obesity, AT inflammation, and glycemic dysregulation were not accompanied by significant increased levels of ET-1 in AT or circulation in wild-type mice; and that endothelial overexpression of...
Source: American Journal of Physiology. Endocrinology and Metabolism - July 16, 2019 Category: Physiology Authors: Jurrissen TJ, Grunewald ZI, Woodford ML, Winn NC, Ball JR, Smith TN, Wheeler A, Rawlings AL, Staveley-O'Carroll KF, Ji Y, Fay WP, Paradis P, Schiffrin EL, Vieira-Potter VJ, Fadel PJ, Martinez-Lemus LA, Padilla J Tags: Am J Physiol Endocrinol Metab Source Type: research

Fetal androgen signaling defects affect β-cell mass and function, leading to glucose intolerance in high-fat diet-fed male rats.
Fetal androgen signaling defects affect β-cell mass and function, leading to glucose intolerance in high-fat diet-fed male rats. Am J Physiol Endocrinol Metab. 2019 Jul 09;: Authors: Harada N, Yotsumoto Y, Katsuki T, Yoda Y, Masuda T, Nomura M, Shiraki N, Inui H, Yamaji R Abstract We have previously demonstrated that androgen signaling expands pancreatic β-cell mass in the sexual maturation period. The aim of this study is to elucidate whether fetal androgen signaling plays important roles in β-cell mass development and β-cell function in adulthood, defects of which are associated ...
Source: American Journal of Physiology. Endocrinology and Metabolism - July 9, 2019 Category: Physiology Authors: Harada N, Yotsumoto Y, Katsuki T, Yoda Y, Masuda T, Nomura M, Shiraki N, Inui H, Yamaji R Tags: Am J Physiol Endocrinol Metab Source Type: research

Akkermansia muciniphila abundance is lower in severe obesity but its increased level after bariatric surgery is not associated with metabolic health improvement.
cute;ment K Abstract The gut bacterial species, Akkermansia muciniphila is associated with a healthier clinical profile. The purpose of this study was to determine the association between A. muciniphila and glucose homeostasis in patients undergoing bariatric surgery (BS): gastric banding (GB) or Roux-en-Y gastric bypass (RYGB). This non-randomized prospective study included 65 women with severe obesity. Longitudinal analysis included subjects for whom A. muciniphila data was available at follow up (1, 3, and 12 months; GB (N=10) or RYGB (N=11)). Glucose homeostasis markers were measured under fasting or during an...
Source: American Journal of Physiology. Endocrinology and Metabolism - July 2, 2019 Category: Physiology Authors: Dao MC, Belda E, Prifti E, Everard A, Kayser BD, Bouillot JL, Chevallier JM, Pons N, Le Chatelier E, Ehrlich D, Doré J, Aron-Wisnewsky J, Zucker JD, Cani PD, Clément K Tags: Am J Physiol Endocrinol Metab Source Type: research

PGC-1 α regulates mitochondrial properties beyond biogenesis with aging and exercise training.
In conclusion, the present study provides evidence that PGC-1α regulates submaximal ADP-stimulated respiration, ROS emission and mitochondrial network structure in mouse skeletal muscle during aging and exercise training. PMID: 31265325 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Endocrinology and Metabolism)
Source: American Journal of Physiology. Endocrinology and Metabolism - July 2, 2019 Category: Physiology Authors: Halling JF, Jessen H, Nøhr-Meldgaard J, Thiellesen Buch B, Masselkhi Christensen N, Gudiksen A, Ringholm S, Neufer PD, Prats C, Pilegaard H Tags: Am J Physiol Endocrinol Metab Source Type: research

EPA and DHA elicit distinct transcriptional responses to high-fat feeding in skeletal muscle and liver.
Abstract Omega-3 fatty acids (n-3 PUFAs) exert numerous beneficial biological effects and attenuate diet-induced insulin resistance in rodent models. In the present study, the independent, tissue-specific effects of two nutritionally-relevant n-3 PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), were characterized in the context of a high fat diet (HFD). EPA and DHA supplementation (3.2% of total fat), in 6-month-old male, C57BL/6 mice fed HFD (60% fat) partially mitigated reductions in insulin sensitivity. At 5 weeks, the area above the curve below baseline glucose following an intraperitoneal in...
Source: American Journal of Physiology. Endocrinology and Metabolism - July 2, 2019 Category: Physiology Authors: Kunz HE, Dasari S, Lanza IR Tags: Am J Physiol Endocrinol Metab Source Type: research

A Novel Natural Tracer method to measure Complex Carbohydrate Metabolism.
We present a novel triple tracer approach to estimate postprandial turnover of complex carbohydrate containing mixed meals using the natural 13C abundance of polysaccharides contained in commercially available grains in healthy adults. PMID: 31265327 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Endocrinology and Metabolism)
Source: American Journal of Physiology. Endocrinology and Metabolism - July 2, 2019 Category: Physiology Authors: Basu R, Schiavon M, Petterson XM, Hinshaw L, Slama M, Carter R, Dalla Man C, Cobelli C, Basu A Tags: Am J Physiol Endocrinol Metab Source Type: research

