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How Do Adipocytes Respond To Insulin

Adipose Tissue Hypoxia: Effects On Metabolism And Insulin Sensitivity

Adipose Tissue Hypoxia: Effects On Metabolism And Insulin Sensitivity

Received date: February 27, 2016 Accepted date: March 01, 2016 Published date: March 10, 2016 Citation:Lounsbury EA, Zhao FQ, Lounsbury KM (2016) Adipose Tissue Hypoxia: Effects on Metabolism and Insulin Sensitivity. J Nutr Food Sci 6:488. doi: 10.4172/2155-9600.1000488 Copyright: 2016 Lounsbury EA, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Obesity is associated with an increased risk of insulin resistance and type 2 diabetes . These risks have been correlated with a chronic inflammatory response of the adipose tissue that affects glucose and lipid metabolism. Hypoxia, stemming from inadequate adipose tissue blood flow in obesity, has been shown to be an important contributor to this inflammatory response. The response to hypoxia includes changes in gene expression that affect glucose uptake, glycolysis, lipid metabolism , inflammation, and angiogenesis. This review describes the effects of obesity on chronic and intermittent hypoxia in white adipose tissue and highlights the resulting effects on gene expression and cell metabolism that can affect the onset of systemic insulin resistance and the development of chronic metabolic dysfunction in type 2 diabetes. Obesity ; Glycolysis ; Metabolism; Hypoxia ; Insulin Adipose tissue is known to be an important endocrine organ that communicates metabolic information to the brain and other tissues. Peripheral insulin resistance and inflammation are evolutionarily conserved responses to preserve glucose supply and eliminate harmful stimuli during localized or systemic stress events. It is becoming increasingly clear that the connect Continue reading >>

Distinct Changes In Adipose Tissue And Muscle In Response To Excess Systemic Glucose In Rats

Distinct Changes In Adipose Tissue And Muscle In Response To Excess Systemic Glucose In Rats

Research Article,Endocrinol Diabetes Res Vol: 1 Issue: 2 Distinct Changes in Adipose Tissue and Muscle in Response to Excess Systemic Glucose in Rats X Julia Xu 1 * , Amanda E Brandon 2 , Ella Stuart 2 , Kaajal Patel 1 , Reyhan Gedik 1 , Asish Saha 1 , Edward W Kraegen 2 , 3 and Neil B Ruderman 1 1 Department of Medicine, Diabetes and Metabolism Unit, Section of Endocrinology, Boston University Medical Center, USA 2 Diabetes and Obesity Program, Garvan Institute of Medical Research, Australia, UK 3 Faculty of Medicine, University of New South Wales, Sydney, Australia, UK Department of Medicine, Diabetes and Metabolism Unit, Section of Endocrinology, Boston University Medical Center, 650 Albany Street, MA 02118, Boston, USA Received: November 26, 2014 Accepted: April 29, 2015 Published: May 01, 2015 Citation: Xu XJ, Brandon AE, Stuart E, Patel K, Gedik R, et al. (2015) Distinct Changes in Adipose Tissue and Muscle in Response to Excess Systemic Glucose in Rats. Endocrinol Diabetes Res 1:2. doi:10.4172/2470-7570.1000106 Objective: Excess nutrients can cause insulin resistance in skeletal muscle in vivo. However, the response of white adipose tissue is less clear. In a chronic glucose infusion model (1 and 4 days), distinct adaptations in muscle and white adipose tissue have been described. Muscle developed sustained insulin resistance after 1 day of glucose infusion but adipose tissue did not. Exactly what distinguishes adipose tissue from muscle in response to glucose oversupply remains to be determined. The aim of the present study was to investigate the early (3-8 h) metabolic and signaling changes that take place in epididymal fat pads, and to a lesser extent, red quadriceps muscle, using an acute glucose infusion model. Methods: Hyperglycemia (~11 mM) and hyperinsul Continue reading >>

Resveratrol Reduces The Inflammatory Response In Adipose Tissue And Improves Adipose Insulin Signaling In High-fat Diet-fed Mice

Resveratrol Reduces The Inflammatory Response In Adipose Tissue And Improves Adipose Insulin Signaling In High-fat Diet-fed Mice

