Jejunal administration of glucose enhances acyl ghrelin suppression in obese humans
Ghrelin is a gastric hormone that stimulates hunger and worsens glucose metabolism. Circulating ghrelin is decreased after Roux-en-Y gastric bypass (RYGB) surgery; however, the mechanism(s) underlying this change is unknown. We tested the hypothesis that jejunal nutrient exposure plays a significant role in ghrelin suppression after RYGB. Feeding tubes were placed in the stomach or jejunum in 13 obese subjects to simulate pre-RYGB or post-RYGB glucose exposure to the gastrointestinal (GI) tract, respectively, without the confounding effects of caloric restriction, weight loss, and surgical stress. On separate study days, t...
Source: AJP: Endocrinology and Metabolism - July 4, 2016 Category: Endocrinology Authors: Tamboli, R. A., Sidani, R. M., Garcia, A. E., Antoun, J., Isbell, J. M., Albaugh, V. L., Abumrad, N. N. Tags: Articles Source Type: research
Intake of branched-chain or essential amino acids attenuates the elevation in muscle levels of PGC-1{alpha}4 mRNA caused by resistance exercise
In conclusion, induction of PGC-1α4 does not appear to regulate the nutritional (BCAA or EAA)-mediated activation of mTORC1 in human muscle. (Source: AJP: Endocrinology and Metabolism)
Source: AJP: Endocrinology and Metabolism - July 4, 2016 Category: Endocrinology Authors: Samuelsson, H., Moberg, M., Apro, W., Ekblom, B., Blomstrand, E. Tags: Articles Source Type: research
The effects of paternal high-fat diet exposure on offspring metabolism with epigenetic changes in the mouse adiponectin and leptin gene promoters
Recent studies have demonstrated that epigenetic changes resulting from malnutrition might play important roles in transgenerational links with metabolic diseases. Previously, we observed that exposure to a high-fat diet (HFD) in utero caused a metabolic syndrome-like phenomenon through epigenetic modifications of the adiponectin and leptin genes that persisted for multiple generations. Recent etiological studies indicated that paternal BMI had effects on offspring BMI that were independent of but additive to maternal BMI effects. Thus, we examined whether paternal HFD-induced obesity affected the metabolic status of offsp...
Source: AJP: Endocrinology and Metabolism - July 4, 2016 Category: Endocrinology Authors: Masuyama, H., Mitsui, T., Eguchi, T., Tamada, S., Hiramatsu, Y. Tags: Articles Source Type: research
Differential regulation of lipid and protein metabolism in obese vs. lean subjects before and after a 72-h fast
Increased availability of lipids may conserve muscle protein during catabolic stress. Our study was designed to define 1) intracellular mechanisms leading to increased lipolysis and 2) whether this scenario is associated with decreased amino acid and urea fluxes, and decreased muscle amino acid release in obese subjects under basal and fasting conditions. We therefore studied nine lean and nine obese subjects twice, after 12 and 72 h of fasting, using measurements of mRNA and protein expression and phosphorylation of lipolytic and protein metabolic signaling molecules in fat and muscle together with whole body and forearm ...
Source: AJP: Endocrinology and Metabolism - July 4, 2016 Category: Endocrinology Authors: Bak, A. M., Moller, A. B., Vendelbo, M. H., Nielsen, T. S., Viggers, R., Rungby, J., Pedersen, S. B., Jorgensen, J. O. L., Jessen, N., Moller, N. Tags: Articles Source Type: research
Hepcidin and 1,25(OH)2D3 effectively restore Ca2+ transport in {beta}-thalassemic mice: reciprocal phenomenon of Fe2+ and Ca2+ absorption
In conclusion, both 1,25(OH)2D3 and hepcidin could be used to alleviate the β-thalassemia-associated impairment of calcium absorption. Therefore, our study has shed light on the development of a treatment strategy to rescue calcium dysregulation in β-thalassemia. (Source: AJP: Endocrinology and Metabolism)
Source: AJP: Endocrinology and Metabolism - July 4, 2016 Category: Endocrinology Authors: Kraidith, K., Svasti, S., Teerapornpuntakit, J., Vadolas, J., Chaimana, R., Lapmanee, S., Suntornsaratoon, P., Krishnamra, N., Fucharoen, S., Charoenphandhu, N. Tags: Articles Source Type: research
No insulating effect of obesity
We examined a series of obesity models [mice fed high-fat diets and kept at different temperatures, classical diet-induced obese mice, ob/ob mice, and obesity-prone (C57BL/6) vs. obesity-resistant (129S) mice]. We found that neither acclimation temperature nor any kind or degree of obesity affected the thermal insulation of the mice when analyzed at the whole mouse level or as energy expenditure per lean weight. Calculation per body weight erroneously implied increased insulation in obese mice. We conclude that, in contrast to what would be expected, obesity of any kind does not increase thermal insulation in mice, and the...
