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What Does Insulin Do In Lipolysis?

Brain Insulin Controls Adipose Tissue Lipolysis And Lipogenesis - Sciencedirect

Brain Insulin Controls Adipose Tissue Lipolysis And Lipogenesis - Sciencedirect

Volume 13, Issue 2 , 2 February 2011, Pages 183-194 Brain Insulin Controls Adipose Tissue Lipolysis and Lipogenesis White adipose tissue (WAT) dysfunction plays a key role in the pathogenesis of type 2 diabetes (DM2). Unrestrained WAT lipolysis results in increased fatty acid release, leading to insulin resistance and lipotoxicity, while impaired de novo lipogenesis in WAT decreases the synthesis of insulin-sensitizing fatty acid species like palmitoleate. Here, we show that insulin infused into the mediobasal hypothalamus (MBH) of Sprague-Dawley rats increases WAT lipogenic protein expression, inactivates hormone-sensitive lipase (Hsl), and suppresses lipolysis. Conversely, mice that lack the neuronal insulin receptor exhibit unrestrained lipolysis and decreased de novo lipogenesis in WAT. Thus, brain and, in particular, hypothalamic insulin action play a pivotal role in WAT functionality. Insulin signaling suppresses lipolysis by reducing sympathetic output to fat tissue Neuronal insulin signaling induces de novo lipogenesis in adipose tissue Impairment of hypothalamic insulin signaling unrestrains adipose tissue lipolysis Continue reading >>

Abdominal Subcutaneous And Visceral Adipocyte Size, Lipolysis And Inflammation Relate To Insulin Resistance In Male Obese Humans

Abdominal Subcutaneous And Visceral Adipocyte Size, Lipolysis And Inflammation Relate To Insulin Resistance In Male Obese Humans

Abdominal subcutaneous and visceral adipocyte size, lipolysis and inflammation relate to insulin resistance in male obese humans Scientific Reportsvolume8, Articlenumber:4677 (2018) | Download Citation Obesity is associated with a disturbed adipose tissue (AT) function characterized by adipocyte hypertrophy, an impaired lipolysis and pro-inflammatory phenotype, which contributes to insulin resistance (IR). We investigated whether AT phenotype in different AT depots of obese individuals with and without type 2 diabetes mellitus (T2DM) is associated with whole-body IR. Subcutaneous (SC) and visceral (V) AT biopsies from 18 lean, 17 obese and 8 obese T2DM men were collected. AT phenotype was characterized by ex vivo measurement of basal and stimulated lipolysis (mature adipocytes), adipocyte size distribution (AT tissue sections) and AT immune cells (flow cytometry). In VAT, mean adipocyte size, CD45+ leukocytes and M1 macrophages were significantly increased in both obese groups compared to lean individuals. In SCAT, despite adipocyte hypertrophy, no significant differences in immune cell populations between groups were found. In SCAT, multiple linear regression analysis showed that none of the AT phenotype markers independently contributed to HOMA-IR while in VAT, mean adipocyte sizewas significantly related to HOMA-IR. In conclusion, beside adipocyte hypertrophy in VAT, M1 macrophage- or B-cell-mediated inflammation, may contribute to IR, while inflammation in hypertrophic SCAT does not seem to play a major role in IR. During the development of obesity, adipose tissue (AT) expansion frequently results in adipocyte hypertrophy (i.e. enlargement of the adipocyte), which is a known stressor for adipocytes 1 . Increases in AT mass and adipocyte volume result in a broad ran Continue reading >>

Fasting And Lipolysis – Part 4

Fasting And Lipolysis – Part 4

Insulin is the main driver of both obesity and type 2 diabetes. The key to reversing both conditions is therefore not “How do we reduce calories?”, but instead “How do we reduce Insulin?” There are almost no drugs that will do this. There is actually two classes of medications that consistently reduces insulin – one by a lot, one by a little. Not by co-incidence, they are the only drugs that consistently reduces weight. But the problem is that they are both expensive and have side effects. Short of drugs, we need an efficient, effective way to lower insulin if we are to be successful in losing weight. A diet low in refined carbs and sugar will certainly do the trick for some, but for others it is not enough. The answer, if you haven’t guessed yet, is fasting. The classic descriptions of fasting physiology were written by Dr. George Cahill. We reviewed this in a previous post, but here’s a pictorial version. Essentially, fasting is the gradual shift of burning glucose to burning fat. In stage 1, most of the body is using exogenous glucose. By stage 2 and 3, glycogen (stored sugar) provides much of the glucose needed. Most tissues are still using sugar, but the liver, muscle and fat cells have started to burn fat. By stage 4 and 5, glycogen stores have run out. Hepatic and renal (liver and kidney) gluconeogenesis is now providing all the glucose, but only the brain, red blood cells and the renal medulla (the inner part of the kidney) uses glucose. Everything else has shifted over to burning fat. By stage 5, the brain has mostly shifted to burning fat in the form of ketone bodies. Only a small amount of glucose is needed for red blood cells. You can see that the origin of the blood glucose gradually switches from exogenous (dietary) to gluconeogenesis made fr Continue reading >>