Excess Membrane Cholesterol is an Early Contributing Reversible Aspect of Skeletal Muscle Insulin Resistance in C57BL/6NJ Mice Fed a Western-Style High-Fat Diet.
Abstract Skeletal muscle insulin resistance manifests shortly after high-fat feeding, yet mechanisms are not known. Here we set out to determine whether excess skeletal muscle membrane cholesterol and cytoskeletal derangement known to compromise glucose transporter GLUT4 regulation occurs early after high-fat feeding. We fed six-week old male C57BL/6NJ mice either a low-fat (LF, 10% kcal) or high-fat (HF, 45% kcal) diet for one week. This HF-feeding challenge was associated with an increase, albeit slight, in body mass, glucose intolerance and hyperinsulinemia. Liver analyses did not reveal signs of hepatic insuli...
Source: American Journal of Physiology. Endocrinology and Metabolism - June 25, 2019 Category: Physiology Authors: Grice BA, Barton KJ, Covert JD, Kreilach AM, Tackett L, Brozinick JT, Elmendorf JS Tags: Am J Physiol Endocrinol Metab Source Type: research

Obeticholic acid ameliorates dyslipidemia but not glucose tolerance in a mouse model of gestational diabetes.
n C Abstract Metabolism alters markedly with advancing gestation, characterized by progressive insulin resistance, dyslipidemia, and raised serum bile acids. The nuclear receptor FXR has an integral role in bile acid homeostasis and modulates glucose and lipid metabolism. FXR is known to be functionally suppressed in pregnancy. The FXR agonist, obeticholic acid (OCA) improves insulin sensitivity in type 2 diabetic patients with non-alcoholic fatty liver disease. We therefore hypothesized that OCA treatment during pregnancy could improve disease severity in a mouse model of gestational diabetes mellitus (GDM). C57B...
Source: American Journal of Physiology. Endocrinology and Metabolism - June 25, 2019 Category: Physiology Authors: McIlvride S, Nikolova V, Fan HM, McDonald JAK, Wahlström A, Bellafante E, Jansen E, Adorini L, Shapiro D, Jones P, Marchesi JR, Marschall HU, Williamson C Tags: Am J Physiol Endocrinol Metab Source Type: research

Activation of NPRs and UCP1-independent pathway following CB1R antagonist treatment is associated with adipose tissue beiging in fat-fed male dogs.
In this study, we probed for genes associated with beiging and explored longitudinal molecular mechanisms by which the beiging process occurs. HFD dogs received either RIM (HFD+RIM) or placebo (HFD+PL) for 16 weeks. Several genes involved in beiging were increased in HFD+RIM compared to pre-fat, HFD, and HFD+PL. We evaluated lipolysis and its regulators including natriuretic peptide (NP) and its receptors (NPRs), β-1 and β-3 adrenergic receptor (β1R, β3R) genes. These genes were increased in WAT depots, accompanied by an increase in lipolysis in HFD+RIM. In addition, RIM decreased markers of inflammatio...
Source: American Journal of Physiology. Endocrinology and Metabolism - June 25, 2019 Category: Physiology Authors: Iyer MS, Paszkiewicz RL, Bergman RN, Richey JM, Woolcott OO, Asare Bediako I, Wu Q, Kim SP, Stefanovski D, Kolka CM, Clegg DJ, Kabir M Tags: Am J Physiol Endocrinol Metab Source Type: research

Resistance Exercise-Induced Hormonal Response Promotes Satellite Cell Proliferation in Untrained Men but not in Women.
Abstract The purpose was to determine the effect of resistance exercise (RE)-induced hormonal changes on satellite cell (SC) myogenic state in response to muscle damage. Untrained men (n=10, 22±3y) and women (n=9, 21±4y) completed 2 sessions of 80 unilateral maximal eccentric knee extensions followed by either an upper body RE protocol (EX) or a 20-min rest (CON). Muscle samples were collected and analyzed for protein content of Pax7, MyoD, myogenin, cyclin D1, p21 before (PRE), 12h, and 24h after the session was completed. Serum testosterone, growth hormone, cortisol, and myoglobin concentrations we...
Source: American Journal of Physiology. Endocrinology and Metabolism - June 25, 2019 Category: Physiology Authors: Luk HY, Levitt DE, Boyett JC, Rojas S, Flader SM, McFarlin BK, Vingren JL Tags: Am J Physiol Endocrinol Metab Source Type: research

Differential effects of a 40 hour fast and bile acid supplementation on human GLP-1 and FGF19 responses.
CONCLUSIONS: Unexpectedly, 40 hours of fasting increased both GLP-1 and FGF19 where the former appeared bile acid independent and the latter bile acid dependent. Second, a single dose of gDCA increased postprandial GLP-1. Therefore, our data add complexity to the physiological regulation of the enterokines GLP-1 and FGF19 by bile acids. PMID: 31237451 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Endocrinology and Metabolism)
Source: American Journal of Physiology. Endocrinology and Metabolism - June 25, 2019 Category: Physiology Authors: Van Nierop FS, Meessen ECE, Nelissen KGM, Achterbergh R, Lammers LA, Vaz FM, Mathôt RAA, Klümpen HJ, Olde Damink SW, Schaap FG, Romijn JA, Kemper EM, Soeters MR Tags: Am J Physiol Endocrinol Metab Source Type: research