This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited. Ding S, Jiang J, Wang Z, Zhang G, Yin J, Wang X, Wang S, Yu Z. (2018) Resveratrol reduces the inflammatory response in adipose tissue and improves adipose insulin signaling in high-fat diet-fed mice. PeerJ 6:e5173 Obesity-induced glucose metabolism disorder is associated with chronic, low-grade, systemic inflammation and is considered a risk factor for diabetes and metabolic syndrome. Resveratrol (RES), a natural anti-inflammatory compound, is observed to improve glucose tolerance and insulin sensitivity in obese rodents and humans. This study aimed to test the effects of RES administration on insulin signaling and the inflammatory response in visceral white adipose tissue (WAT) caused by a high-fat diet (HFD) in mice. A total of 40 wild-type C57BL/6 male mice were divided into four groups (10 in each group): the standard chow diet (STD) group was fed a STD; the HFD group was fed a HFD; and the HFD-RES/L and HFD-RES/H groups were fed a HFD plus RES (200 and 400 mg/kg/day, respectively). The L and H in RES/L and RES/H stand for low and high, respectively. Glucose tolerance, insulin sensitivity, circulating inflammatory biomarkers and lipid profile were determined. Quantitative PCR and Western blot were used to determine the expression of CC-chemokine receptor 2 (CCR2), other inflammation markers, glucose transporter 4 (GLUT4), insulin receptor substrate 1 (IRS-1) and pAkt/Akt and to assess target Continue reading >>

Jci -insulin Resistance Causes Inflammation In Adipose Tissue

Jci -insulin Resistance Causes Inflammation In Adipose Tissue

Research Article Inflammation Metabolism Free access | 10.1172/JCI96139 Insulin resistance causes inflammation in adipose tissue 1Biozentrum, University of Basel, Basel, Switzerland. 3Department of Surgery, St. Claraspital, Basel, Switzerland. Address correspondence to: Mitsugu Shimobayashi or Michael N. Hall, Klingelbergstrasse 50/70, Basel 4056, Switzerland. Phone: 41.61.207.2171; Email: [email protected] (MS). Phone: 41.61.207.2150; Email: [email protected] (MNH). Find articles by Shimobayashi, M. in: JCI | PubMed | Google Scholar 1Biozentrum, University of Basel, Basel, Switzerland. 3Department of Surgery, St. Claraspital, Basel, Switzerland. Address correspondence to: Mitsugu Shimobayashi or Michael N. Hall, Klingelbergstrasse 50/70, Basel 4056, Switzerland. Phone: 41.61.207.2171; Email: [email protected] (MS). Phone: 41.61.207.2150; Email: [email protected] (MNH). Find articles by Albert, V. in: JCI | PubMed | Google Scholar 1Biozentrum, University of Basel, Basel, Switzerland. 3Department of Surgery, St. Claraspital, Basel, Switzerland. Address correspondence to: Mitsugu Shimobayashi or Michael N. Hall, Klingelbergstrasse 50/70, Basel 4056, Switzerland. Phone: 41.61.207.2171; Email: [email protected] (MS). Phone: 41.61.207.2150; Email: [email protected] (MNH). Find articles by Woelnerhanssen, B. in: JCI | PubMed | Google Scholar 1Biozentrum, University of Basel, Basel, Switzerland. 3Department of Surgery, St. Claraspital, Basel, Switzerland. Address correspondence to: Mitsugu Shimobayashi or Michael N. Hall, Klingelbergstrasse 50/70, Basel 4056, Switzerland. Phone: 41.61.207.2171; Email: [email protected] (MS). Phone: 41.61.207.2150; Email: [email protected] (MNH). Find articles by Frei, I. in: JCI | PubMed | Googl Continue reading >>