Insulin And Glucagon

Insulin And Glucagon

Acrobat PDF file can be downloaded here. The islets of Langerhans The pancreatic Islets of Langerhans are the sites of production of insulin, glucagon and somatostatin. The figure below shows an immunofluorescence image in which antibodies specific for these hormones have been coupled to differing fluorescence markers. We can therefore identify those cells that produce each of these three peptide hormones. You can see that most of the tissue, around 80 %, is comprised of the insulin-secreting red-colored beta cells (ß-cells). The green cells are the α-cells (alpha cells) which produce glucagon. We see also some blue cells; these are the somatostatin secreting γ-cells (gamma cells). Note that all of these differing cells are in close proximity with one another. While they primarily produce hormones to be circulated in blood (endocrine effects), they also have marked paracrine effects. That is, the secretion products of each cell type exert actions on adjacent cells within the Islet. An Introduction to secretion of insulin and glucagon The nutrient-regulated control of the release of these hormones manages tissue metabolism and the blood levels of glucose, fatty acids, triglycerides and amino acids. They are responsible for homeostasis; the minute-to-minute regulation of the body's integrated metabolism and, thereby, stabilize our inner milieu. The mechanisms involved are extremely complex. Modern medical treatment of diabetes (rapidly becoming "public enemy number one") is based on insight into these mechanisms, some of which are not completely understood. I will attempt to give an introduction to this complicated biological picture in the following section. Somewhat deeper insight will come later. The Basics: secretion Let us begin with two extremely simplified figur Continue reading >>

Lipolysis

Lipolysis

Lipolysis /lɪˈpɒlɪsɪs/ is the breakdown of lipids and involves hydrolysis of triglycerides into glycerol and free fatty acids. Predominantly occurring in adipose tissue, lipolysis is used to mobilize stored energy during fasting or exercise. Lipolysis is directly induced in adipocytes by glucagon,[1] epinephrine, norepinephrine, growth hormone, atrial natriuretic peptide, brain natriuretic peptide, and cortisol.[2] Mechanisms[edit] This image illustrates the three separate steps of hydrolysis involved in lipolysis. In the first step, triacylglycerol is hydrolyzed to make diacylglycerol and this is catalyzed by adipose triglyceride lipase (ATGL). In the second step, diacylglycerol is hydrolyzed to make monoacylglycerol and this is catalyzed by hormone-sensitive lipase (HSL). In the last step, monoacylglycerol is hydrolyzed to make glycerol and this is catalyzed by monoacylglycerol lipase (MGL). In adipose tissue, intracellular triglycerides are stored in cytoplasmic lipid droplets. When lipases are phosphorylated, they access lipid droplets and through multiple steps of hydrolysis, breakdown triglycerides into fatty acids and glycerol. Each step of hydrolysis leads to the removal of one fatty acid. The first step and the rate-limiting step of lipolysis is carried out by adipose triglyceride lipase (ATGL). This enzyme catalyzes the hydrolysis of triacylglycerol to diacylglycerol. Subsequently, hormone-sensitive lipase (HSL) catalyzes the hydrolysis of diacylglycerol to monoacylglycerol and monoacylglycerol lipase (MGL) catalyzes the hydrolysis of monoacylglycerol to glycerol.[3] Perilipin 1A is a key protein regulator of lipolysis in adipose tissue. This lipid droplet-associated protein, when deactivated, will prevent the interaction of lipases with triglycerides in Continue reading >>

