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American Journal of Physiology. Endocrinology and Metabolism

Kristen E Syring, Travis J Cyphert, Thomas C Beck, Charles R Flynn, Nicholas A Mignemi, Owen P McGuinness
Bile acids are involved in the emulsification and absorption of dietary fats as well as acting as signaling molecules. Recently, bile acid signaling through farnesoid X receptor (FXR) and G Protein-Coupled Bile Acid Receptor (TGR5) has been reported to elicit changes in not only bile acid synthesis but also metabolic processes including altering gluconeogenic gene expression and energy expenditure. A role for bile acids in glucose metabolism is also supported by a correlation between changes in the metabolic state of patients (i...
February 19, 2019: American Journal of Physiology. Endocrinology and Metabolism
Daniil V Popov, Pavel A Makhnovskii, Elena I Shagimardanova, Guzel R Gazizova, Evgeny A Lysenko, Oleg A Gusev, Olga L Vinogradova
Reduction in daily activity leads to dramatic metabolic disorders, while regular aerobic exercise training is effective for preventing this problem. The purpose of this study was to identify genes that are directly related to contractile activity in human skeletal muscle, regardless of the level of fitness. Transcriptome changes after the one-legged knee extension exercise in exercised and contralateral non-exercised vastus lateralis muscle of 7 males were evaluated by RNA-seq. Transcriptome change at baseline after 2 months of aerobic training (5/wk, 1 h/day) was evaluated as well...
February 19, 2019: American Journal of Physiology. Endocrinology and Metabolism
Arash Bandegan, Glenda Courtney-Martin, Mahroukh Rafii, Paul B Pencharz, Peter Wr Lemon
Despite studies indicating increased protein requirements in endurance-trained (ET) individuals, the Institute of Medicine has concluded, that "no additional dietary protein is suggested for healthy adults undertaking resistance or endurance exercise" and the controversy regarding exercise effects on protein requirements continues. The objective of this study was to determine the dietary protein requirement of healthy young ET men (≥1 y training experience) 24h post-exercise (to minimize any acute effects of the previous training session) by measuring the oxidation of ingested L-[1-13 C] phenylalanine to 13 CO2 in response to graded intakes of protein [Indicator Amino Acid Oxidation (IAAO) Technique]...
February 19, 2019: American Journal of Physiology. Endocrinology and Metabolism
Pernille Hojman, Camilla Brolin, Nynne Nørgaard-Christensen, Christine Dethlefsen, Britt Lauenborg, Cecilie K Olsen, Mette-Marie Åbom, Thomas O Krag, Julie Gehl, Bente Klarlund Pedersen
BACKGROUND: IL-6 is secreted from muscles to the circulation during high intensity and long duration exercise, where muscle-derived IL-6 works as an energy sensor to increase release of energy substrates from liver and adipose tissues. Here, we investigated the mechanism involved in the exercise-mediated surge in IL-6 during exercise. METHODS: Using interval-based cycling in healthy young men, swimming exercise in mice and electrical stimulation of primary human muscle cells, we explored the role of lactate production in muscular IL-6 release during exercise...
February 19, 2019: American Journal of Physiology. Endocrinology and Metabolism
Mark W Pataky, Carmen S Yu, Yilin Nie, Edward B Arias, Manak Singh, Christopher L Mendias, Robert J Ploutz-Snyder, Gregory D Cartee
Insulin-stimulated glucose uptake (GU) by skeletal muscle is enhanced several hours after acute exercise in rats with normal or reduced insulin sensitivity. Skeletal muscle is composed of multiple fiber types, but exercise's effect on fiber type-specific insulin-stimulated GU in insulin-resistant muscle was previously unknown. Male rats were fed a high-fat diet (HFD; 2-weeks) and either sedentary (SED) or exercised (2h exercise). Other low-fat diet-fed (LFD) rats remained SED. Rats were studied immediately-post exercise (IPEX) or 3h post-exercise (3hPEX)...