The IL-6-neutralizing sIL-6R/sgp130 buffer system is disturbed in patients with type 2 diabetes.
Abstract Serum levels of interleukin-6 (IL-6) are increased in patients with type 2 diabetes (T2D). IL-6 exerts its pleiotropic effects via the IL-6 α-receptor (IL-6R), which exists in membrane-bound and soluble forms (sIL-6R), and activates cells via the β-receptor glycoprotein 130 (gp130). The nonsynonymous single nucleotide polymorphism (SNP) rs2228145 (Asp358Ala) within the IL6R locus is associated with T2D. The aim of this study was to determine whether sIL-6R in combination with soluble gp130 (sgp130) is able to form an IL-6-neutralizing buffer in healthy subjects, and whether this is disturbed in...
Source: American Journal of Physiology. Endocrinology and Metabolism - June 25, 2019 Category: Physiology Authors: Aparicio-Siegmund S, Garbers Y, Flynn CM, Waetzig GH, Gouni-Berthold I, Krone W, Berthold HK, Laudes M, Rose-John S, Garbers C Tags: Am J Physiol Endocrinol Metab Source Type: research

Linking bioenergetic function of mitochondriato tissue-specific molecular fingerprints.
, Lehmann R Abstract Mitochondria are dynamic organelles with diverse functions in tissues such as liver and skeletal muscle. To unravel the mitochondrial contribution to tissue-specific physiology, we performed a systematic comparison of the mitochondrial proteome and lipidome of mice and assessed the consequences hereof for respiration. Liver and skeletal muscle mitochondrial protein composition was studied by data-independent UHPLC-MS/MS-proteomics, lipid profiles were compared by UHPLC-MS/MS lipidomics. Mitochondrial function was investigated by high-resolution respirometry in samples from mice and humans. Enz...
Source: American Journal of Physiology. Endocrinology and Metabolism - June 18, 2019 Category: Physiology Authors: Kappler L, Hoene M, Hu C, von Toerne C, Li J, Bleher D, Hoffmann C, Böhm A, Kollipara L, Zischka H, Königsrainer A, Häring HU, Peter A, Xu G, Sickmann A, Hauck SM, Weigert C, Lehmann R Tags: Am J Physiol Endocrinol Metab Source Type: research

A Comparative Study of Mitochondrial Respiration in Circulating Blood Cells and Skeletal Muscle Fibers in Women.
eim E Abstract Skeletal muscle mitochondrial respiration is thought to be altered in obesity, insulin resistance and type 2 diabetes; however, the invasive nature of tissue biopsies is an important limiting factor for studying mitochondrial function. Recent findings suggest that bioenergetics profiling of circulating cells may inform on mitochondrial function in other tissues in lieu of biopsies. Thus, we sought to determine whether mitochondrial respiration in circulating cells (peripheral blood mononuclear cells [PBMCs] and platelets) reflects that of skeletal muscle fibers derived from the same subjects. PBMCs,...
Source: American Journal of Physiology. Endocrinology and Metabolism - June 18, 2019 Category: Physiology Authors: Rose S, Carvalho E, Diaz EC, Cotter M, Bennuri SC, Azhar G, Frye RE, Adams SH, Børsheim E Tags: Am J Physiol Endocrinol Metab Source Type: research

Alterations of skeletal muscle bioenergetics in a mouse with F508del mutation leading to a cystic fibrosis-like condition.
Abstract High energy expenditure is reported in cystic fibrosis (CF) animal models and patients. Alterations in skeletal muscle oxidative capacity, fuel utilization, and creatine kinase-phosphocreatine system suggest mitochondrial dysfunction. Studies were performed on congenic C57BL/6J and F508del (Cftrtm1kth) mice. Indirect calorimetry was used to measure gas exchange to evaluate aerobic capacity during treadmill exercise. The bioenergetic function of skeletal muscle subsarcolemmal (SSM) and interfibrillar (IFM) mitochondria was evaluated using an integrated approach combining measurement of the rate of oxidativ...
Source: American Journal of Physiology. Endocrinology and Metabolism - June 18, 2019 Category: Physiology Authors: Lai N, Kummitha C, Drumm M, Hoppel C Tags: Am J Physiol Endocrinol Metab Source Type: research

The pregnane X receptor and its microbiota-derived ligand, indole 3-propionic acid, regulate endothelium-dependent vasodilation.
Abstract We proposed that circulating metabolites generated by the intestinal microbiota can affect vascular function. One such metabolite, indole 3-propionic acid(IPA), can activate the pregnane X receptor(PXR), a xenobiotic-activated nuclear receptor present in many tissues, including the vascular endothelium. We hypothesized that IPA could regulate vascular function by modulating PXR activity. To test this, Pxr+/+mice were administered a broad-spectrum antibiotics for two weeks, with IPA supplementation. Vascular function was evaluated by bioassay using aorta and pulmonary artery-ring tissue from antibiotic-tre...
Source: American Journal of Physiology. Endocrinology and Metabolism - June 18, 2019 Category: Physiology Authors: Pulakazhi Venu VK, Saifeddine M, Mihara K, Tsai YC, Nieves K, Alston L, Mani S, McCoy KD, Hollenberg MD, Hirota SA Tags: Am J Physiol Endocrinol Metab Source Type: research

Pyridostigmine regulates glucose metabolism and mitochondrial homeostasis to reduce myocardial vulnerability to injury in diabetic mice.
This study may provide a potential therapeutic target for myocardial damage in diabetic patients. PMID: 31211620 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Endocrinology and Metabolism)
Source: American Journal of Physiology. Endocrinology and Metabolism - June 18, 2019 Category: Physiology Authors: Yang Y, Zhao M, Yu XJ, Liu LZ, He X, Deng J, Zang WJ Tags: Am J Physiol Endocrinol Metab Source Type: research