Insulin And Lipolysis

Insulin And Lipolysis

The fat stores in your body are metabolically active and dynamic tissues. Two opposing forces determine the amount of fat you carry around from day to day. Lipogenesis is the process that converts sugars to fats, which are subsequently deposited and stored in fat tissue. Lipolysis is the process of fat breakdown, typically to generate energy. These two metabolic activities are controlled by hormones secreted by your pancreas, pituitary and adrenal glands, and ovaries or testes. The pancreatic hormone insulin is particularly important in fat metabolism and lipolysis. Video of the Day Insulin is secreted from pancreatic cells in response to rising levels of glucose in your bloodstream. The consumption of food -- particularly proteins and carbohydrates -- prompts the release of insulin from your pancreas. In contrast, fasting and a falling blood sugar reduce insulin production and release. Insulin triggers the absorption of glucose by muscle, liver and fat cells, thereby lowering the blood sugar level. In addition, insulin stimulates the uptake of fatty acids by fat cells, which convert these molecules into triglycerides -- the primary storage form of fat in your body. Thus, insulin promotes lipogenesis. When your energy needs increase or your blood glucose level falls, the production of hormones that mobilize your energy stores begins to rise. These hormones -- such as glucagon and adrenalin -- stimulate lipolysis, which involves the breakdown of triglycerides stored in your fat tissue. The fatty acids and glycerol molecules liberated by lipolysis are then metabolized to generate energy to meet your needs. The hormones that oppose insulin and stimulate lipolysis are called glucose counter-regulatory hormones. The hormones that control lipolysis and lipogenesis do more tha Continue reading >>

Insulin Inhibits Lipolysis In Adipocytes Via The Evolutionarily Conserved Mtorc1-egr1-atgl-mediated Pathway

Insulin Inhibits Lipolysis In Adipocytes Via The Evolutionarily Conserved Mtorc1-egr1-atgl-mediated Pathway

Insulin Inhibits Lipolysis in Adipocytes via the Evolutionarily Conserved mTORC1-Egr1-ATGL-Mediated Pathway Boston University School of Medicine, Boston, Massachusetts, USA One of the basic functions of insulin in the body is to inhibit lipolysis in adipocytes. Recently, we have found that insulin inhibits lipolysis and promotes triglyceride storage by decreasing transcription of adipose triglyceride lipase via the mTORC1-mediated pathway (P. Chakrabarti et al., Diabetes 59:775781, 2010), although the mechanism of this effect remained unknown. Here, we used a genetic screen in Saccharomyces cerevisiae in order to identify a transcription factor that mediates the effect of Tor1 on the expression of the ATGL ortholog in yeast. This factor, Msn4p, has homologues in mammalian cells that form a family of early growth response transcription factors. One member of the family, Egr1, is induced by insulin and nutrients and directly inhibits activity of the ATGL promoter in vitro and expression of ATGL in cultured adipocytes. Feeding animals a high-fat diet increases the activity of mTORC1 and the expression of Egr1 while decreasing ATGL levels in epididymal fat. We suggest that the evolutionarily conserved mTORC1-Egr1-ATGL regulatory pathway represents an important component of the antilipolytic effect of insulin in the mammalian organism. Current epidemics of metabolic diseases, such as type 2 diabetes, cardiac dysfunction, hypertension, hepatic steatosis, etc., are largely caused by widespread obesity. Although obesity can affect human health via several different mechanisms, the best-established connection between obesity and metabolic disease is elevated and/or dysregulated levels of circulating free fatty acids (FFA). In addition to their direct pathological effects, super Continue reading >>

Fatty Acids, Obesity, And Insulin Resistance: Time For A Reevaluation

Fatty Acids, Obesity, And Insulin Resistance: Time For A Reevaluation

There is a widespread acceptance in the literature that plasma nonesterified fatty acids (NEFA), also called free fatty acids (FFA), can mediate many adverse metabolic effects, most notably insulin resistance. Elevated NEFA concentrations in obesity are thought to arise from an increased adipose tissue mass. It is also argued that the process of fatty acid mobilization from adipose tissue, normally suppressed by insulin, itself becomes insulin resistant—thus, lipolysis is further increased, potentially leading to a vicious cycle. Although we have also accepted this model for many years (1,2), recently there has been a steady accumulation of data, both in the literature and from our own research, that has forced us to realize that this simple story is not always true. Here we review the background to the idea of “fatty acids as metabolic villains,” together with data from the literature and from our own studies, which tend to show another side to the fatty acids/insulin resistance story. We will first examine the relationship between systemic concentrations of NEFA and obesity/insulin resistance and then study adipose tissue in the obese state with regard to its adaptation for NEFA release. FATTY ACIDS AND METABOLIC PHYSIOLOGY NEFA circulate in the plasma bound to plasma albumin. Their function was largely elucidated in the 1950s through the work of Vincent Dole (3) at the Rockefeller Institute in New York and Robert Gordon (4,5) at the National Institutes of Health. Gordon demonstrated the origin of plasma NEFA from adipose tissue and their use by tissues such as the liver and myocardium, but not the brain. We now recognize that NEFA are the vehicle by which triacylglycerol (TG) stored in adipose tissue is transported to its sites of utilization. NEFA turnover is Continue reading >>