Adipose Tissue And Adipocyte Dysregulation - Em|consulte

Adipose Tissue And Adipocyte Dysregulation - Em|consulte

Received:19August2013; accepted:25August2013 Adipose tissue and adipocyte dysregulation aINSERM/UPS UMR 1048-I2MR, Institut des Maladies Mtaboliques et Cardiovasculaires, Hpital Rangueil, BP 84225, 31432 Toulouse cedex, France bUniversit Paul-Sabatier, 118, route de Narbonne, 31062 Toulouse cedex 9, France INSERM/UPS UMR 1048-I2MR, Institut des Maladies Mtaboliques et Cardiovasculaires, Hpital Rangueil, BP 84225, 31432 Toulouse cedex, France. Tel.: +33 5 61 32 56 41. Obesity-associated insulin resistance is a complex disorder involving a number of candidate molecules, pathways and transduction systems possessing potential causal actions. Inflammation in adipose tissue (AT) is one mechanism proposed to explain the development of insulin resistance, while identification of factors that lead to or cause AT dysfunction when it reaches its limit of expansion represents an important challenge. Pathological expansion of AT is characterized by changes in its blood flow, and the presence of enlarged and dysfunctional adipocytes that begin an inflammatory campaign of altered adipokine and cytokine secretions. Adipocyte senescence, necrosis and death are associated with increased immune cell and macrophage infiltration of AT in obesity. This can boost inflammation and reinforce fat cell dysfunction and death. In addition, pathological fat mass expansion is also related to limited recruitment of fat cell progenitors able to proliferate and differentiate into healthy small fat cells to compensate for cell death and preserve adipocyte numbers. Limiting vascular development and enhancing fibrotic processes worsen inflammation towards chronic irreversibility. The AT expandability hypothesis states that failure of AT expansion is one of the key factors linking positive energy balance a Continue reading >>

3t3-l1 Adipocytes As A Cell Culture Model Of Insulin Resistance

3t3-l1 Adipocytes As A Cell Culture Model Of Insulin Resistance

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Ck2 Modulates Adipocyte Insulin-signaling And Is Up-regulated In Human Obesity

Ck2 Modulates Adipocyte Insulin-signaling And Is Up-regulated In Human Obesity

CK2 modulates adipocyte insulin-signaling and is up-regulated in human obesity Scientific Reportsvolume7, Articlenumber:17569 (2017) | Download Citation Insulin plays a major role in glucose metabolism and insulin-signaling defects are present in obesity and diabetes. CK2 is a pleiotropic protein kinase implicated in fundamental cellular pathways and abnormally elevated in tumors. Here we report that in human and murine adipocytes CK2-inhibition decreases the insulin-induced glucose-uptake by counteracting Akt-signaling and GLUT4-translocation to the plasma membrane. In mice CK2 acts on insulin-signaling in adipose tissue, liver and skeletal muscle and its acute inhibition impairs glucose tolerance. Notably, CK2 protein-level and activity are greatly up-regulated in white adipose tissue from ob/ob and db/db mice as well as from obese patients, regardless the severity of their insulin-resistance and the presence of pre-diabetes or overt type 2 diabetes. Weight loss obtained by both bariatric surgery or hypocaloric diet reverts CK2 hyper-activation to normal level. Our data suggest a central role of CK2 in insulin-sensitivity, glucose homeostasis and adipose tissue remodeling. CK2 up-regulation is identified as a hallmark of adipose tissue pathological expansion, suggesting a new potential therapeutic target for human obesity. Insulin plays a major role in glucose metabolism increasing its utilization mostly by adipose tissue (AT) and skeletal muscle, and inhibiting hepatic gluconeogenesis. It promotes tissue glucose uptake through the regulated trafficking of endosomal sorting vesicles containing glucose transporter 4 (GLUT4) (GSVs) 1 , 2 . Insulin also acts as an essential growth factor for AT formation via recruitment and adipogenic differentiation of specific precurs Continue reading >>

Adipose Tissue

Adipose Tissue

From Lipid Storage Compartment to Endocrine Organ Abstract Adipose tissue, when carried around in excessive amounts, predisposes to a large number of diseases. Epidemiological data show that the prevalence of obesity has significantly increased over the past 20 years and continues to do so at an alarming rate. Here, some molecular aspects of the key constituent of adipose tissue, the adipocyte, are reviewed. While the adipocyte has been studied for many years and remarkable insights have been gained about some processes, many areas of the physiology of the fat cell remain unexplored. Our understanding of how cellular events in the adipocyte affect the local environment through paracrine interactions and how systemic effects are achieved through endocrine interactions is rudimentary. While storage and release of lipids are major functions of adipocytes, the adipocyte also uses specific lipid molecules for intracellular signaling and uses a host of protein factors to communicate with essentially every organ system in the body. The intensity and complexity of these signals are highly regulated, differ in each fat pad, and are dramatically affected by various disease states. We have appreciated for a long time that excess adipose tissue predisposes toward the development of insulin resistance. It is less well known, but equally important, that loss of selective fat pads (or absence of adipose tissue altogether) is also associated with severe forms of insulin resistance (1–3). This is in part due to the absence of the compartment that is specialized for the storage of lipids under normal conditions. This leads to a dysregulation of triglyceride and free fatty acid levels, as well as a dysregulation of specific adipocyte-derived secretory proteins, a group of proteins that Continue reading >>