February 12, 2019: American Journal of Physiology. Endocrinology and Metabolism
Kuei-Pin Huang, Charlotte C Ronveaux, Guillaume de Lartigue, Nori Geary, Lori Asarian, Helen E Raybould
Deletion of the leptin receptor from vagal afferent neurons (VAN) using a conditional deletion (Nav1.8/LepRfl/fl ) results in an obese phenotype with increased food intake and lack of exogenous cholecystokinin (CCK)-induced satiation in male mice. Female mice are partially protected from weight gain and increased food intake in response to ingestion of high-fat (HF) diets. However, whether lack of leptin signaling in VAN leads to an obese phenotype or disruption of hypothalamic-pituitary-gonadal axis function in female mice is unclear...
February 12, 2019: American Journal of Physiology. Endocrinology and Metabolism
Melanie Cree-Green, Anne-Marie Carreau, Haseeb Rahat, Yesenia Garcia-Reyes, Bryan C Bergman, Laura Pyle, Kristen J Nadeau
Polycystic Ovarian Syndrome (PCOS) is associated with insulin resistance (IR) and altered muscle mitochondrial oxidative phosphorylation. IR in adults with obesity and diabetes is associated with changes in amino acid, free fatty acid (FFA) and mitochondrial acylcarnitine (AC) metabolism. We sought to determine if these metabolites are associated with IR and/or androgens in youth-onset PCOS. We enrolled obese girls with PCOS [n = 15, 14.5 ± 1.6 years, BMI %ile 98.5 ± 1.0] and without PCOS [n = 6, 13.2 ± 1...
February 12, 2019: American Journal of Physiology. Endocrinology and Metabolism
Amar B Singh, Chin Fung K Kan, Fredric B Kraemer, Raymond A Sobel, Jingwen Liu
Long-chain acyl-CoA synthetase 4 (ACSL4) has a unique substrate specificity for arachidonic acid (AA). Hepatic ACSL4 is coregulated with the phospholipid remodeling enzyme lysophosphatidylcholine acyltransferase 3 (LPCAT3) by PPARd to modulate plasma triglyceride metabolism. In this study, we investigated the acute effects of hepatic ACSL4 deficiency on lipid metabolism in adult mice fed a high-fat diet (HFD). Adenovirus-mediated expression of a mouse ACSL4 shRNA (Ad-shAcsl4) in the liver of HFD-fed mice led to a 43% reduction of hepatic arachidonoyl-CoA synthetase activity and a 53% decrease in ACSL4 protein levels as compared to mice receiving control adenovirus (Ad-shLacZ)...
February 5, 2019: American Journal of Physiology. Endocrinology and Metabolism
Maximilian Kleinert, Kirstine N Bojsen-Møller, Nils B Jørgensen, Maria S Svane, Christoffer Martinussen, Bente Kiens, Jorgen F P Wojtaszewski, Sten Madsbad, Erik A Richter, Christoffer Clemmensen
Bariatric surgery results in marked body weight loss and improves type 2 diabetes in most patients with obesity. The growth differentiation factor 15 (GDF15) has recently emerged as a novel satiety factor. To begin to understand whether GDF15 is involved in mediating the effects of bariatric surgery on body weight and glycaemia in humans, we measured plasma GDF15 in patients with obesity (n = 25) and in patients with obesity and diabetes (n = 22) before and after Roux-en-Y gastric bypass (RYGB) surgery. GDF15 was increased 1 week after RYGB compared with before surgery (689 ± 45 pg/ml vs...
February 5, 2019: American Journal of Physiology. Endocrinology and Metabolism
Ruth B S Harris
Previous studies suggest that weight loss occurs when leptin receptors in both the forebrain and hindbrain are activated. Experiments described here tested whether this integration is mediated through a neural connection or by leptin diffusion through the subarachanoid space. If the hypothalamus and hindbrain communicated through a neural pathway, then a very low dose of leptin infused directly into the nucleus of the solitary tract (NTS) would enhance the response to third ventricle (3V) leptin, but would have no effect if infused into the fourth ventricle (4V)...
February 5, 2019: American Journal of Physiology. Endocrinology and Metabolism
Shilpa R Nagarajan, Moumita Paul-Heng, James R Krycer, Daniel Fazakerley, Alexandra F Sharland, Andrew J Hoy
The liver is a critical tissue for maintaining glucose, fatty acid and cholesterol homeostasis. Primary hepatocytes represent the gold standard for studying the mechanisms controlling hepatic glucose, lipid and cholesterol metabolism in vitro. However, access to primary hepatocytes can be limiting and therefore other immortalized hepatocyte models are commonly used. Here we describe substrate metabolism of cultured AML12, IHH and PH5CH8 cells, hepatocellular carcinoma-derived HepG2s and primary mouse hepatocytes (PMHs) to identify which of these cell lines most accurately phenocopy PMH basal and insulin-stimulated metabolism...