Physiological Levels Of Glucagon Do Not Influence Lipolysis In Abdominal Adipose Tissue As Assessed By Microdialysis

Physiological Levels Of Glucagon Do Not Influence Lipolysis In Abdominal Adipose Tissue As Assessed By Microdialysis

To determine whether glucagon stimulates lipolysis in adipose tissue, seven healthy young male volunteers were studied, with indwelling microdialysis catheters placed sc in abdominal adipose tissue. Subjects were studied three times: 1) during euglucagonemia (EG; glucagon infusion rate, 0.5 ng/kgmin); 2) during hyperglucagonemia (HG; (glucagon infusion rate, 1.5 ng/kgmin); and 3) during EG and a concomitant glucose infusion mimicking the glucose profile from the day of HG (EG+G). Somatostatin (450 g/h) was infused to suppress hormonal secretion, and replacement doses of insulin and GH were administered. Sampling was done every 30 min for 420 min. Baseline circulating values of insulin, C-peptide, glucagon, GH, glycerol, and free fatty acids were comparable in all three conditions. During EG and EG+G, plasma glucagon was maintained at fasting level (2040 ng/L); whereas, during HG, it increased (110130 ng/L). Interstitial concentrations of glycerol were similar in the three conditions[ 30,870 5,946 (EG) vs. 31,074 7,092 (HG) vs. 29,451 6,217 (EG+G) mol/L120 min, P = 0.98]. Plasma glycerol (ANOVA, P = 0.5) and free fatty acids (ANOVA, P = 0.3) were comparable during the different glucagon challenges. We conclude that HG per se does not increase interstitial glycerol (and thus lipolysis) in abdominal sc adipose tissue; nor does modest hyperglycemia, during basal insulinemia and glucagonemia, influence indices of abdominal sc lipolysis. A DISTURBED PANCREATIC islet function is the main pathophysiological feature of type I diabetes mellitus. In addition to insulin deficiency (absolute or relative), hypersecretion of glucagon is present. The glucagon excess is most pronounced in poorly controlled diabetes mellitus, but circulating levels are raised, even in well-controlled di Continue reading >>

Obesity And Insulin Resistance: The Lipolysis Route

Obesity And Insulin Resistance: The Lipolysis Route

> Obesity and insulin resistance: the lipolysis route Obesity and insulin resistance: the lipolysis route Press release | 20 Feb 2013 - 10h15 | By INSERM PRESS OFFICE Liver and skeletal muscle resistance to the action of insulin is an early sign of the development of Type 2 Diabetes. The INSERM team at the Obesity Research Laboratory in the Institut des Maladies Mtaboliques and Cardiovasculaires (INSERM / Universit Toulouse III Paul Sabatier), headed by Dominique Langin, has shown through results published this week, that there is an association between lipolysis (mobilisation of fat in response to the bodys need for energy) and insulin sensitivity in humans. Researchers also showed that a reduction in lipolysis in mice, through genetic modification or pharmacological treatment, improved the action of insulin on glucose metabolism in the liver and the muscles. Lipolysis inhibition could be used in treating insulin resistance in the obese. The results are accessible on the website of the Plos Biology journal for 19 February 2013. Insulin is the hormone that controls the blood glucose level, inhibiting its production by the liver and stimulating its use in the muscles. When the body needs energy, during fasting or due to physical exercise, the triglycerides stored in the adipose tissue are released in the form of fatty acids through the action of adipocyte lipolysis. When this happens, the fatty acids have a favourable action because they are supplying energy. These fatty acids may also have a deleterious action, however. When they are present in excessive quantities, as in the case of obesity, they are deposited in the peripheral organs and interfere with the action of insulin. Other lipids and proteins produced by an excess of adipose tissue are also involved in the de Continue reading >>