Mouse Trefoil Factor 3 (Tff3) Ameliorated hepatic steatosis via increasing Peroxisome Proliferator-activated Receptor- α (PPARα) mediated fatty acid oxidation.
Mouse Trefoil Factor 3 (Tff3) Ameliorated hepatic steatosis via increasing Peroxisome Proliferator-activated Receptor-α (PPARα) mediated fatty acid oxidation. Am J Physiol Endocrinol Metab. 2019 Jun 18;: Authors: Wu X, Zheng H, Yang R, Luan X, Zhang L, Jin Y, Jin Q, Xue J Abstract Hepatic trefoil factor 3 (Tff3) was identified as a potential protein for the treatment of diabetes, yet the effect of Tff3 on non-alcoholic fatty liver disease (NAFLD) has never been explored. Here, we found that the expression of hepatic Tff3 was significantly decreased in NAFLD mice models, suggesting that Tff...
Source: American Journal of Physiology. Endocrinology and Metabolism - June 18, 2019 Category: Physiology Authors: Wu X, Zheng H, Yang R, Luan X, Zhang L, Jin Y, Jin Q, Xue J Tags: Am J Physiol Endocrinol Metab Source Type: research

Exogenous H2S reduces acetylation levels of mitochondrial respiratory enzymes via regulating NAD+-SIRT3 pathway in cardiac tissues of db/db mice.
CONCLUSION: We conclude that exogenous H2S plays a critical role in improving cardiac mitochondrial function in diabetes by upregulating SIRT3. PMID: 31184932 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Endocrinology and Metabolism)
Source: American Journal of Physiology. Endocrinology and Metabolism - June 11, 2019 Category: Physiology Authors: Sun Y, Teng Z, Sun X, Zhang L, Chen J, Wang B, Lu F, Liu N, Yu M, Peng S, Wang Y, Zhao D, Zhao Y, Ren H, Cheng Z, Dong S, Lu F, Zhang W Tags: Am J Physiol Endocrinol Metab Source Type: research

Ghrelin in rat pancreatic islets decreases islet blood flow.
on PO Abstract The peptide ghrelin is mainly produced in some of the epithelial cells in the stomach, but also, during starvation, by the ε-cells in the endocrine pancreas. Ghrelin, as an endogenous ligand for the growth hormone secretagogue receptor (GHS-R1α), exerts a variety of metabolic functions including stimulation of appetite and weight gain. Its complete role is not yet fully understood, including whether it has any vascular functions. The present study evaluated if ghrelin affects pancreatic and islet blood flow. Ghrelin and the GHS-R1α receptor antagonist GHRP-6 were injected intrave...
Source: American Journal of Physiology. Endocrinology and Metabolism - May 7, 2019 Category: Physiology Authors: Drott CJ, Franzén P, Carlsson PO Tags: Am J Physiol Endocrinol Metab Source Type: research

Hydrogen Sulfide Inhibits Ca2+-induced Mitochondrial Permeability Transition Pore (MPTP) Opening in Type-1 Diabetes.
Abstract Hydrogen sulfide (H2S) attenuates N-Methyl-D-Aspartate receptor-R1 (NMDA-R1) and mitigates diabetic renal damage; however, the molecular mechanism is not well known. While NMDA-R1 facilitates Ca2+ permeability, H2S is known to inhibit L-type Ca2+ channel. High Ca2+ activates cyclophilin D (CypD), a gatekeeper protein of mitochondrial permeability transition pore (MPTP), thus facilitating molecular exchange between matrix and cytoplasm causing oxidative outburst and cell death. We tested the hypothesis whether NMDA-R1 mediates Ca2+ influx causing CypD activation and MPTP opening leading to oxidative stress...
Source: American Journal of Physiology. Endocrinology and Metabolism - April 30, 2019 Category: Physiology Authors: Papu John AS, Kundu S, Pushpakumar S, Amin M, Tyagi SC, Sen U Tags: Am J Physiol Endocrinol Metab Source Type: research

Chip-based sensing of membrane release of unprocessed cell surface proteins in vitro and in serum and its (patho)physiological relevance.
ml;p MH Abstract To study the possibility that components of eukaryotic plasma membranes are released under certain (patho)physiological conditions, a chip-based sensor was developed for detection of cell surface proteins, which are anchored at the outer leaflet of eukaryotic plasma membranes by a covalently attached glycolipid, exclusively, and might be prone to spontaneous or regulated release on basis of their amphiphilic character. For this, unprocessed full-length glycosylphosphatidylinositol-anchored proteins (GPI-AP) with associated phospholipids were specifically captured and detected by a chip- and microf...
Source: American Journal of Physiology. Endocrinology and Metabolism - April 30, 2019 Category: Physiology Authors: Müller GA, Herling AW, Stemmer K, Lechner A, Tschöp MH Tags: Am J Physiol Endocrinol Metab Source Type: research

Sex modulates hepatic mitochondrial adaptations to high fat diet and physical activity.
In conclusion, hepatic mitochondrial adaptations to HFD and treatment of HFD-induced steatosis with VWR are more dependent on sex than PGC-1a or BNIP3. PMID: 31039007 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Endocrinology and Metabolism)
Source: American Journal of Physiology. Endocrinology and Metabolism - April 30, 2019 Category: Physiology Authors: McCoin CS, Von Schulze A, Allen J, Fuller KN, Xia Q, Koestler DC, Houchen CJ, Maurer A, Dorn Ii GW, Shankar K, Morris EM, Thyfault JP Tags: Am J Physiol Endocrinol Metab Source Type: research

