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American Journal of Physiology. Endocrinology and Metabolism

Li-Hao Huang, Elaina M Melton, Haibo Li, Paul Sohn, DaeYoung Jung, Ching-Yi Tsai, Tian Ma, Hiroyuki Sano, HyeKyung Ha, Randall H Friedline, Jason K Kim, Edward Usherwood, Catherine Cy Chang, Ta-Yuan Chang
Macrophages are phagocytes that play important roles in health and diseases. Acyl-CoA:cholesterol acyltransferase 1 [ACAT1] converts cellular cholesterol to cholesteryl esters, and is expressed in many cell types. Unlike global Acat1 knockout [KO], myeloid-specific Acat1 KO [Acat1-M/-M ] does not cause overt abnormalities in mice. Here we performed analyses in age and sex matched Acat1-M/-M and wild-type mice on chow or Western diet, and discovered that Acat1-M/-M mice exhibit resistance to Western diet-induced obesity...
March 13, 2018: American Journal of Physiology. Endocrinology and Metabolism
Long The Nguyen, Hui Chen, Crystal Mak, Amgad Zaky, Carol Pollock, Sonia Saad
Recent studies indicate that SIRT1, an important metabolic sensor and regulator of lifespan, plays a mechanistic role in maternal obesity-induced programming of metabolic disorders in the offspring. In this study we investigate whether SIRT1 activation in early childhood can mitigate metabolic disorders due to maternal and postnatal high-fat feeding in mice. Male offspring born to chow-fed (MC) or high-fat diet-fed dams (MHF) were weaned onto postnatal chow or high-fat diet and treated with SRT1720 (SRT, 25mg/kg/2days i...
March 13, 2018: American Journal of Physiology. Endocrinology and Metabolism
Agnete B Madsen, Jonas R Knudsen, Carlos Henriquez-Olguin, Yeliz Angin, Kristien J Zaal, Lykke Sylow, Peter Schjerling, Evelyn Ralston, Thomas E Jensen
Studies in skeletal muscle cell cultures suggest that the cortical actin cytoskeleton is a major requirement for insulin-stimulated glucose transport, implicating the β-actin isoform which, in many cell types, is the main actin isoform. However, it is not clear that β-actin plays such a role in mature skeletal muscle. Neither dependency of glucose transport on β-actin nor actin reorganization upon glucose transport have been tested in mature muscle. To investigate the role of β-actin in fully differentiated muscle, we have performed a detailed characterization of wildtype and muscle-specific β-actin knockout (KO) mice...
March 13, 2018: American Journal of Physiology. Endocrinology and Metabolism
Calyn B Maske, Gregory C Loney, Nicole Lilly, Sarah J Terrill, Diana L Williams
The idea that gut-derived satiation signals influence food reward has recently gained traction, but this hypothesis is largely based on studies focused on neural circuitry, not the peripherally released signals. Here, we directly tested the hypothesis that intragastric (IG) nutrient infusion can suppress motivation for food. In a series of experiments, IG sucrose infusion (15 kcal) significantly and reliably reduced operant responding for a sucrose reward on a progressive ratio (PR) schedule. Moreover, food deprivation for 24 h before the test session did not prevent the suppressive effect of nutrients...
March 13, 2018: American Journal of Physiology. Endocrinology and Metabolism
Ying Chen, Olga Berejnaia, Jinqi Liu, Sheng-Ping Wang, Natalie A Daurio, Wu Yin, Rafael Mayoral, Aleksandr Petrov, Takhar Kasumov, Guo-Fang Zhang, Stephen F Previs, David E Kelley, David G McLaren
Numerous studies have implicated dyslipidemia as a key factor in mediating insulin resistance. Ceramides have received special attention since their levels are inversely associated with normal insulin signaling and positively associated with factors that are involved in cardiometabolic disease. Despite the growing literature surrounding ceramide biology, there are limited data regarding the activity of ceramide synthesis and turnover in vivo. Herein, we demonstrate the ability to measure ceramide kinetics by coupling the administration of [2 H]water with LC-MS/MS analyses...