Lipolysis And Lipogenesis

Lipolysis And Lipogenesis

Triglyceride, a fatty acyl ester derivative of glycerol, is the major energy depot of all eukaryotic cells. Lipolysis is the enzymic process by which triacylglycerol, stored in cellular lipid droplets, is hydrolytically cleaved to generate glycerol and free fatty acids. The free fatty acids can be subsequently used as energy substrates, essential precursors for lipid and membrane synthesis, or mediators in cell signaling processes. The complete oxidation of free fatty acids to generate ATP occurs in the mitochondria by the processes of β-oxidation which is described in the related article Fatty acid oxidation and synthesis. It involves the sequential degradation of fatty acids to multiple units of acetyl-CoA which can then be completely oxidized via the tricarboxylic acid cycle (Krebs Cycle) and electron transport chain. Lipogenesis is the process by which glycerol is esterified with free fatty acids to form triglyceride. Dietary fat (triglycerides), when ingested with food, is absorbed by the gut. Being apolar (poorly water-soluble), triglycerides are transported in the form of plasma-lipoproteins called chylomicrons. Lipids are released from their carrier lipoproteins through the local activity of lipoprotein lipase (LPL) and subsequently split into their constituent fatty acids and glycerol. These are taken up by adipose tissue where the triglycerides are resynthesized and stored in cytoplasmic lipid droplets. Lipogenesis also includes the anabolic process by which triglycerides are formed in the liver from excess glucose. Here fatty acids of varying length are synthesised by the sequential addition of two-carbon units derived from acetyl CoA as discussed in the related article Fatty acid oxidation and synthesis. Fatty acids generated by lipogenesis in the liver, ar Continue reading >>

Jci -causal Linkage Between Insulin Suppression Of Lipolysis And Suppression Of Liver Glucose Output In Dogs.

Jci -causal Linkage Between Insulin Suppression Of Lipolysis And Suppression Of Liver Glucose Output In Dogs.

Causal linkage between insulin suppression of lipolysis and suppression of liver glucose output in dogs. J Clin Invest. 1996; 98(3) :741-749. . Suppression of hepatic glucose output (HGO) has been shown to be primarily mediated by peripheral rather than portal insulin concentrations; however, the mechanism by which peripheral insulin suppresses HGO has not yet been determined. Previous findings by our group indicated a strong correlation between free fatty acids (FFA) and HGO, suggesting that insulin suppression of HGO is mediated via suppression of lipolysis. To directly test the hypothesis that insulin suppression of HGO is causally linked to the suppression of adipose tissue lipolysis, we performed euglycemic-hyperinsulinemic glucose clamps in conscious dogs (n = 8) in which FFA were either allowed to fall or were prevented from falling with Liposyn plus heparin infusion (LI; 0.5 ml/min 20% Liposyn plus 25 U/min heparin with a 250 U prime). Endogenous insulin and glucagon were suppressed with somatostatin (1 microgram/min/kg), and insulin was infused at a rate of either 0.125 or 0.5 mU/min/kg. Two additional experiments were performed at the 0.5 mU/min/kg insulin dose: a double Liposyn infusion (2 x LI; 1.0 ml/min 20% Liposyn, heparin as above), and a glycerol infusion (19 mg/min). With the 0.125 mU/min/kg insulin infusion, FFA fell 40% and HGO fell 33%; preventing the fall in FFA with LI entirely prevented this decline in HGO. With 0.5 mU/min/kg insulin infusion, FFA levels fell 64% while HGO declined 62%. Preventing the [] Continue reading >>

Lipolysis - An Overview | Sciencedirect Topics

Lipolysis - An Overview | Sciencedirect Topics

Larry R. Engelking, in Textbook of Veterinary Physiological Chemistry (Third Edition) , 2015 Epinephrine, thyroxine, and cortisol are potent lipolytic hormones in most domestic animals. Interleukin-6 may be an important lipolytic agent released from exercising muscle tissue. Insulin and insulin-like growth factor-1 possess antilipolytic activity. Adipocytes contain several gluconeogenic enzymes. Glyceroneogenesis modulates FFA release from adipocytes during starvation. Adipocyte lipolysis and glyceroneogenesis are largely cAMP-dependent processes. Glucocorticoids promote lipolysis through a cAMP-independent pathway. Leptin is a protein hormone produced by adipocytes that promotes satiety. Brown adipose tissue oxidizes FFAs, and is specialized for heat production. Rianne van der Spek*, ... Andries Kalsbeek, in Progress in Brain Research , 2012 Lipolysis is the catabolic process leading to the breakdown of triacylglycerols (TAGs) into FFAs and glycerol. After release into the blood, FFAs are transported and taken up by other tissues to be utilized for -oxidation and subsequent ATP generation. Some FFAs do not leave the fat cell and are reesterified into intracellular TAG. During lipolysis, intracellular TAG undergoes hydrolysis through the action of three major lipases: adipose triglyceride lipase (ATGL/desnutrin/phospholipase A2), HSL, and monoacylglycerol (MGL) lipase. ATGL hydrolyses TAGs into diacylglycerol (DAG) and one FA, followed by HSL converting DAG into monoacylglycerol (MAG) plus one FA, MGL then hydrolyses MAG to produce glycerol and a third FA (Ahmadian et al., 2010; Lafontan and Langin, 2009). Lipolysis is regulated by the ANS (Bartness et al., 2010a) and by several humoral factors, such as catecholamines (phosphorylation of HSL), glucocorticoids (upregula Continue reading >>