Loss of ACOT7 potentiates seizures and metabolic dysfunction.
Abstract Neurons uniquely antagonize fatty acid utilization by hydrolyzing the activated form of fatty acids, long chain acyl-CoAs, via the enzyme acyl-CoA thioesterase 7, Acot7. The loss of Acot7 results in increased fatty acid utilization in neurons and exaggerated stimulus-evoked behavior. To understand the contribution of Acot7 to seizure susceptibility we generated Acot7 KO mice and assayed their response to kainate-induced seizures. Acot7 KO mice exhibited potentiated behavioral and molecular indices of seizure severity following kainic acid administration suggesting that fatty acid metabolism in neurons can...
Source: American Journal of Physiology. Endocrinology and Metabolism - April 30, 2019 Category: Physiology Authors: Bowman CE, Selen Alpergin ES, Ellis JM, Wolfgang MJ Tags: Am J Physiol Endocrinol Metab Source Type: research

Hepatic MyD88 regulates liver Inflammation by altering the synthesis of oxysterols.
This study aims to investigate the function of hepatic MyD88, a central adaptor of innate immunity, on metabolism. Although its role in inflammation is well known, we have recently discovered that MyD88 can also mediate energy, lipid and glucose metabolism.More precisely, we have reported that mice harboring hepatocyte-specific deletion of MyD88 (Myd88ΔHep) were predisposed to glucose intolerance, liver fat accumulation and inflammation. However, the molecular events explaining the onset of hepatic disorders and inflammation remain to be elucidated. To investigate the molecular mechanism, Myd88ΔHepand WT mice w...
Source: American Journal of Physiology. Endocrinology and Metabolism - April 30, 2019 Category: Physiology Authors: Lefort C, Van Hul M, Delzenne NM, Everard A, Cani PD Tags: Am J Physiol Endocrinol Metab Source Type: research

Gut bacteria are critical for optimal muscle function:a potential link with glucose homeostasis.
Ramonatxo C Abstract Gut microbiota is involved in the development of several chronic diseases, including diabetes, obesity and cancer, through its interactions with the host organs. It has been suggested that the cross-talk between gut microbiota and skeletal muscle plays a role in different pathological conditions, such as intestinal chronic inflammation and cachexia. However, it remains unclear whether gut microbiota directly influences skeletal muscle function. In this work, we studied the impact of gut microbiota modulation on mice skeletal muscle function and investigated the underlying mechanisms. We determ...
Source: American Journal of Physiology. Endocrinology and Metabolism - April 30, 2019 Category: Physiology Authors: Nay K, Jollet M, Goustard B, Baati N, Vernus B, Pontones M, Lefeuvre-Orfila L, Bendavid C, Rué O, Mariadassou M, Bonnieu A, Ollendorff V, Lepage P, Derbré F, Koechlin-Ramonatxo C Tags: Am J Physiol Endocrinol Metab Source Type: research

Subcutaneous Adipose Tissue Free Fatty Acid Uptake Measured Using Positron Emission Tomography and Adipose Biopsies in Humans.
Abstract PET radiopharmaceuticals can noninvasively measure free fatty acid (FFA) uptake into adipose tissue. We studied 29 volunteers to test whether abdominal and femoral subcutaneous adipose tissue FFA uptake measured using [1-11C]palmitate PET agrees with FFA storage rates measured using an intravenous bolus of [1-14C]palmitate and adipose biopsies. The dynamic left ventricular cavity PET images combined with blood sample radioactivity corrected for the 11CO2 content were used to create the blood time activity curve (TAC) and the constant (Ki) was determined using Patlak analysis of the TACs generated for regi...
Source: American Journal of Physiology. Endocrinology and Metabolism - April 23, 2019 Category: Physiology Authors: Cao Y, Gathaiya N, Han Q, Kemp BJ, Jensen MD Tags: Am J Physiol Endocrinol Metab Source Type: research

The autonomic nervous system regulates pancreatic beta-cell proliferation in adult male rats.
out V Abstract The pancreatic beta-cell responds to changes in the nutrient environment to maintain glucose homeostasis by adapting its function and mass. Nutrients can act directly on the beta-cell and also indirectly through the brain via autonomic nerves innervating islets. Despite the importance of the brain-islet axis in insulin secretion, relatively little is known regarding its involvement in beta-cell proliferation. We previously demonstrated that prolonged infusions of nutrients in rats provoke a dramatic increase in beta-cell proliferation in part due to the direct action of nutrients. Here, we addressed...
Source: American Journal of Physiology. Endocrinology and Metabolism - April 23, 2019 Category: Physiology Authors: Moullé VS, Tremblay C, Castell AL, Vivot K, Ethier M, Fergusson G, Alquier T, Ghislain J, Poitout V Tags: Am J Physiol Endocrinol Metab Source Type: research