Source: AJP: Endocrinology and Metabolism - July 4, 2016 Category: Endocrinology Authors: Fischer, A. W., Csikasz, R. I., von Essen, G., Cannon, B., Nedergaard, J. Tags: Articles Source Type: research
{beta}-Cell deletion of Nr4a1 and Nr4a3 nuclear receptors impedes mitochondrial respiration and insulin secretion
In this study, we examined whether Nr4a expression impacts pancreatic β-cell mitochondrial function. Here, we show that β-cell mitochondrial respiration is dependent on the nuclear receptors Nr4a1 and Nr4a3. Mitochondrial respiration in permeabilized cells was significantly decreased in β-cells lacking Nr4a1 or Nr4a3. Furthermore, respiration rates of intact cells deficient for Nr4a1 or Nr4a3 in the presence of 16 mM glucose resulted in decreased glucose mediated oxygen consumption. Consistent with this reduction in respiration, a significant decrease in glucose-stimulated insulin secretion rates is observed...
Source: AJP: Endocrinology and Metabolism - July 4, 2016 Category: Endocrinology Authors: Reynolds, M. S., Hancock, C. R., Ray, J. D., Kener, K. B., Draney, C., Garland, K., Hardman, J., Bikman, B. T., Tessem, J. S. Tags: Call for Papers - Islet Biology Source Type: research
MiR-206 is expressed in pancreatic islets and regulates glucokinase activity
In this study, we investigated the role of miR-206 as a posttranscriptional regulator of Gck. In addition, we examined the effects of miR-206 on glucose tolerance, GSIS, and gene expression in control and germ line miR-206 knockout (KO) mice fed either with chow or high-fat diet (HFD). MiR-206 was found in Gck-expressing tissues and was differentially altered in response to HFD feeding. Pancreatic islets showed the most profound induction in the expression of miR-206 in response to HFD. Chow- and HFD-fed miR-206KO mice have improved glucose tolerance and GSIS but unaltered insulin sensitivity. In silico analysis of Gck mRN...
Source: AJP: Endocrinology and Metabolism - July 4, 2016 Category: Endocrinology Authors: Vinod, M., Patankar, J. V., Sachdev, V., Frank, S., Graier, W. F., Kratky, D., Kostner, G. M. Tags: Call for Papers - Islet Biology Source Type: research
Emerging role for regulated in development and DNA damage 1 (REDD1) in the regulation of skeletal muscle metabolism
Since its discovery, the protein regulated in development and DNA damage 1 (REDD1) has been implicated in the cellular response to various stressors. Most notably, its role as a repressor of signaling through the central metabolic regulator, the mechanistic target of rapamycin in complex 1 (mTORC1) has gained considerable attention. Not surprisingly, changes in REDD1 mRNA and protein have been observed in skeletal muscle under various physiological conditions (e.g., nutrient consumption and resistance exercise) and pathological conditions (e.g., sepsis, alcoholism, diabetes, obesity) suggesting a role for REDD1 in regulati...
Source: AJP: Endocrinology and Metabolism - July 4, 2016 Category: Endocrinology Authors: Gordon, B. S., Steiner, J. L., Williamson, D. L., Lang, C. H., Kimball, S. R. Tags: Reviews Source Type: research
Age-related impairments in skeletal muscle PDH phosphorylation and plasma lactate are indicative of metabolic inflexibility and the effects of exercise training
The purpose of this study was to determine whether plasma lactate and skeletal muscle glucose regulatory pathways, specifically PDH dephosphorylation, are impaired during hyperinsulinemic conditions in middle- to older-aged individuals and determine whether exercise training could improve key variables responsible for skeletal muscle PDH regulation. Eighteen young (19–29 yr; n = 9 males and 9 females) and 20 middle- to older-aged (57–82 yr; n = 10 males and 10 females) individuals underwent a 2-h euglycemic hyperinsulinemic clamp. Plasma samples were obtained at baseline and at 30, 50, 90, and 120 min for analy...