Metabolic Coupling In Pancreatic Beta Cells: Lipolysis Revisited

Metabolic Coupling In Pancreatic Beta Cells: Lipolysis Revisited

, Volume 59, Issue12 , pp 25102513 | Cite as Metabolic coupling in pancreatic beta cells: lipolysis revisited Adipose triglyceride lipaseBeta cellsHormone-sensitive lipaseLipolysisMetabolic coupling In this issue of Diabetologia, Marc Prentki and his group [ 1 ] add another piece to the puzzle of how lipids are involved in the metabolic control of insulin secretion. While it is generally accepted that increases in blood glucose are transmitted into metabolic changes inside the beta cell, triggering secretion of insulin, the way in which insulin secretion is amplified and sustained is less clear but likely as important,. The work by Attan and colleagues [ 1 ] enhances our understanding of the role of lipid metabolism in this context and may shed further light on why insulin secretion fails in type 2 diabetes. In the article, the authors inactivated adipose triglyceride lipase (ATGL) in pancreatic beta cells [ 1 ]. This enzyme is a catalyst for the first committed step in the breakdown of triacylglycerols (Fig. 1 ) [ 2 ]; it hydrolyses triacylglycerols to diacylglycerols. These are then hydrolysed by the hormone-sensitive lipase (HSL) into monoacylglycerols, which are finally degraded to fatty acids and glycerol [ 1 ]. Needless to say, this is a crucial series of metabolic reactions in adipose tissue, allowing our body to access energy in fasting states and during starvation. However, it is generally less appreciated that cells, other than fat cells, may utilise the same reactions, albeit for different purposes. Lipid signaling in the pancreatic beta cell. Cellular stores of triacylglycerol are hydrolysed by ATGL and HSL to diacylglycerol. In the next rate-limiting step of lipolysis, HSL hydrolyses diacylglycerol to monoacylglycerol. Monoacylglycerol has been proposed to Continue reading >>

Adipose Tissue Lipolysis And Insulin Sensitivity

Adipose Tissue Lipolysis And Insulin Sensitivity

Endocrine Abstracts (2013) 32 S32.3 | DOI: 10.1530/endoabs.32.S32.3 Adipose tissue lipolysis and insulin sensitivity Institute of Metabolic and Cardiovascular Disease, Toulouse, France. When energy is needed, white adipose tissue (WAT) provides fatty acids (FA) for use in peripheral tissues via stimulation of fat cell lipolysis. FA have been postulated to play a critical role in the development of obesity-induced insulin resistance, a major risk factor for diabetes and cardiovascular disease. However, whether and how chronic inhibition of fat mobilization from WAT modulates insulin sensitivity remains elusive. Hormone-sensitive lipase (HSL) participates in the breakdown of WAT triacylglycerol into FA. HSL haploinsufficiency and treatment with a HSL inhibitor resulted in improvement of insulin tolerance without impact on body weight and fat mass in high fat diet-fed mice. Notably, WAT inflammation was not modified. In vivo palmitate turnover analysis revealed that blunted lipolytic capacity is associated with diminution in FA uptake and storage in peripheral tissues of obese HSL haploinsufficient mice. The reduction in FA turnover was accompanied by an improvement of glucose metabolism with a shift in respiratory quotient, increase of glucose uptake in WAT and skeletal muscle and, enhancement of de novo lipogenesis and insulin signalling in liver. In human adipocytes, HSL gene silencing led to improved insulin-stimulated glucose uptake resulting in increased de novo lipogenesis and activation of cognate gene expression. In clinical studies, WAT lipolytic rate was positively and negatively correlated with indexes of insulin resistance and WAT de novo lipogenesis gene expression, respectively. In obese individuals, chronic inhibition of lipolysis resulted in induction of Continue reading >>

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