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American Journal of Physiology. Endocrinology and Metabolism

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https://www.readbyqxmd.com/read/28096081/mice-with-hyperbilirubinemia-due-to-gilbert-s-syndrome-polymorphism-are-resistant-to-hepatic-steatosis-by-decreased-serine-73-phosphorylation-of-ppar%C3%AE
#1
Terry D Hinds, Peter A Hosick, Michael W Hankins, Andrea Nestor-Kalinoski, David E Stec
Gilbert's syndrome is derived from a polymorphism (TA repeat) in the hepatic UGT1A1 gene which results in decreased conjugation and increased levels of unconjugated bilirubin. Recently, we have shown that bilirubin binds directly to the fat burning nuclear peroxisome proliferator-activated receptor α (PPARα). Additionally, we have shown that serine 73 phosphorylation (Ser(P)(73)) of PPARα decreases activity by reducing its protein levels and transcriptional activity. The aim of this study was to determine if humanized mice with the Gilbert's polymorphism (HuUGT*28) have increased PPARα activation and reduced hepatic fat accumulation...
January 17, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28073780/chronic-kidney-disease-and-obesity-bias-surrogate-estimates-of-insulin-sensitivity-compared-to-the-hyperinsulinemic-euglycemic-clamp
#2
Iram Ahmad, Leila R Zelnick, Nicole R Robinson, Adriana M Hung, Bryan Kestenbaum, Kristina M Utzschneider, Steven E Kahn, Ian H de Boer
INTRODUCTION: Insulin sensitivity can be measured by procedures such as the hyperinsulinemic-euglycemic clamp or using surrogate indices. Chronic kidney disease (CKD) and obesity may differentially affect these measurements because of changes in insulin kinetics and organ-specific effects on insulin sensitivity. METHODS: In a cross-sectional study of 59 subjects with non-diabetic CKD (estimated glomerular filtration rate (GFR) <60 mL/min/1.73 m(2)) and 39 matched healthy controls, we quantified insulin sensitivity by clamp (SIclamp), oral glucose tolerance test, and fasting glucose and insulin...
January 10, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28073779/glucose-dependent-insulinotropic-polypeptide-promotes-lipid-deposition-in-subcutaneous-adipocytes-in-obese-type-2-diabetes-patients-a-maladaptive-response
#3
Sravan K Thondam, Christina Daousi, John P H Wilding, Jens J Holst, Gulizar I Ameen, Chenjing Yang, Catherine Whitmore, Silvia Mora, Daniel J Cuthbertson
: Glucose-dependent insulinotropic polypeptide (GIP) beyond its insulinotropic effects may regulate post-prandial lipid metabolism. While the insulinotropic action of GIP is known to be impaired in type 2 diabetes mellitus (T2DM), its adipogenic effect is unknown. We hypothesised GIP is anabolic in human subcutaneous adipose tissue (SAT) promoting triacylglycerol (TAG) deposition through re-esterification of non-esterified fatty acids (NEFA) and this effect may differ according to obesity status or glucose tolerance...
January 10, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28073778/overexpression-of-pgc-1%C3%AE-increases-peroxisomal-and-mitochondrial-fatty-acid-oxidation-in-human-primary-myotubes
#4
Tai-Yu Huang, Donghai Zheng, Joseph A Houmard, Jeffrey J Brault, Robert C Hickner, Ronald N Cortright
Peroxisomes are indispensable organelles for lipid metabolism in humans and their biogenesis has been assumed to be under regulation by peroxisome proliferator-activated receptors (PPARs). However, recent studies in hepatocytes suggest that the mitochondrial proliferator PGC-1α (peroxisome proliferator-activated receptor gamma coactivator-1 alpha) also acts as an upstream transcriptional regulator for enhancing peroxisomal abundance and associated activity. It is unknown whether the regulatory mechanism(s) for enhancing peroxisomal function is through the same node as mitochondrial biogenesis in human skeletal muscle (HSkM) and whether fatty acid oxidation (FAO) is affected...
January 10, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28049625/regulation-of-the-macrophage-oxytocin-receptor-in-response-to-inflammation
#5
Angela Szeto, Ni Sun-Suslow, Armando J Mendez, Rosa I Hernandez, Klaus V Wagner, Philip M McCabe
It has been demonstrated that the neuropeptide oxytocin (OT) attenuates oxidative stress and inflammation in macrophages. In the current study, we examined the role of inflammation on the expression of the oxytocin receptor (OXTR). We hypothesized that OXTR expression is increased during the inflammation though a nuclear factor kappa B (NF-κB) mediated pathway, thus responding as an acute phase protein. Inflammation was induced by treating macrophages (human primary, THP-1, and murine) with lipopolysaccharide (LPS) and monitored by expression of IL-6...