January 29, 2019: American Journal of Physiology. Endocrinology and Metabolism
Matthew T Dickerson, Prasanna K Dadi, Molly K Altman, Kenneth R Verlage, Ariel S Thorson, Kelli L Jordan, Nicholas C Vierra, Gautami Amarnath, David A Jacobson
Pancreatic α-cells exhibit oscillations in cytosolic Ca2+ (Ca2+ c ), which control pulsatile glucagon (GCG) secretion. However, the mechanism(s) that modulate α-cell Ca2+ c oscillations have not been elucidated. As β-cell Ca2+ c oscillations are regulated in part by Ca2+ -activated K+ (Kslow ) currents, this work investigated the role of Kslow in α-cell Ca2+ handling and GCG secretion. Alpha-cells displayed Kslow currents that were dependent on Ca2+ influx through L- and P/Q-type voltage-dependent Ca2+ channels (VDCCs) as well as Ca2+ released from endoplasmic reticulum stores...
January 29, 2019: American Journal of Physiology. Endocrinology and Metabolism
Kefan Zhang, Miaomiao Wang, Yingjiang Li, Chunping Li, Shaidi Tang, Xiuxia Qu, Ninghan Feng, Yu Wu
Parathyroid hormone (PTH) and its related peptide (PTH related peptide 1-34) are one of FDA-approved bone-promoting drugs for age-related osteoporosis. Treatment with PTH stimulates bone formation. But the molecular mechanisms of PTH-mediated osteoblast differentiation and cell proliferation are still not completely understood. In this study, we showed that PTH induced endoplasmic reticulum (ER) stress in osteoblasts through the PERK-EIF2α-ATF4-signaling pathway. After separately blocking PERK-EIF2α-ATF4 signaling with two different inhibitors (AMG'44 and ISRIB), or specific small interfering RNA for PERK and ATF4, the following targets were all downregulated: expression of osteoblast differentiation markers (Runx2, Alp, Col1a1 and Ocn), cell proliferation markers (CyclinE, CyclinD and CDC2), amino acid import (Glyt1) and metabolism-related genes (Asns)...
January 22, 2019: American Journal of Physiology. Endocrinology and Metabolism
Chih-Wei Wu, Chun-Ying Hung, Hajime Hirase, You-Lin Tain, Wei-Chia Lee, Julie Y H Chan, Mu-Hui Fu, Lee-Wei Chen, Wen-Chung Liu, Chih-Kuang Liang, Ying-Hao Ho, Yu Chih Kung, Steve Leu, Kay Li-Hui Wu
Excessive maternal high fructose diet (HFD) during pregnancy and lactation has been reported to cause metabolic disorders in the offspring. Whether the infant's brain metabolism is disturbed by maternal HFD is largely unknown. Brain energy metabolism is elevated dramatically during fetal and postnatal development, whereby maternal nutrition is a key factor that to determine cellular metabolism. Astrocytes, a non-neuronal cell type in the brain, are considered to support high energy demands of neurons by supplying lactate...
January 22, 2019: American Journal of Physiology. Endocrinology and Metabolism
Li Nie, You-Bo Zhao, Dan Zhao, Yun Long, Yi Lei, Min Liu, Yi-Cheng Wang, Xue-Qin Zhang, Jin-Hu Zhang, Dong-Zhi Yuan, Limin Yue
To investigate the role of progesterone-induced miR-152 in early embryonic development and implantation by regulating GLUT3 in endometrial epithelium. qRT-PCR was used to detect the expression of miR-152, GLUT1 and GLUT3 in the endometrial epithelial cells of female mice. GLUT1 and GLUT3 proteins were detected by immunohistochemical staining in the mouse endometrial epithelium. Bioinformatics prediction associated with a luciferase assay was performed to determine whether GLUT1 and GLUT3 are target genes of miR-152...
