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American Journal of Physiology. Endocrinology and Metabolism

Yueshui Zhao, Xue Gu, Ningyan Zhang, Mikhail G Kolonin, Zhiqiang An, Kai Sun
Endotrophin is a cleavage product of collagen 6 (Col6) in adipose tissue (AT). Previously, we demonstrated that endotrophin serves as a costimulator to trigger fibrosis and inflammation within the unhealthy AT milieu. However, how endotrophin affects lipid storage and breakdown in AT and how different cell types in AT respond to endotrophin stimulation remain unknown. In the current study, by using a doxycycline (Dox)-inducible mouse model, we observed significant upregulation of adipogenic genes in the WAT of endotrophin Tg mice...
October 11, 2016: American Journal of Physiology. Endocrinology and Metabolism
Il-Young Kim, Sanghee Park, Ting-Heng Chou, Justin R Trombold, Edward F Coyle
The interaction of prolonged sitting with physical exercise for maintaining health is unclear. We tested the hypothesis that prolonged siting would have a deleterious effect on postprandial plasma lipemia (PPL, postprandial plasma triglycerides) and abolish the ability of an acute exercise bout to attenuate PPL. Seven healthy young men performed three interventions over 5 days (D1-5) in a randomized crossover design with > 1 week between interventions: 1) sitting >14h/d with hypercaloric energy balance (SH), 2) sitting >14h/d with net energy balance (SB), and 3) active walking/standing with net energy balance (WB) and sitting 8...
October 4, 2016: American Journal of Physiology. Endocrinology and Metabolism
Hiroaki Kimura, Tadayoshi Karasawa, Fumitake Usui, Akira Kawashima, Yuka Endo, Motoi Kobayashi, Ai Sadatomo, Jun Nakamura, Yusaku Iwasaki, Toshihiko Yada, Hiroko Tsutsui, Tadashi Kasahara, Masafumi Takahashi
Caspase-1 is a cysteine protease responsible for the processing of the proinflammatory cytokine interleukin-1β and activated by the formation of inflammasome complexes. Although several investigations have found a link between diet-induced obesity and caspase-1, the relationship of remains controversial. Here, we found that mice deficient in caspase-1 were susceptible to high-fat diet-induced obesity with increased adiposity as well as normal lipid and glucose metabolism. Caspase-1 deficiency clearly promoted the infiltration of inflammatory macrophages and increased the production of C-C motif chemokine ligand 2 (CCL2) in the adipose tissue...
October 4, 2016: American Journal of Physiology. Endocrinology and Metabolism
William J Smiles, Evelyn B Parr, Vernon G Coffey, Orly Lacham-Kaplan, John A Hawley, Donny M Camera
Alcohol ingestion decreases post-exercise rates of muscle protein synthesis, but the mechanism(s) (e.g., increased protein breakdown) underlying this observation are unknown. Autophagy is an intracellular "recycling" system required for homeostatic substrate and organelle turnover; its dysregulation may provoke apoptosis and lead to muscle atrophy. We investigated the acute effects of alcohol ingestion on autophagic cell signaling responses to a bout of concurrent (combined resistance- and endurance-based) exercise...
September 27, 2016: American Journal of Physiology. Endocrinology and Metabolism
Jordan Gaines, Alexandros N Vgontzas, Julio Fernandez-Mendoza, Susan L Calhoun, Fan He, Duanping Liao, Marjorie D Sawyer, Edward O Bixler
Only a handful of studies, primarily in clinical samples, have reported an association between obesity, inflammation, and obstructive sleep apnea (OSA) in children and adolescents. No studies, however, have examined the pathogenetic link between visceral adiposity, systemic inflammation, and incident OSA in a large general population sample using objective measures of sleep and body fat. Adolescents (n=392; mean age 17.0±2.2y, 54.0% male) from the Penn State Child Cohort (PSCC) underwent 9-hour overnight polysomnography; a DXA scan to assess body fat distribution; and a single fasting blood draw for the assessment of plasma interleukin-6 (IL-6), IL-6 soluble receptor (IL-6 sR), tumor necrosis factor alpha (TNFα), tumor necrosis factor receptor 1A (TNFR1), C-reactive protein (CRP), leptin, and adiponectin levels via ELISA...