January 3, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28028037/muscle-interleukin-6-and-fasting-induced-pdh-regulation-in-mouse-skeletal-muscle
#6
Anders Gudiksen, Lærke Bertholdt, Mikkel Birkkjær Vingborg, Henriette Watson Hansen, Stine Ringholm Ringholm, Henriette Pilegaard
Fasting prompts a metabolic shift in substrate utilization from carbohydrate to predominant fat oxidation in skeletal muscle and pyruvate dehydrogenase (PDH) is seen as a controlling link between the competitive oxidation of carbohydrate and fat during metabolic challenges like fasting. Interleukin (IL)-6 has been proposed to be released from muscle with concomitant effects on both glucose and fat utilization. The aim was to test the hypothesis that IL-6 has a regulatory impact on fasting-induced suppression of skeletal muscle PDH...
December 27, 2016: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28028036/reduced-islet-function-contributes-to-impaired-glucose-homeostasis-in-fructose-fed-mice
#7
Zeenat A Asghar, Andrew Cusumano, Zihan Yan, Maria S Remedi, Kelle H Moley
Increased sugar consumption, particularly fructose, in the form of sweetened beverages and sweeteners in our diet adversely affects metabolic health. Because these effects are associated with features of the metabolic syndrome in humans, the direct effect of fructose on pancreatic islet function is unknown. We therefore examined the islet phenotype of mice fed excess fructose. Fructose-fed mice exhibited fasting hyperglycemia and glucose intolerance, but not hyperinsulinemia, dyslipidemia, or hyperuricemia...
December 27, 2016: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28028035/cardiometabolic-risk-improvement-in-response-to-a-3-yr-lifestyle-modification-program-in-men-contribution-of-improved-cardiorespiratory-fitness-vs-weight-loss
#8
Anne-Laure Borel, Julie-Anne Nazare, Aurélie Baillot, Natalie Alméras, Angelo Tremblay, Jean Bergeron, Dr Paul Poirier, Jean-Pierre Despres
OBJECTIVE: To examine the respective contributions of changes in visceral adiposity, subcutaneous adiposity, liver fat, and cardiorespiratory fitness (CRF) to the improvements in cardiometabolic risk markers observed in response to a 3-year healthy eating/physical activity lifestyle intervention. RESEARCH DESIGN AND METHODS: Ninety-four out of 144 viscerally obese but otherwise healthy men completed a 3-year lifestyle intervention. Body weight, body composition and fat distribution were assessed by anthropometry and DEXA/computed tomography...
December 27, 2016: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27998960/acute-and-chronic-hyperglycemic-effects-of-vasopressin-in-normal-rats-involvement-of-v1a-receptors
#9
Christopher Taveau, Catherine Chollet, Daniel G Bichet, Gilberto Velho, Gilles Guillon, Maithe Corbani, Ronan Roussel, Lise Bankir, Olle Melander, Nadine Bouby
Recent epidemiological studies have revealed novel relationships between low water intake or high vasopressin (AVP) and the risk of hyperglycemia and diabetes. AVP V1A and V1B receptors (R) are expressed in liver and pancreatic islets, respectively. The present study was designed to determine the impact of different levels of circulating AVP on glucose homeostasis in normal Sprague Dawley rats, and the respective roles of V1AR and V1BR. We showed that acute injection of AVP induces a dose-dependent increase in glycemia...
December 20, 2016: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27998959/exogenous-h2s-regulates-endoplasmic-reticulum-mitochondria-cross-talk-to-inhibit-apoptotic-pathways-in-stz-induced-type-i-diabetes
#10
Fan Yang, Xiangjing Yu, Ting Li, Jianjun Wu, YaJun Zhao, Aili Sun, Shiyun Dong, Jichao Wu, Xin Zhong, Changqing Xu, Fanghao Lu, Weihua Zhang
BACKGROUND: The upregulation of reactive oxygen species (ROS) is a primary cause of cardiomyocyte apoptosis in Diabetes cardiomyopathy (DCM). Mitofusin-2 (Mfn-2) is a key protein that bridges the mitochondria and endoplasmic reticulum(ER). Hydrogen sulfide (H2S)-mediated cardioprotection is related to antioxidant effects. The present study demonstrated that H2S inhibited the interaction between the ER and mitochondrial apoptotic pathway. METHODS: This study investigated cardiac function, ultrastructural changes in the ER and mitochondria, apoptotic rate using TUNEL and the expression of ER stress-associated proteins and mitochondrial apoptotic proteins in cardiac tissues in STZ-induced type I diabetic rats treated with or without NaHS (donor of H2S)...