March 6, 2018: American Journal of Physiology. Endocrinology and Metabolism
Eugenia Morselli, Roberta de Souza Santos, Su Gao, Yenniffer Ávalos, Alfredo Criollo, Biff F Palmer, Deborah J Clegg
Estrogens and their receptors play key roles in regulating body weight, energy expenditure, and metabolic homeostasis. It is known that lack of estrogens promotes increased food intake and induces the expansion of adipose tissues, for which much is known. An area of estrogenic research that has received less attention is the role of estrogens and their receptors in influencing intermediary lipid metabolism in organs such as the brain. In this review, we highlight the actions of estrogens and their receptors in regulating their impact on modulating fatty acid content, utilization, and oxidation through their direct impact on intracellular signaling cascades within the central nervous system...
March 6, 2018: American Journal of Physiology. Endocrinology and Metabolism
Frank T Spradley, Jillian A Smith, Barbara T Alexander, Christopher D Anderson
Intrauterine growth restriction (IUGR) is linked to increased risk for chronic disease. Placental ischemia and insufficiency in the mother are implicated in predisposing IUGR offspring to metabolic dysfunction, including hypertension, insulin resistance, abnormalities in glucose homeostasis, and non-alcoholic fatty liver disease (NAFLD). Whether these metabolic disturbances contribute to the developmental origins of exaggerated cardiovascular-renal disease (CVRD) risk accompanying IUGR is unclear. IUGR impacts the pancreas, adipose tissue, and liver, which are hypothesized to program for hepatic insulin resistance and subsequent NAFLD...
March 6, 2018: American Journal of Physiology. Endocrinology and Metabolism
Javier R Jaldin-Fincati, Rafaela V S Pereira, Philip J Bilan, Amira Klip
Whereas the blood microvasculature constitutes a biological barrier to the action of blood-borne insulin on target tissues, the lymphatic microvasculature might act as a barrier to subcutaneously administrated insulin reaching the circulation. Here, we evaluate the interaction of insulin with primary microvascular endothelial cells of lymphatic (HDLEC) and blood (HAMEC) origin, derived from human dermal and adipose tissues, respectively. HDLEC express higher levels of insulin receptor (IR) and signal in response to insulin as low as 2...
March 6, 2018: American Journal of Physiology. Endocrinology and Metabolism
Isaac Asare-Bediako, Rebecca L Paszkiewicz, Stella P Kim, Orison O Woolcott, Cathryn M Kolka, Miguel Burch, Morvarid Kabir, Francesca Piccinini, Richard N Bergman
Hyperinsulinemia, accompanied by reduced first-pass hepatic insulin extraction (FPE) and increased secretion, is a primary response to insulin resistance. Different in vivo methods are used to estimate the clearance of insulin, which is assumed to reflect FPE. We compared two methodologically different but commonly used indirect estimates with directly measured FPE in healthy dogs (n = 9). The indirect methods were; 1) metabolic clearance rate of insulin (MCR) during the hyperinsulinemic euglycemic clamp (EGC), a steady state method, and 2) fractional clearance rate of insulin (FCR) during the frequently sampled intravenous glucose tolerance test (FSIGT), a dynamic method...
March 6, 2018: American Journal of Physiology. Endocrinology and Metabolism
Erika M Ripley, Geoffrey D Clarke, Vala Hamidi, Robert A Martinez, Floyd D Settles, Carolina Solis, Shengwen Deng, Muhammad Abdul-Ghani, Devjit Tripathy, Ralph A DeFronzo
Mitochondrial dysfunction has been described in insulin resistant (IR) states including type 2 diabetes mellitus (T2DM). Previous studies using31 P-MRS in T2DM reported results as relative concentrations of metabolite ratios, which could obscure changes in phosphocreatine [PCr] and [ATP] and attenuate differences between T2DM and NGT individuals. We used a novel image-guided31 P-MRS method to quantitate phosphorus metabolites in vastus lateralis (VL) muscle in 11 T2DM and 14 NGT subjects. Subjects received OGTT, euglycemic insulin clamp,31 P-MRS study to measure absolute concentrations (mM) of [PCr], inorganic phosphate [Pi], and [ATP], and VL muscle biopsy to evaluate mitochondrial density...