September 20, 2016: American Journal of Physiology. Endocrinology and Metabolism
Sheng-Ping Wang, Dan Zhou, Zuliang Yao, Santhosh Satapati, Ying Chen, Natalie A Daurio, Aleksandr Petrov, Xiaolan Shen, Daniel Metzger, Wu Yin, Andrea R Nawrocki, George J Eiermann, Joyce Hwa, Craig Fancourt, Corey Miller, Kithsiri Herath, Thomas P Roddy, Deborah Slipetz, Mark D Erion, Stephen F Previs, David E Kelley
Aberrant regulation of glucose production makes a critical contribution to the impaired glycemic control that is observed in Type 2 diabetes. Although isotopic tracer methods have proven to be informative in quantifying the magnitude of such alterations, it is presumed that one must rely on venous access to administer glucose tracers which therein presents obstacles for the routine application of tracer methods in rodent models. Since intraperitoneal injections are readily used to deliver glucose challenges and/or dose potential therapeutics, we hypothesized that this route could also be used to administer a glucose tracer...
September 20, 2016: American Journal of Physiology. Endocrinology and Metabolism
Kristie I Aamodt, Radhika Aramandla, Judy Brown, Nathalie Fiaschi-Taesch, Peng Wang, Andrew F Stewart, Marcela Brissova, Alvin C Powers
Numerous compounds stimulate rodent β cell proliferation; however, translating these findings to human β cells remains a challenge. To examine human β cell proliferation in response to such compounds, we developed a medium-throughput in vitro method of quantifying adult human β cell proliferation markers. This method is based on high-content imaging of dispersed islet cells seeded in 384-well plates and automated cell counting that identifies fluorescently-labeled β cells with high specificity using both nuclear and cytoplasmic markers...
September 13, 2016: American Journal of Physiology. Endocrinology and Metabolism
Nicolas J Pillon, Kenny L Chan, Shitian Zhang, Marios Mejdani, Maya R Jacobson, Alexandre Ducos, Philip J Bilan, Wenyan Niu, Amira Klip
Obesity is associated with metabolic tissue infiltration by monocyte-derived macrophages. Saturated fatty acids contribute to pro-inflammatory gene induction in tissue-embedded immune cells. However, it is unknown how circulating monocytes -the macrophage precursors- react to high fat environments. In macrophages, saturated fatty acids activate inflammatory pathways and, notably, prime caspase-associated inflammasomes. Inflammasome-activated IL1β contributes to type 2 diabetes. We hypothesized that a) human monocytes from obese patients show caspase activation, and b) fatty acids trigger this response and consequent release of IL1β/IL18...
September 13, 2016: American Journal of Physiology. Endocrinology and Metabolism
Alyssa Charrier, Li Wang, Erin J Stephenson, Siddharth V Ghanta, Chih-Wei Ko, Colleen M Croniger, Dave Bridges, David A Buchner
The peroxisome proliferator-activated receptor (PPAR) family of nuclear receptors are central to the pathophysiology and treatment of metabolic disease through their ability to regulate the expression of genes involved in glucose homeostasis, adipogenesis, and lipid metabolism. However, the mechanism by which PPAR is regulated remains incompletely understood. We generated a transgenic mouse strain (ZFP-TG) that overexpressed Zfp407 primarily in muscle and heart. Transcriptome analysis by RNA-Seq identified 1,300 differentially expressed genes in the muscle of ZFP-TG mice, among which PPAR target genes were significantly enriched...