Repetitive hypoglycaemia reduces the activation of glucose responsive neurons in the C1 and C3 medullary brain regions to subsequent hypoglycaemia.
Abstract The impaired ability of the autonomic nervous system to respond to hypoglycaemia is termed 'hypoglycaemia-associated autonomic failure' (HAAF). This life-threatening phenomenon results from at least two recent episodes of hypoglycaemia, but the pathology underpinning HAAF remains largely unknown. Although naloxone appears to improve hypoglycaemia counter-regulation under controlled conditions, hypoglycaemia prevention remains the current mainstay therapy for HAAF. Adrenaline-synthesising neurons in the rostroventrolateral (C1) and dorsomedial (C3) medulla project to the subset of sympathetic preganglionic...
Source: American Journal of Physiology. Endocrinology and Metabolism - April 23, 2019 Category: Physiology Authors: Kakall ZM, Kavurma MM, Cohen EM, R Howe P, Nedoboy PE, Pilowsky PM Tags: Am J Physiol Endocrinol Metab Source Type: research

Medium-chain triglyceride diet stimulates less GIP secretion and suppresses body weight and fat mass gain compared with long-chain triglyceride diet.
In this study, we evaluated the effect of single MCT oil administration on GIP secretion, and compared the effect of long-term MCT and LCT diet on body weight and fat mass gain in wild-type (WT) and GIP-knockout (GIP KO) mice. Single administration of LCT oil induced GIP secretion but that of MCT oil did not in WT mice. Long-term intake of LCT diet induced GIP hypersecretion and significant body weight and fat mass gain compared to that of control fat (CF) diet in WT mice. In contrast, MCT diet did not induce GIP hypersecretion, and MCT diet-fed mice showed smaller increase in body weight and fat mass gain compared to CF d...
Source: American Journal of Physiology. Endocrinology and Metabolism - April 16, 2019 Category: Physiology Authors: Murata Y, Harada N, Yamane S, Iwasaki K, Ikeguchi E, Kanemaru Y, Harada T, Sankoda A, Shimazu-Kuwahara S, Joo E, Poudyal H, Inagaki N Tags: Am J Physiol Endocrinol Metab Source Type: research

Sex-specific regulation of stress-induced fetal glucocorticoid surge by the mouse placenta.
Abstract Antenatal stress increases the prevalence of diseases in later life, which shows a strong sex-specific effect. However, the underlying mechanisms remain unknown. Maternal glucocorticoids can be elevated by stress and are potential candidates to mediate the effects of stress on the offspring sex-specifically. A comprehensive evaluation of dynamic maternal and placental mechanisms modulating fetal glucocorticoid exposure upon maternal stress was long overdue. Here, we addressed this gap in knowledge by investigating sex-specific responses to mid-gestational stress in mice. We observed increased levels of ma...
Source: American Journal of Physiology. Endocrinology and Metabolism - April 16, 2019 Category: Physiology Authors: Wieczorek A, Perani CV, Nixon M, Constancia M, Sandovici I, Zazara DE, Leone G, Zhang MZ, Arck PC, Solano ME Tags: Am J Physiol Endocrinol Metab Source Type: research

Sustained hypoxemia in late gestation potentiates hepatic gluconeogenic gene expression but does not activate glucose production in the ovine fetus.
Abstract Fetal hypoxemia is associated with pregnancy conditions that cause an early activation of fetal glucose production. However, the independent role of hypoxemia to activate this pathway is not well understood. We hypothesized that fetal hypoxemia would activate fetal glucose production by decreasing umbilical glucose uptake and increasing counter-regulatory hormone concentrations. We induced hypoxemia for 9 days with maternal tracheal N2 gas insufflation to reduce maternal and fetal arterial pO2 by ~20% (HOX) compared with fetuses from ewes receiving intratracheal compressed air (CON). At 0.9 of gestation, ...
Source: American Journal of Physiology. Endocrinology and Metabolism - April 9, 2019 Category: Physiology Authors: Jones AK, Rozance PJ, Brown LD, Goldstrohm DA, Hay WW, Limesand SW, Wesolowski SR Tags: Am J Physiol Endocrinol Metab Source Type: research

Liver X Receptor α Activation Enhances Cholesterol Secretion in Lactating Mammary Epithelium.
Liver X Receptor α Activation Enhances Cholesterol Secretion in Lactating Mammary Epithelium. Am J Physiol Endocrinol Metab. 2019 Apr 09;: Authors: Grinman DY, Careaga VP, Wellberg EA, Dansey MV, Kordon EC, Anderson SM, Maier MS, Burton G, MacLean PS, Rudolph MC, Pecci A Abstract Liver-X-Receptors are ligand-dependent transcription factors activated by cholesterol metabolites. These receptors induce a suite of target genes required for de novo synthesis of triglycerides and cholesterol transport in many tissues. Two different isoforms -LXRα and LXRβ- have been well characterized in li...
Source: American Journal of Physiology. Endocrinology and Metabolism - April 9, 2019 Category: Physiology Authors: Grinman DY, Careaga VP, Wellberg EA, Dansey MV, Kordon EC, Anderson SM, Maier MS, Burton G, MacLean PS, Rudolph MC, Pecci A Tags: Am J Physiol Endocrinol Metab Source Type: research

Aging impairs mouse skeletal muscle macrophage polarization and muscle-specific abundance during recovery from disuse.
Abstract Impaired recovery of aged muscle following a disuse event is unresolved issue facing the older adult population. Although investigations in young animals has suggested that rapid regrowth of skeletal muscle following a disuse event involves a coordinated involvement of skeletal muscle macrophages, this phenomenon has not yet been thoroughly tested as an explaination for impaired muscle recovery in aging. To examine this hypothesis, young (3 month) and old (24-26 month) malemice were examined as controls, following 2 weeks of hindlimb unloading (HU) and following 4 (RL4)and 7 (RL7)days of reloading after H...
Source: American Journal of Physiology. Endocrinology and Metabolism - April 9, 2019 Category: Physiology Authors: Reidy PT, McKenzie AI, Mahmassani ZS, Petrocelli JJ, Nelson DB, Lindsay CC, Gardner JE, Morrow VR, Keefe AC, Huffaker TB, Stoddard GJ, Kardon G, O'Connell RM, Drummond MJ Tags: Am J Physiol Endocrinol Metab Source Type: research