December 20, 2016: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27965206/prior-lactation-reduces-future-diabetic-risk-through-sustained-post-weaning-effects-on-insulin-sensitivity
#11
Harpreet Bajaj, Chang Ye, Anthony J Hanley, Phil W Connelly, Mathew Sermer, Bernard Zinman, Ravi Retnakaran
Breastfeeding ≥12 months is recommended for optimal infant nutrition but may hold maternal benefits, as well. Indeed, lactation has been associated with lower long-term risk of diabetes in the mother but the mechanism by which it imparts sustained post-weaning effects on glucose tolerance remains unclear. In this context, we postulated that lactation potentially could induce post-weaning beneficial effects on glucose tolerance by modifying the natural history of insulin sensitivity and/or pancreatic beta-cell function over time...
December 13, 2016: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27965205/postnatal-treatment-with-metyrapone-attenuates-the-effects-of-diet-induced-obesity-in-female-rats-exposed-to-early-life-stress
#12
Margaret O Murphy, Joseph B Herald, Caleb T Wills, Stanley G Unfried, Dianne M Cohn, Analia S Loria
This study tested the hypothesis that female rats pups exposed to maternal separation (MatSep), a model of early life stress, display an exacerbated response to diet-induced obesity compared to male rats. Also, we tested whether postnatal treatment with metyrapone (MTP), a corticosterone synthase inhibitor, would attenuate this phenotype. MatSep was performed in WKY offspring by separation from the dam (3 hr/day, postnatal day 2-14). Upon weaning, male and female rats were placed on regular chow (ND, 18% kcal fat) or HFD (60% kcal fat)...
December 13, 2016: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27965204/effects-of-paternal-obesity-on-growth-and-adiposity-of-male-rat-offspring
#13
Virginie Lecomte, Christopher A Maloney, Kristy W Wang, Margaret J Morris
Emerging evidence suggests that paternal obesity plays an important role in offspring health. We previously showed that female offspring from high fat diet (HFD) fed male rats develop glucose intolerance due to impaired insulin secretion. Here, we focussed on the health outcomes of male offspring from HFD fed fathers. Male Sprague Dawley rats (3 week-old) were fed control diet (CD-F0) or HFD (HFD-F0) for 12 weeks before mating with control fed females. Male offspring fed control diet were studied at 8 weeks and 6 months...
December 13, 2016: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27965203/myostatin-propeptide-mutation-of-the-hypermuscular-compact-mice-decreases-the-formation-of-myostatin-and-improves-insulin-sensitivity
#14
Tamas Kocsis, Gyorgy Trencsenyi, Kitti Szabo, Julia Aliz Baan, Geza Muller, Luca Mendler, Ildiko Garai, Hans Reinauer, Ferenc Deak, Laszlo Dux, Aniko Keller-Pinter
The TGF-β family member myostatin (growth/differentiation factor-8, GDF-8) is a negative regulator of skeletal muscle growth. The hypermuscular Compact mice carry the 12-bp Mstn(Cmpt-dl1Abc) deletion in the sequence encoding the propeptide region of the precursor promyostatin and additional modifier genes of the Compact genetic background contribute to determine the full expression of the phenotype. In this study, by using mice strains carrying mutant or wild-type myostatin alleles with Compact genetic background, and non-mutant myostatin with wild-type background we studied separately the effect of the Mstn(Cmpt-dl1Abc) mutation or the Compact genetic background on morphology, metabolism and signaling...
December 13, 2016: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27923809/role-of-autonomic-nervous-system-in-chronic-cns-mediated-antidiabetic-action-of-leptin
#15
Alexandre A da Silva, John E Hall, Sydney P Moak, Jackson Browning, Haley J Houghton, Giovana C Micheloni, Jussara M do Carmo
This study tested whether chronic ganglionic blockade or hepatic vagotomy attenuates the chronic CNS-mediated antidiabetic and cardiovascular effects of leptin. Male Sprague-Dawley rats were instrumented with telemetry probes and arterial and venous catheters for determination of blood pressure (BP), heart rate (HR), blood sampling and intravenous (IV) infusions. An intracerebroventricular (ICV) cannula was placed into the brain lateral ventricle for infusion of leptin or vehicle. After control measurements, streptozotocin (STZ) was injected IV (50 mg/kg) to induce diabetes and 5 days later leptin (n=6) or saline vehicle (n=5) was infused ICV for 12 days via osmotic pumps...