March 6, 2018: American Journal of Physiology. Endocrinology and Metabolism
Valentina Caracciolo, Jeanette Young, Donna Gonzales, Yinchun Ni, Stephen J Flowers, Ross Summer, Scott A Waldman, Jason K Kim, Dae Young Jung, Hye Lim Noh, Taekyoon Kim, Perry J Blackshear, Danielle O'Connell, Robert C Bauer, Caleb B Kallen
Obesity is associated with adipose tissue inflammation that contributes to insulin resistance. Zinc Finger Protein 36 (Zfp36) is an mRNA-binding protein that reduces inflammation by binding to cytokine transcripts and promoting their degradation. We hypothesized that myeloid-specific deficiency of Zfp36 would lead to increased adipose tissue inflammation and reduced insulin sensitivity in diet-induced obese mice. As expected, wild type (Control) mice became obese and diabetic on a high-fat diet and obese mice with myeloid-specific loss of Zfp36 (KO) demonstrated increased adipose tissue and liver cytokine mRNA expression compared to Control mice...
March 6, 2018: American Journal of Physiology. Endocrinology and Metabolism
Candace M Reno, Allie Skinner, Justin Bayles, Y Stefanie Chen, Dorit Daphna-Iken, Simon J Fisher
We previously demonstrated that insulin induced severe hypoglycemia associated sudden death is largely mediated by fatal cardiac arrhythmias. In the current study, a pharmacological approach was taken to explore the potential contribution of hypoglycemic seizures and the sympathoadrenergic system in mediating severe hypoglycemia associated sudden death. Adult Sprague Dawley rats were randomized into one of four treatment groups: 1) saline (SAL), 2) anti-arrhythmic (β1 blocker atenolol), 3) anti-seizure (Levetiracetam), and 4) combination anti-arrhythmic+anti-seizure (β1 blocker+Levetiracetam)...
February 27, 2018: American Journal of Physiology. Endocrinology and Metabolism
Alexis Bretin, Andrew T Gewirtz, Benoit Chassaing
The concept that the gut microbiota plays a broadly important role in health and disease in general, and metabolic health in particular, is now well established. Yet, many of the underlying mechanisms remain poorly understood, while approaches to reliably manipulate the microbiota to promote health have not yet been clearly defined. Nonetheless, progresses in these areas are steadily accelerating. Herein, we review select areas of progress that have been made in the last year that should hasten the era in which the microbiota can be therapeutically manipulated to promote metabolic health...
February 27, 2018: American Journal of Physiology. Endocrinology and Metabolism
Dionysios V Chartoumpekis, Dushani L Palliyaguru, Nobunao Wakabayashi, Marco Fazzari, Nicholas Kh Khoo, Francisco J Schopfer, Ian Sipula, Yoko Yagishita, George K Michalopoulos, Robert M O'Doherty, Thomas W Kensler
Nrf2 is a canonical regulator of cytoprotective gene expression but evidence of its crosstalk with other pathways, including metabolic ones, is ever increasing. Pharmacologic or systemic genetic activation of the Nrf2 pathway partially protects from obesity in mice and ameliorates fasting hyperglycemia in mice and humans. However, systemic Nrf2 deletion also protected from diet-induced obesity and insulin resistance in mice. To further investigate the effect of the disruption of Nrf2 on obesity in a tissue-specific manner, we focused on adipocytes and hepatocytes with targeted deletion of Nrf2...
February 27, 2018: American Journal of Physiology. Endocrinology and Metabolism
Luca Meoli, Nitin K Gupta, Nima Saeidi, Courtney Panciotti, Sudha B Biddinger, Kathleen E Corey, Nicholas Stylopoulos
Treatment of non-alcoholic fatty liver disease (NAFLD) focuses on the underlying metabolic syndrome, and Roux-en-Y gastric bypass surgery (RYGB) remains one of the most effective options. In rodents and human patients, RYGB induces an increase in the gene and protein expression levels of the M2 isoenzyme of Pyruvate Kinase (PKM2) in the jejunum. Since PKM2 can be secreted in the circulation, our hypothesis was that the circulating levels of PKM2 increase after RYGB. Our data, however, revealed an unexpected finding and a potential new role of PKM2 for the natural history of metabolic syndrome and NAFLD...