January 22, 2019: American Journal of Physiology. Endocrinology and Metabolism
Marlou L Dirks, Joey S J Smeets, Andrew M Holwerda, Imre W K Kouw, Gabriel N Marzuca-Nassr, Annemie P Gijsen, Graham P Holloway, Lex B Verdijk, Luc J C van Loon
Short periods of bed rest lead to the loss of muscle mass and quality. It has been speculated that dietary feeding pattern may impact upon muscle protein synthesis rates and, therefore, modulate the loss of muscle mass and quality. We subjected 20 healthy men (age: 25±1 y, BMI: 23.8±0.8 kg·m-2 ) to one week of strict bed rest with intermittent (4 meals/day) or continuous (24 h/day) enteral tube feeding. Participants consumed deuterium oxide for 7 days prior to bed rest and throughout the 7-day bed rest period...
January 15, 2019: American Journal of Physiology. Endocrinology and Metabolism
Yu Shao, Emily Wichern, Paul J Childress, Michele Adaway, Jagannath Misra, Angela Klunk, David B Burr, Ronald C Wek, Amber L Mosley, Yunlong Liu, Alexander G Robling, Nickolay Brustovetsky, James Hamilton, Kylie Jacobs, Deepak Vashishth, Keith R Stayrook, Matthew R Allen, Joseph M Wallace, Joseph P Bidwell
A goal of osteoporosis therapy is to restore lost bone with structurally sound tissue. Mice lacking the transcription factor Nuclear Matrix Protein 4 (Nmp4, Zfp384, Ciz, ZNF384) respond to several classes of osteoporosis drugs with enhanced bone formation compared to wild type (WT) animals. Nmp4-/- mesenchymal stem/progenitor cells (MSPCs) exhibit an accelerated and enhanced mineralization during osteoblast differentiation. To address the mechanisms underlying this hyper-anabolic phenotype, we carried out RNA-sequencing and molecular and cellular analyses of WT and Nmp4-/- MSPCs during osteogenesis to define pathways and mechanisms associated with elevated matrix production...
January 15, 2019: American Journal of Physiology. Endocrinology and Metabolism
Annamaria Morelli, Sandra Filippi, Paolo Comeglio, Erica Sarchielli, Ilaria Cellai, Marco Pallecchi, Gianluca Bartolucci, Giovanna Danza, Giulia Rastrelli, Chiara Corno, Giulia Guarnieri, Elisa Fuochi, Linda Vignozzi, Mario Maggi
Metabolic syndrome (MetS) clusters cardiovascular and metabolic risk factors, along with hypogonadism (HG) and erectile dysfunction (ED). Lifestyle modifications including physical exercise (PhyEx) are well-known treatments for this condition. In this study, we analyzed the effect of PhyEx on hypothalamus-pituitary-testis axis and erectile function using an animal MetS model, previously established in rabbits fed a high fat diet (HFD). Rabbits fed a regular diet (RD) were used as controls. A subset of both groups was trained on a treadmill...
January 15, 2019: American Journal of Physiology. Endocrinology and Metabolism
Purnima Gurung, Karine Moussa, Beverley Adams-Huet, Sridevi Devaraj, Ishwarlal Jialal
Metabolic Syndrome (MetS) affects 35% of American adults > 40 years and portends an increased risk for both cardiovascular disease (ASCVD) and diabetes. The role of mast cells in the pro-inflammatory state of MetS is not well elucidated. We propose that mast cells in subcutaneous adipose tissue (SAT) of MetS (no diabetes or ASCVD) patients contribute to insulin resistance and inflammation. Matched controls (n=15) and nascent MetS (n=19) subjects were recruited from Sacramento, CA and selected based on ATP III criteria...
January 8, 2019: American Journal of Physiology. Endocrinology and Metabolism
Jacquelyn M Walejko, Andrew Antolic, Jeremy P Koelmel, Timothy J Garrett, Arthur S Edison, Maureen Keller-Wood
Our laboratory has previously shown in an ovine model of pregnancy that abnormal elevations in maternal cortisol during late gestation lead to increased fetal cardiac arrhythmias and mortality during peripartum. Furthermore, transcriptomic analysis of the fetal heart suggested alterations in TCA cycle intermediates and lipid metabolites in animals exposed to excess cortisol in utero. Therefore, we utilized a sheep model of pregnancy to determine how chronic increases in maternal cortisol alter maternal and fetal serum prior to birth and neonatal cardiac metabolites and lipids at term...
January 8, 2019: American Journal of Physiology. Endocrinology and Metabolism
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