December 6, 2016: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27923808/ucp1-inhibition-in-cidea-overexpressing-mice-is-physiologically-counteracted-by-brown-adipose-tissue-hyperrecruitment
#16
Alexander W Fischer, Irina G Shabalina, Charlotte L Mattsson, Gustavo Abreu-Vieira, Barbara Cannon, Jan Nedergard, Natasa Petrovic
Cidea is a gene highly expressed in thermogenesis-competent (UCP1-containing) adipose cells, both brown and brite/beige. Here we initially demonstrate a remarkable adipose-depot specific regulation of Cidea expression. In classical brown fat, Cidea mRNA is expressed continuously and invariably, irrespective of tissue recruitment. However, Cidea protein levels are regulated posttranscriptionally, being conspicuously induced in the thermogenically recruited state. In contrast, in brite fat, Cidea protein levels are regulated at the transcriptional level, and Cidea mRNA and protein levels are proportional to tissue "briteness"...
December 6, 2016: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27899343/long-term-high-fat-diet-induces-hippocampal-microvascular-insulin-resistance-and-cognitive-dysfunction
#17
Zhuo Fu, Jing Wu, Tanseli Nesil, Ming D Li, Kevin W Aylor, Zhenqi Liu
Insulin action on hippocampus improves cognitive function and obesity and type 2 diabetes are associated with decreased cognitive function. Cerebral microvasculature plays a critical role in maintaining cerebral vitality and function by supplying nutrients, oxygen and hormones such as insulin to cerebral parenchyma including hippocampus. In skeletal muscle insulin actively regulates microvascular opening and closure and this action is impaired in the insulin resistant states. To examine insulin's action on hippocampal microvasculature and parenchyma and the impact of diet-induced obesity we determined cognitive function, and microvascular insulin responses, parenchyma insulin responses and capillary density in the hippocampus in 2-month and 8-month rats on chow diet and 8-month rats on long-term high-fat diet (6 months)...
November 29, 2016: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27894066/obesity-associated-extracellular-mtdna-activates-central-tgf%C3%AE-pathway-to-cause-blood-pressure-increase
#18
Alberto Ale, Yalin Zhang, Cheng Han, Dongsheng Cai
Hypothalamic inflammation was recently found to mediate obesity-related hypertension, but the responsible upstream mediators remain unexplored. In this study, we show that dietary obesity is associated with extracellular release of mitochondrial DNA (mtDNA) into the cerebrospinal fluid, and that central delivery of mtDNA mimics TGFβ excess to activate downstream signaling pathways. Physiological study reveals that central administration of mtDNA or TGFβ are both sufficient to cause hypertension in mice. Knockout of the TGFβ receptor in pro-opiomelanocortin neurons counteracts the hypertensive effect of not only TGFβ but mtDNA excess, while the hypertensive action of central mtDNA can be blocked pharmacologically by a TGFβ receptor antagonist or genetically by TGFβ receptor knockout...
November 15, 2016: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27894063/loss-of-glutaredoxin-3-impedes-mammary-lobuloalveolar-development-during-pregnancy-and-lactation
#19
Khanh Pham, Jie Dong, Xiqian Jiang, Ying Qu, Han Yu, Yisheng Yang, Walter Olea, Juan C Marini, Lawrence Chan, Jin Wang, Xander H T Wehrens, Xiaojiang Cui, Yi Li, Darryl L Hadsell, Ninghui Cheng
Mammalian glutaredoxin 3 (Grx3) has been shown to be important for regulating cellular redox homeostasis in the cell. Our previous studies indicate that Grx3 is significantly overexpressed in various human cancers including breast cancer and demonstrate that Grx3 controls cancer cell growth and invasion by regulating ROS and NF-κB signaling pathways. However, it remains to be determined whether Grx3 is required for normal mammary gland development and how it contributes to epithelial cell proliferation and differentiation in vivo In the present study, we examined Grx3 expression in different cell types within the developing mouse mammary gland (MG) and found enhanced expression of Grx3 at pregnancy and lactation stages...
November 15, 2016: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27780819/light-load-resistance-exercise-increases-muscle-protein-synthesis-and-hypertrophy-signaling-in-elderly-men
#20
Jakob Agergaard, Jacob Bulow, Jacob K Jensen, Søren Reitelseder, Micah J Drummond, Peter Schjerling, Thomas Scheike, Anja Serena, Lars Holm
INTRODUCTION: The present study investigated whether well-tolerated light-load resistance exercise (LL-RE) affects skeletal muscle fractional synthetic rate (FSR) and anabolic intracellular signaling as a way to counteract age-related loss of muscle mass. METHODS: Untrained healthy men (age: +65 yrs) were subjected to 13 hours supine rest. After 21/2 hours of rest, unilateral LL-RE was conducted consisting of leg extensions (10 sets, 36 repetitions) at 16% 1RM. Subsequently, the subjects were randomized to oral intake of PULSE (4g whey protein/hour; N=10), BOLUS (28g whey protein at 0 hours and 12g whey protein at 7 hours post-exercise; N=10) or placebo (4g maltodextrin/hour; N=10)...
October 25, 2016: American Journal of Physiology. Endocrinology and Metabolism
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