February 20, 2018: American Journal of Physiology. Endocrinology and Metabolism
Difei Wang, Huiying Cong, Xiaoli Wang, Yanli Cao, Shoichiro Ikuyama, Bin Fan, Jianqiu Gu
Pycnogenol (PYC), a combination of active flavonoids derived from French maritime pine bark, is a natural antioxidant that has various pharmacological activities. Here, we investigated the beneficial effect of PYC on diet-induced hepatic steatosis. Apolipoprotein E (ApoE)-deficient male mice were administered PYC at oral doses of 30 or 100 mg•kg-1 •day-1 for two weeks in advance and were then fed a high cholesterol and fat diet (HCD) for eight weeks. Biochemical, immunohistochemical, and gene expression analyses were conducted to explore the effect of PYC on lipid metabolism in ApoE-deficient mice on a HCD...
February 20, 2018: American Journal of Physiology. Endocrinology and Metabolism
Mariana Peduti Halah, Paula Beatriz Marangon, Jose Antunes-Rodrigues, Lucila L K Elias
Neonatal nutritional changes induce long-lasting effects on energy homeostasis. Adiponectin influences food intake and body weight. The aim of this study was to investigate the effects of neonatal nutritional programming on the central stimulation of adiponectin. Male Wistar rats were divided on postnatal (PN) day 3, in litters of 3 (small litter, SL), 10 (normal litter, NL), or 16 pups per dam (large litter, LL). We assessed body weight gain for 60 days, adiponectin concentration and white adipose tissue weight...
February 13, 2018: American Journal of Physiology. Endocrinology and Metabolism
Tanya J Little, Nada Cvijanovic, Nicholas V DiPatrizio, Donovan A Argueta, Christopher K Rayner, Christine Feinle-Bisset, Richard L Young
INTRODUCTION/AIMS: Intestinal production of endocannabinoid and oleoylethanolamide (OEA) is impaired in high-fat diet/obese rodents, leading to reduced satiety. Such diets also alter the intestinal microbiome in association with enhanced intestinal permeability and inflammation, however little is known of these effects in humans. This study aimed to: (i) evaluate effects of lipid on plasma anandamide (AEA), 2-arachidonyl-sn-glycerol (2-AG) and OEA in humans, and (ii) examine relationships with intestinal permeability, inflammation markers and incretin hormone secretion...
February 13, 2018: American Journal of Physiology. Endocrinology and Metabolism
Laura C Kutz, Shreya T Mukherji, Xiaoliang Wang, Amber Bryant, Isabel Larre, Judith A Heiny, Jerry B Lingrel, Sandrine V Pierre, Zijian Xie
The distribution of Na/K-ATPase α isoforms in skeletal muscle is unique, with α1 as the minor (15%) isoform and α2 comprising the bulk of the Na/K-ATPase pool. The acute and isoform-specific role of α2 in muscle performance and resistance to fatigue is well known, but the isoform-specific role of α1 has not been as thoroughly investigated. In vitro, we reported that α1 has a role in promoting cell growth that is not supported by α2. To assess whether α1 serves this isoform-specific trophic role in the skeletal muscle, we used the Na/K-ATPase α1 haploinsufficient (α1+/-) mice...
February 13, 2018: American Journal of Physiology. Endocrinology and Metabolism
Kohei Kido, Satoru Ato, Takumi Yokokawa, Koji Sato, Satoshi Fujita
Adapter protein containing PH domain, PTB domain, and leucine zipper motif 1 (APPL1) has been reported as a positive regulator of insulin-stimulated Akt activation. The expression of APPL1 is reduced in skeletal muscles of type 2 diabetic (T2D) animals, implying that APPL1 may be an important factor affecting insulin sensitivity. However, the regulation of APPL1 expression and the physiological interventions modulating these effects are unclear. Accordingly, we first confirmed that APPL1 expression and Akt phosphorylation were significantly attenuated in skeletal muscles of T2D rats...
February 6, 2018: American Journal of Physiology. Endocrinology and Metabolism
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