Acute In Vivo Effects Of Insulin On Gene Expression In Adipose Tissue In Insulin-resistant And Insulin-sensitive Subjects

Acute In Vivo Effects Of Insulin On Gene Expression In Adipose Tissue In Insulin-resistant And Insulin-sensitive Subjects

, Volume 49, Issue1 , pp 132140 | Cite as Acute in vivo effects of insulin on gene expression in adipose tissue in insulin-resistant and insulin-sensitive subjects We determined the response of selected genes to in vivo insulin in adipose tissue in 21 non-diabetic women. The women were divided into insulin-sensitive and -resistant groups based on their median whole-body insulin sensitivity (8.70.4 vs 4.20.3mg kg1min1 for insulin-sensitive vs -resistant group). Subcutaneous adipose tissue biopsies were obtained before and after 3 and 6h of i.v. maintained euglycaemic hyperinsulinaemia. Adipose tissue mRNA concentrations of facilitated glucose transporter, member 1 (SLC2A1, previously known as GLUT1), facilitated glucose transporter, member 4 (SLC2A4, previously known as GLUT4), peroxisome proliferator-activated receptor ( PPARG), peroxisome proliferator-activated receptor co-activator 1 (PPARGC1A), 11-hydroxysteroid dehydrogenase-1 (HSD11B1), TNF, adiponectin (ADIPOQ), IL6 and the macrophage marker CD68 were measured using real-time PCR. Basal expression of insulin-sensitivity genes SLC2A4 and ADIPOQ was lower while that of insulin-resistance genes, HSD11B1 and IL6 was significantly higher in the insulin-resistant than in the insulin-sensitive group. Insulin significantly increased expression of insulin-sensitivity genes SLC2A4, PPARG, PPARGC1A and ADIPOQ in the insulin-sensitive group, while only expression of PPARG and PPARGC1A was increased in the insulin-resistant group. The expression of insulin-resistance genes HSD11B1 and IL6 was increased by insulin in the insulin-resistant group, but insulin failed to increase HSD11B1 expression in the insulin-sensitive group. At 6h, expression of HSD11B1, TNF and IL6 was significantly higher in the insulin-resistant than in th Continue reading >>

Myhealthywaist.org - Glucose/insulin Homeostasis

Myhealthywaist.org - Glucose/insulin Homeostasis

Glucose is abundant in a wide range of foods. In the fasted state, the liver provides the bulk of glucose to the bloodstream through glycogenolysis and gluconeogenesis. Insulin optimizes glucose uptake by skeletal muscle, its major peripheral user. Insulin also reduces liver glucose production after a meal and reduces fatty acid release by adipose tissue. These three major functions are important for glucose homeostasis. Expansion of intra-abdominal (visceral) fat causes adipocyte hypertrophy. This process triggers macrophages that, together with the enlarged adipocytes, locally secrete insulin-resistance-promoting molecules. Hypertrophied insulin-resistant intra-abdominal adipocytes release more fatty acids and proinflammatory adipokines into the bloodstream. The portal circulation carries these to the liver where they promote steatosis, insulin resistance, and local inflammation. The systemic circulation carries fatty acids and proinflammatory molecules to skeletal muscle where they promote lipid accumulation, insulin resistance, and local inflammation. Insulin resistance also affects the function of other systems and organs, including endothelial cells and cells of the vascular wall. This further increases CVD risk. Insulin resistance is believed to play a role in the development of many metabolic abnormalities that define the metabolic syndrome. It is also believed to be a strong link between intra-abdominal obesity and increased risk of type 2 diabetes and CVD. Targeting the fundamental cause of obesity-related insulin resistance by reducing intra-abdominal fat mass remains an important therapeutic objective. One of the most common metabolic complications of intra-abdominal (visceral) obesity is insulin resistance, a condition in which insulin no longer functions Continue reading >>