Role of exercise-induced hepatokines in metabolic disorders.
Abstract The health-promoting effects of physical activity to prevent and treat metabolic disorders are numerous. However, the underlying molecular mechanisms are not yet completely deciphered. In recent years, studies have reported that the liver can be considered as a secretory organ by releasing specific proteins called hepatokines. Some of these hepatokines are involved in the whole-body metabolic homeostasis and participates in the development of metabolic diseases. In this regards, the present review describes the role of FGF21, Fetuin-A, Angiopoietin-like protein 4 and Follistatin in metabolic diseases and ...
Source: American Journal of Physiology. Endocrinology and Metabolism - April 9, 2019 Category: Physiology Authors: Ennequin G, Sirvent P, Whitham M Tags: Am J Physiol Endocrinol Metab Source Type: research

Modest changes to glycemic regulation are sufficient to maintain glucose flux in healthy humans following overfeeding with a habitual macronutrient composition.
Abstract Currently, it is unclear whether short-term overfeeding in healthy people significantly affects postprandial glucose regulation, as most human overfeeding studies have utilized induced experimental conditions such as the euglycemic-hyperinsulinemic clamp technique to assess glucoregulation. The aim of this study was to quantify glucose fluxes (rates of meal glucose appearance (Ra), disposal (Rd) and endogenous glucose production (EGP)) in response to 5 and 28 days of overfeeding (+45% energy) while maintaining the habitual diet's macronutrient composition (31.0 ± 1.9 % fat; 48.6 ± 2.2 % carb...
Source: American Journal of Physiology. Endocrinology and Metabolism - April 9, 2019 Category: Physiology Authors: Morrison DJ, Kowalski GM, Bruce CR, Wadley GD Tags: Am J Physiol Endocrinol Metab Source Type: research

Lipolysis Defect in White Adipose Tissue and Rapid Weight Regain.
Abstract Weight regain after weight loss is a well described-phenomena in both humans and animal models of obesity. Reduced energy expenditure and increased caloric intake are considered the main drivers of weight regain. We hypothesized that adipose tissue with obesity memory (OM), has a tissue-autonomous lipolytic defect allowing increased efficiency of lipid storage. We utilized a mouse model of diet induced obesity, which was subjected to 60% caloric restriction to achieve lean body weight, followed by a short period of high fat diet (HFD) re-challenge. Age-matched lean mice fed HFD for the first time were use...
Source: American Journal of Physiology. Endocrinology and Metabolism - April 9, 2019 Category: Physiology Authors: Kasher-Meron M, Youn DY, Zong H, Pessin JE Tags: Am J Physiol Endocrinol Metab Source Type: research

Effect of PPAR-gamma agonist on aerobic exercise capacity in relation to body fat distribution in men with type 2 diabetes and coronary artery disease.
CONCLUSIONS: Treatment with the insulin sensitizer PPAR-gamma agonist rosiglitazone in patients with T2DM and CAD is associated with a worsening in exercise capacity, which seems to be mainly attributable to weight gain and subcutaneous fat mass expansion. PMID: 30964707 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Endocrinology and Metabolism)
Source: American Journal of Physiology. Endocrinology and Metabolism - April 9, 2019 Category: Physiology Authors: Bastien M, Poirier P, Brassard P, Arsenault BJ, Bertrand OF, Després JP, Costerousse O, Piche ME Tags: Am J Physiol Endocrinol Metab Source Type: research

C/EBP β mediates palmitate-induced musclin expression via the regulation of PERK/ATF4 pathways in myotubes.
C/EBPβ mediates palmitate-induced musclin expression via the regulation of PERK/ATF4 pathways in myotubes. Am J Physiol Endocrinol Metab. 2019 Apr 09;: Authors: Guo Q, Hu H, Liu X, Yang D, Yin Y, Zhang B, He H, Oh Y, Wu Q, Liu C, Gu N Abstract Musclin is a muscle-secreted cytokine that disrupts glucose uptake and glycogen synthesis in type 2 diabetes. The purpose of this study was to investigate the mechanisms responsible for the regulation of musclin gene expression in response to treatment with palmitate. RNA sequencing results showed that biological processes activated by palmitate are mainly ...
Source: American Journal of Physiology. Endocrinology and Metabolism - April 9, 2019 Category: Physiology Authors: Guo Q, Hu H, Liu X, Yang D, Yin Y, Zhang B, He H, Oh Y, Wu Q, Liu C, Gu N Tags: Am J Physiol Endocrinol Metab Source Type: research