September 13, 2016: American Journal of Physiology. Endocrinology and Metabolism
Gregory D Cartee, Edward B Arias, Carmen S Yu, Mark W Pataky
One exercise session can induce subsequently elevated insulin sensitivity that is largely attributable to greater insulin-stimulated glucose uptake by skeletal muscle. Because skeletal muscle is a heterogeneous tissue comprised of diverse fiber types, our primary aim was to determine exercise effects on insulin-independent and insulin-dependent glucose uptake by single fibers of different fiber types. We hypothesized that each fiber type featuring elevated insulin-independent glucose uptake immediately post-exercise (IPEX) would be characterized by increased insulin-dependent glucose uptake at 3...
September 6, 2016: American Journal of Physiology. Endocrinology and Metabolism
Brandon J Shad, Janice L Thompson, Leigh Breen
Our aim was to assess whether the muscle protein synthesis (MPS) response to acute exercise and/or amino acid-based nutrition is attenuated in older compared with young individuals. A systematic review was conducted on studies that directly examined the influence of age on the MPS response to exercise and/or amino acid-based nutrition. Each study arm was synthesised and reported as providing sufficient or insufficient 'evidence of age-related muscle anabolic resistance'. Subsequently, three models were established to compare age-related differences in the MPS response to different anabolic stimuli...
August 23, 2016: American Journal of Physiology. Endocrinology and Metabolism
Bettina K Wölnerhanssen, Anne Christin Meyer Gerspach, Christoph Beglinger
No abstract text is available yet for this article.
October 1, 2016: American Journal of Physiology. Endocrinology and Metabolism
Angela Bonnema, Peter DeCock, Alex Eapen, Douwina Bosscher
No abstract text is available yet for this article.
October 1, 2016: American Journal of Physiology. Endocrinology and Metabolism
Adriana D Hernandez-García, Daniel A Columbus, Rodrigo Manjarín, Hanh V Nguyen, Agus Suryawan, Renán A Orellana, Teresa A Davis
Sepsis disrupts skeletal muscle proteostasis and mitigates the anabolic response to leucine (Leu) in muscle of mature animals. We have shown that Leu stimulates muscle protein synthesis (PS) in healthy neonatal piglets. To determine if supplemental Leu can stimulate PS and reduce protein degradation (PD) signaling in neonatal muscle during endotoxemia, overnight-fasted neonatal pigs were infused for 8 h with LPS or saline while plasma amino acids, glucose, and insulin were maintained at fasting levels during pancreatic-substrate clamps...
October 1, 2016: American Journal of Physiology. Endocrinology and Metabolism
Irena Týcová, Sylvie Dusilová Sulková, Jitka Štěpánková, Zdeněk Krejčík, Michaela Dostálová Merkerová, Viktor Stránecký, Petra Hrubá, Eva Girmanová, Marek Černoch, Květoslav Lipár, Tomáš Marada, Ctibor Povýšil, Ondřej Viklický
Secondary hyperparathyroidism is a well-known complication of end-stage renal disease (ESRD). Both nodular and diffuse parathyroid hyperplasia occur in ESRD patients. However, their distinct molecular mechanisms remain poorly understood. Parathyroid tissue obtained from ESRD patients who had undergone parathyroidectomy was used for Illumina transcriptome screening and subsequently for discriminatory gene analysis, pathway mapping, and gene annotation enrichment analysis. Results were further validated using quantitative RT-PCR on the independent larger cohort...
October 1, 2016: American Journal of Physiology. Endocrinology and Metabolism
Zhi-Jun Ou, Jing Chen, Wei-Ping Dai, Xiang Liu, Yin-Ke Yang, Yan Li, Ze-Bang Lin, Tian-Tian Wang, Ying-Ying Wu, Dan-Hong Su, Tian-Pu Cheng, Zhi-Ping Wang, Jun Tao, Jing-Song Ou
Endothelial dysfunction is a key early step in atherosclerosis. 25-Hydroxycholesterol (25-OHC) is found in atherosclerotic lesions. However, whether 25-OHC promotes atherosclerosis is unclear. Here, we hypothesized that 25-OHC, a proinflammatory lipid, can impair endothelial function, which may play an important role in atherosclerosis. Bovine aortic endothelial cells were incubated with 25-OHC. Endothelial cell proliferation, migration, and tube formation were measured. Nitric oxide (NO) production and superoxide anion generation were determined...