How Fat Cells Work

How Fat Cells Work

In the last section, we learned how fat in the body is broken down and rebuilt into chylomicrons, which enter the bloodstream by way of the lymphatic system. Chylomicrons do not last long in the bloodstream -- only about eight minutes -- because enzymes called lipoprotein lipases break the fats into fatty acids. Lipoprotein lipases are found in the walls of blood vessels in fat tissue, muscle tissue and heart muscle. Insulin When you eat a candy bar or a meal, the presence of glucose, amino acids or fatty acids in the intestine stimulates the pancreas to secrete a hormone called insulin. Insulin acts on many cells in your body, especially those in the liver, muscle and fat tissue. Insulin tells the cells to do the following: The activity of lipoprotein lipases depends upon the levels of insulin in the body. If insulin is high, then the lipases are highly active; if insulin is low, the lipases are inactive. The fatty acids are then absorbed from the blood into fat cells, muscle cells and liver cells. In these cells, under stimulation by insulin, fatty acids are made into fat molecules and stored as fat droplets. It is also possible for fat cells to take up glucose and amino acids, which have been absorbed into the bloodstream after a meal, and convert those into fat molecules. The conversion of carbohydrates or protein into fat is 10 times less efficient than simply storing fat in a fat cell, but the body can do it. If you have 100 extra calories in fat (about 11 grams) floating in your bloodstream, fat cells can store it using only 2.5 calories of energy. On the other hand, if you have 100 extra calories in glucose (about 25 grams) floating in your bloodstream, it takes 23 calories of energy to convert the glucose into fat and then store it. Given a choice, a fat cell w Continue reading >>

Insulin Modulates The Secretion Of Proteins From Mature 3t3-l1 Adipocytes: A Role For Transcriptional Regulation Of Processing

Insulin Modulates The Secretion Of Proteins From Mature 3t3-l1 Adipocytes: A Role For Transcriptional Regulation Of Processing

, Volume 49, Issue10 , pp 24532462 | Cite as Insulin modulates the secretion of proteins from mature 3T3-L1 adipocytes: a role for transcriptional regulation of processing Under conditions of insulin resistance and type 2 diabetes, fat cells are subjected to increased levels of insulin, which may have a major impact on the secretion of adipokines. Using transcriptomics and proteomics, we investigated how insulin affects the transcription and protein secretion profile of mature 3T3-L1 adipocytes. We found that insulin has a significant impact on protein secretion of 3T3-L1 adipocytes. However, transcription is not the major regulation point for these secreted proteins. For extracellular matrix components, our data suggest that the mRNA level of processing enzymes, but not of target proteins, is the regulating point at which insulin stimulates secretion and function of the relevant proteins. Among these enzymes, we report a novel finding, namely that sulfatase 2 gene is regulated by insulin, which may induce a functional change in cultured adipocytes. We propose that enhancement of protein processing and secretion rather than transcription of the secreted protein genes is part of the strategic role of insulin in the induction of cellular responses. AdipocytesInsulinProteomicsSecretionTranscriptomics matrix assisted laser desorption/ionisation-time of flight procollagen-proline, 2-oxoglutarate 4-dioxygenase (proline 4-hydroxylase), alpha 1 Supplementary material is available for this article at and is accessible for authorized users. Obesity is associated with insulin resistance and type 2 diabetes, implying that adipose tissue plays a role in the development of these disorders [ 1 ]. The primary function of adipose tissue is storage of fat, but it is also recognised as a Continue reading >>

Jci -the Role Of Adipose Cell Size And Adipose Tissue Insulin Sensitivity In The Carbohydrate Intolerance Of Human Obesity

Jci -the Role Of Adipose Cell Size And Adipose Tissue Insulin Sensitivity In The Carbohydrate Intolerance Of Human Obesity

The role of adipose cell size and adipose tissue insulin sensitivity in the carbohydrate intolerance of human obesity Find articles by Salans, L. in: JCI | PubMed | Google Scholar Find articles by Knittle, J. in: JCI | PubMed | Google Scholar Find articles by Hirsch, J. in: JCI | PubMed | Google Scholar First published January 1, 1968- More info Published in Volume 47, Issue 1 onJanuary 1, 1968 J Clin Invest.1968;47(1):153165. . Copyright 1968, The American Society for Clinical Investigation. First published January 1, 1968- Version history Glucose metabolism and insulin sensitivity of isolated human adipose tissue was studied as a function of adipose cell size and number. Glucose metabolism by these tissues was closely related to the number of cells in the fragment, irrespective of cell size. Adipose cells of obese individuals metabolized glucose to carbon dioxide and triglyceride at rates similar to adipose cells of nonobese subjects. In contrast, insulin responsiveness of adipose tissue was dependent upon adipose cell size. The larger its adipose cells the less insulin sensitive was the tissue. Thus, adipose tissue of obese subjects, with enlarged cells, showed a diminished response to insulin. After weight loss and reduction in adipose cell size, insulin sensitivity of the adipose tissue of obese patients was restored to normal. When adipose tissue of obese individuals showed impaired responsiveness to insulin, their plasma insulin levels, after oral glucose, were elevated. Weight loss and reduction in adipose cell size restored plasma insulin concentration to normal, concomitant with the return of normal tissue insulin sensitivity. Continue reading >>