Kr üppel-like factor 4 plays a role in the luteal transition in steroidogenesis by down-regulating Cyp19A1 expression.
Krüppel-like factor 4 plays a role in the luteal transition in steroidogenesis by down-regulating Cyp19A1 expression. Am J Physiol Endocrinol Metab. 2019 Apr 02;: Authors: Choi H, Ryu KY, Roh J Abstract The transition from granulosa cell to luteal cell involves a change from estrogen production to predominantly progesterone production. We analyzed the role of Krüppel-like factor 4 (Klf4), a transcriptional repressor used to generate pluripotent cells, in that transition. After luteinizing hormone/human chorionic gonadotropin (LH/hCG) treatment of preovulatory follicles, a major but transient...
Source: American Journal of Physiology. Endocrinology and Metabolism - April 2, 2019 Category: Physiology Authors: Choi H, Ryu KY, Roh J Tags: Am J Physiol Endocrinol Metab Source Type: research

Quantifying the contribution of dietary protein to whole body protein kinetics: examination of the intrinsically-labeled proteins method.
Abstract Intrinsically-labeled dietary proteins have been used to trace various aspects of digestion and absorption, including quantifying the contribution of dietary protein to observed post-prandial amino acid and protein kinetics in human subjects. Quantification of the rate of appearance in peripheral blood of an unlabeled (tracee) amino acid originating from an intrinsically-labeled protein (exogenous Ra) requires the assumption that there is no dilution of the isotope enrichment of the protein-bound amino acid in the gastrointestinal tract (GIT) or across the splanchnic bed. It must also be assumed that the ...
Source: American Journal of Physiology. Endocrinology and Metabolism - April 2, 2019 Category: Physiology Authors: Wolfe RR, Park S, Kim IY, Starck C, Marquis BJ, Ferrando AA, Moughan PJ Tags: Am J Physiol Endocrinol Metab Source Type: research

Loss of the glucocorticoid receptor in zebrafish improves muscle glucose availability and increases growth.
Abstract Chronic stress and the associated elevation in corticosteroid levels increase muscle protein catabolism. We hypothesized that the GR-regulated restriction of muscle glucose availability may play a role in the increased protein catabolism during chronic stress. To test this, we generated a ubiquitous GR knockout (GRKO) zebrafish to determine the physiological consequence of glucocorticoid stimulation on muscle metabolism and growth. Adult GRKO zebrafish had higher body mass, and this corresponded with an increased protein and lipid, but not carbohydrate content. GRKO fish were hypercortisolemic, but they e...
Source: American Journal of Physiology. Endocrinology and Metabolism - April 2, 2019 Category: Physiology Authors: Faught E, Vijayan MM Tags: Am J Physiol Endocrinol Metab Source Type: research

Chronic fructose renders pancreatic beta-cells hyper-responsive to glucose-stimulated insulin secretion through extracellular ATP signaling.
Abstract Fructose is widely used as a sweetener in processed food and since then is associated with metabolic disorders, such as obesity. However, the underlying cellular mechanisms remain unclear, in particular regarding the pancreatic beta-cell. Here, we investigated the effects of chronic exposure to fructose on the function of insulinoma cells and isolated mouse and human pancreatic islets. Although fructose per se did not acutely stimulate insulin exocytosis, our data show that chronic fructose rendered rodent and human beta-cells hyper-responsive to intermediate physiological glucose concentrations. Fructose...
Source: American Journal of Physiology. Endocrinology and Metabolism - March 26, 2019 Category: Physiology Authors: Bartley C, Brun T, Oberhauser L, Grimaldi M, Molica F, Kwak BR, Bosco D, Chanson M, Maechler P Tags: Am J Physiol Endocrinol Metab Source Type: research

Spatial and temporal studies of metabolic activity: Contrasting biochemical kinetics in tissues and pathways during fasted and fed states.
Abstract The regulation of nutrient homeostasis, i.e. the ability to transition between fasted and fed states, is fundamental in maintaining health. Since food is typically consumed over limited (anabolic) periods, dietary components must be processed and stored to counterbalance the catabolic stress that occurs between meals. Herein, we contrast tissue- and pathway-specific metabolic activity in fasted and fed states. We demonstrate that knowledge of biochemical kinetics which is obtained from opposite ends of the energetic spectrum can allow mechanism-based differentiation of healthy and disease phenotypes. Rat ...
Source: American Journal of Physiology. Endocrinology and Metabolism - March 26, 2019 Category: Physiology Authors: Daurio NA, Wang Y, Chen Y, Zhou H, Carballo-Jane E, Mane J, Rodriguez CG, Zafian P, Houghton A, Addona G, McLaren DG, Zhang R, Shyong BJ, Bateman KP, Downes DP, Webb M, Kelley DE, Previs SF Tags: Am J Physiol Endocrinol Metab Source Type: research

Compensation for cold-induced thermogenesis during weight loss maintenance and regain.
Abstract Prevalence of obesity is exacerbated by low rates of successful long-term weight loss maintenance (WLM). In part, relapse from WLM to obesity is due to a reduction in energy expenditure (EE) that persists throughout WLM and relapse. Thus, interventions that increase EE might facilitate WLM. In obese mice that were calorically restricted to reduce body weight by ~20%, we manipulated EE throughout WLM and early relapse using intermittent cold exposure (ICE; 4°C, 90 min/day, 5 days/wk, within the last 3 hours of the light cycle). EE, energy intake, and spontaneous physical activity were measured during t...
Source: American Journal of Physiology. Endocrinology and Metabolism - March 26, 2019 Category: Physiology Authors: Presby DM, Jackman MR, Rudolph MC, Sherk VD, Foright RM, Houck JA, Johnson GC, Orlicky DJ, Melanson EL, Higgins JA, MacLean PS Tags: Am J Physiol Endocrinol Metab Source Type: research