Source: AJP: Endocrinology and Metabolism - June 30, 2016 Category: Endocrinology Authors: Consitt, L. A., Saxena, G., Saneda, A., Houmard, J. A. Tags: Articles Source Type: research
Liver-derived IGF-I regulates cortical bone mass but is dispensable for the osteogenic response to mechanical loading in female mice
In conclusion, liver-derived IGF-I regulates cortical bone mass, cortical porosity, and mechanical strength under normal (nonloaded) conditions. However, despite an ~70% reduction in circulating IGF-I, the osteogenic response to mechanical loading was not attenuated in the LI-IGF-I–/– mice. (Source: AJP: Endocrinology and Metabolism)
Source: AJP: Endocrinology and Metabolism - June 30, 2016 Category: Endocrinology Authors: Svensson, J., Windahl, S. H., Saxon, L., Sjögren, K., Koskela, A., Tuukkanen, J., Ohlsson, C. Tags: Articles Source Type: research
Perilipin 5 is dispensable for normal substrate metabolism and in the adaptation of skeletal muscle to exercise training
Cytoplasmic lipid droplets provide a reservoir for triglyceride storage and are a central hub for fatty acid trafficking in cells. The protein perilipin 5 (PLIN5) is highly expressed in oxidative tissues such as skeletal muscle and regulates lipid metabolism by coordinating the trafficking and the reversible interactions of effector proteins at the lipid droplet. PLIN5 may also regulate mitochondrial function, although this remains unsubstantiated. Hence, the aims of this study were to examine the role of PLIN5 in the regulation of skeletal muscle substrate metabolism during acute exercise and to determine whether PLIN5 is...
Source: AJP: Endocrinology and Metabolism - June 30, 2016 Category: Endocrinology Authors: Mohktar, R. A. M., Montgomery, M. K., Murphy, R. M., Watt, M. J. Tags: Articles Source Type: research
Lack of mitochondria-generated acetyl-CoA by pyruvate dehydrogenase complex downregulates gene expression in the hepatic de novo lipogenic pathway
During the absorptive state, the liver stores excess glucose as glycogen and synthesizes fatty acids for triglyceride synthesis for export as very low density lipoproteins. For de novo synthesis of fatty acids from glucose, the mitochondrial pyruvate dehydrogenase complex (PDC) is the gatekeeper for the generation of acetyl-CoA from glucose-derived pyruvate. Here, we tested the hypothesis that limiting the supply of PDC-generated acetyl-CoA from glucose would have an impact on expression of key genes in the lipogenic pathway. In the present study, although the postnatal growth of liver-specific PDC-deficient (L-PDCKO) male...
Source: AJP: Endocrinology and Metabolism - June 30, 2016 Category: Endocrinology Authors: Mahmood, S., Birkaya, B., Rideout, T. C., Patel, M. S. Tags: Articles Source Type: research
Reduced intestinal lipid absorption and body weight-independent improvements in insulin sensitivity in high-fat diet-fed Park2 knockout mice
Mitochondrial dysfunction is associated with many human diseases and results from mismatch of damage and repair over the life of the organelle. PARK2 is a ubiquitin E3 ligase that regulates mitophagy, a repair mechanism that selectively degrades damaged mitochondria. Deletion of PARK2 in multiple in vivo models results in susceptibility to stress-induced mitochondrial and cellular dysfunction. Surprisingly, Park2 knockout (KO) mice are protected from nutritional stress and do not develop obesity, hepatic steatosis or insulin resistance when fed a high-fat diet (HFD). However, these phenomena are casually related and the ph...
Source: AJP: Endocrinology and Metabolism - June 30, 2016 Category: Endocrinology Authors: Costa, D. K., Huckestein, B. R., Edmunds, L. R., Petersen, M. C., Nasiri, A., Butrico, G. M., Abulizi, A., Harmon, D. B., Lu, C., Mantell, B. S., Hartman, D. J., Camporez, J.-P. G., O'Doherty, R. M., Cline, G. W., Shulman, G. I., Jurczak, M. J. Tags: Articles Source Type: research
Characterizing active and inactive brown adipose tissue in adult humans using PET-CT and MR imaging
Activated brown adipose tissue (BAT) plays an important role in thermogenesis and whole body metabolism in mammals. Positron emission tomography (PET)-computed tomography (CT) imaging has identified depots of BAT in adult humans, igniting scientific interest. The purpose of this study is to characterize both active and inactive supraclavicular BAT in adults and compare the values to those of subcutaneous white adipose tissue (WAT). We obtained [18F]fluorodeoxyglucose ([18F]FDG) PET-CT and magnetic resonance imaging (MRI) scans of 25 healthy adults. Unlike [18F]FDG PET, which can detect only active BAT, MRI is capable of de...
Source: AJP: Endocrinology and Metabolism - June 30, 2016 Category: Endocrinology Authors: Gifford, A., Towse, T. F., Walker, R. C., Avison, M. J., Welch, E. B. Tags: Articles Source Type: research