White Adipocyte Vascular Endothelial Growth Factor: Regulation By Insulin

White Adipocyte Vascular Endothelial Growth Factor: Regulation By Insulin

White adipose tissue from rats was examined for insulin- responsive vascular endothelial growth factor 165 (VEGF) secretion and mRNA expression. When separated into it constituent fat vs. stromal-vascular cells using collagenase digestion methods, only the adipocytes (or whole fat tissue) responded to physiological insulin concentrations by doubling VEGF release over 4 and 24 h in culture. Adipocyte VEGF mRNA expression increased similarly. Several adipose depots were tested. Although omental fat cells had the highest rates of VEGF release, the differences were not significant. Insulin-stimulated VEGF release was mediated in part via PI3K, but not PKC. Additional hormones/agents were tested, including steroids, leptin, an adenosine analog, and norepinephrine. Only the latter compound increased VEGF production, and this effect was mediated by adenylate cyclase. Adjusting the incubation glucose concentration between 020 mm did not alter adipocyte VEGF release. An experimental mimic of hypoxia, CoCl2, also increased adipocyte VEGF, and this effect was additive with 100 nm insulin. These studies demonstrate that physiological insulin concentrations stimulate VEGF formation and expression in cultured rodent white adipocytes. Although the biological significance of this observation remains to be determined, if white adipocyte-derived VEGF has paracrine or systemic endocrine actions, these might hypothetically impact on adipose expansion or the vascular comorbidities of obesity. VASCULAR ENDOTHELIAL growth factor (VEGF) is a paracrine factor that stimulates local angiogenesis in response to hypoxia. Although classically regarded as an endothelial or vascular smooth muscle-derived hormone, a wide range of secretory tissues has been identified ( 1 ). Undoubtedly, the pathophysi Continue reading >>

Frontiers | Brown Adipose Tissue Activity As A Target For The Treatment Of Obesity/insulin Resistance | Physiology

Frontiers | Brown Adipose Tissue Activity As A Target For The Treatment Of Obesity/insulin Resistance | Physiology

Front. Physiol., 30 January 2015 | Brown adipose tissue activity as a target for the treatment of obesity/insulin resistance 1Laboratory of Metabolism, Department of Internal Medicine Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland 2Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland Presence of brown adipose tissue (BAT), characterized by the expression of the thermogenic uncoupling protein 1 (UCP1), has recently been described in adult humans. UCP1 is expressed in classical brown adipocytes, as well as in beige cells in white adipose tissue (WAT). The thermogenic activity of BAT is mainly controlled by the sympathetic nervous system. Endocrine factors, such as fibroblast growth factor 21 (FGF21) and bone morphogenic protein factor-9 (BMP-9), predominantly produced in the liver, were shown to lead to activation of BAT thermogenesis, as well as to browning of WAT. This was also observed in response to irisin, a hormone secreted by skeletal muscles. Different approaches were used to delineate the impact of UCP1 on insulin sensitivity. When studied under thermoneutral conditions, UCP1 knockout mice exhibited markedly increased metabolic efficiency due to impaired thermogenesis. The impact of UCP1 deletion on insulin sensitivity in these mice was not reported. Conversely, several studies in both rodents and humans have shown that BAT activation (by cold exposure, 3-agonist treatment, transplantation and others) improves glucose tolerance and insulin sensitivity. Interestingly, similar results were obtained by adipose tissue-specific overexpression of PR-domain-containing 16 (PRDM16) or BMP4 in mice. The mediators of such beneficial effects seem to include FGF21, interleukin-6, BMP8B and prostaglandin D2 synth Continue reading >>

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