October 1, 2016: American Journal of Physiology. Endocrinology and Metabolism
Canjun Zeng, Helen Goodluck, Xuezhong Qin, Bo Liu, Subburaman Mohan, Weirong Xing
Leucine-rich repeat kinase-1 (Lrrk1) consists of ankyrin repeats (ANK), leucine-rich repeats (LRR), a GTPase-like domain of Roc (ROC), a COR domain, a serine/threonine kinase domain (KD), and WD40 repeats (WD40). Previous studies have revealed that knockout (KO) of Lrrk1 in mice causes severe osteopetrosis, and a human mutation of Lrrk1 leads to osteosclerotic metaphysial dysplasia. The molecular mechanism by which Lrrk1 regulates osteoclast function is unknown. In this study, we generated a series of Lrrk1 mutants and evaluated their ability to rescue defective bone resorption in Lrrk1-deficient osteoclasts by use of pit formation assays...
October 1, 2016: American Journal of Physiology. Endocrinology and Metabolism
E Matthew Morris, Grace M E Meers, Lauren G Koch, Steven L Britton, Justin A Fletcher, Xiaorong Fu, Kartik Shankar, Shawn C Burgess, Jamal A Ibdah, R Scott Rector, John P Thyfault
Rats selectively bred for high capacity running (HCR) or low capacity running (LCR) display divergence for intrinsic aerobic capacity and hepatic mitochondrial oxidative capacity, both factors associated with susceptibility for nonalcoholic fatty liver disease. Here, we tested if HCR and LCR rats display differences in susceptibility for hepatic steatosis after 16 wk of high-fat diets (HFD) with either 45% or 60% of kcals from fat. HCR rats were protected against HFD-induced hepatic steatosis, whereas only the 60% HFD induced steatosis in LCR rats, as marked by a doubling of liver triglycerides...
October 1, 2016: American Journal of Physiology. Endocrinology and Metabolism
Christine M Jewell, Kevin S Katen, Lisa M Barber, Crystal Cannon, Stavros Garantziotis, John A Cidlowski
The glucocorticoid receptor single-nucleotide polymorphism (SNP) N363S has been reported to be associated with metabolic syndrome, type 2 diabetes, and cardiovascular disease. Our aim was to determine how the N363S SNP modifies glucocorticoid receptor signaling in a healthy population of individuals prior to the onset of disease. We examined the function of the N363S SNP in a cohort of subjects from the general population of North Carolina. Eighteen N363S heterozygous carriers and 36 noncarrier, control subjects were examined for clinical and biochemical parameters followed by a low-dose dexamethasone suppression test to evaluate glucocorticoid responsiveness...
October 1, 2016: American Journal of Physiology. Endocrinology and Metabolism
Laurent Bultot, Thomas E Jensen, Yu-Chiang Lai, Agnete L B Madsen, Caterina Collodet, Samanta Kviklyte, Maria Deak, Arash Yavari, Marc Foretz, Sahar Ghaffari, Mohamed Bellahcene, Houman Ashrafian, Mark H Rider, Erik A Richter, Kei Sakamoto
AMP-activated protein kinase (AMPK) plays diverse roles and coordinates complex metabolic pathways for maintenance of energy homeostasis. This could be explained by the fact that AMPK exists as multiple heterotrimer complexes comprising a catalytic α-subunit (α1 and α2) and regulatory β (β1 and β2)- and γ (γ1, γ2, γ3)-subunits, which are uniquely distributed across different cell types. There has been keen interest in developing specific and isoform-selective AMPK-activating drugs for therapeutic use and also as research tools...
October 1, 2016: American Journal of Physiology. Endocrinology and Metabolism
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