Of mice and women: the β3-adrenergic receptor leptin and obesity

1996 ◽  
Vol 74 (5) ◽  
pp. 615-622 ◽  
Author(s):  
Nicole Bégin-Heick
Keyword(s):  
Adipose Tissue ◽  
G Proteins ◽  
Adrenergic Receptor ◽  
Metabolic Response ◽  
Human Adipose Tissue ◽  
Hormone Sensitive Lipase ◽  
Camp Production ◽  
Ob Gene ◽  
Hormone Sensitive

The metabolic response of adipose tissue to stimuli leading to lipid mobilization is important in determining the direction of metabolism and the degree to which adipose tissue can store lipids and release fatty acids in times of need. The lipolytic machinery is controlled by the activity of hormone-sensitive lipase, which in turn is controlled by the cellular levels of cAMP. The production of cAMP is abnormal in the adipose tissue of some animal models of obesity. In the ob/ob mouse, the defective cAMP production has been associated with deficient levels of some of the isoforms of the guanine nucleotide transducing G-proteins and also with the low expression and functionality of the β3-adrenergic receptor (β3-AR). The recent discovery of the ob gene product leptin calls into question the role of the ob gene in the regulation of the cAMP cascade in adipose tissue. The importance of the β3-AR and leptin in regulating human adipose tissue metabolism remains to be clarified.Key words: ob gene, lipolysis, adenylyl cyclase, G-proteins, obesity, adipose tissue, beta-adrenergic receptor.

Effects of DHEA on metabolic and endocrine functions of adipose tissue

2013 ◽  
Vol 14 (2) ◽  
Author(s):  
Joanna Karbowska ◽  
Zdzislaw Kochan
Keyword(s):  
Adipose Tissue ◽  
Human Adipose Tissue ◽  
Hormone Sensitive Lipase ◽  
Peroxisome Proliferator ◽  
Tissue Mass ◽  
Triacylglycerol Hydrolysis ◽  
Proliferation And Differentiation ◽  
Hormone Sensitive ◽  
Hormone Biosynthesis ◽  
Peroxisome Proliferator Activated Receptors

AbstractDehydroepiandrosterone (DHEA) and its sulfate ester, DHEAS, are the major circulating adrenal steroids and serve as substrates for sex hormone biosynthesis. DHEA is effectively taken up by adipose tissue, where the concentrations of free DHEA are four to ten times higher than those found in the circulation. DHEA reduces adipose tissue mass and inhibits the proliferation and differentiation of adipocytes; it may also protect against obesity by lowering the activity of stearoyl-CoA desaturase 1 in fat cells. Recent studies demonstrate that DHEA stimulates triacylglycerol hydrolysis in adipose tissue by increasing the expression and activity of adipose triglyceride lipase and hormone-sensitive lipase, the key enzymes of lipolysis. DHEA has been shown to modulate insulin signaling pathways, enhance glucose uptake in adipocytes, and increase insulin sensitivity in patients with DHEA deficiency or abnormal glucose tolerance. Additionally, by suppressing the activity of 11β-hydroxysteroid dehydrogenase 1 in adipocytes, DHEA may promote intra-adipose inactivation of cortisol to cortisone. Several studies have demonstrated that DHEA may also regulate the expression and secretion of adipokines such as leptin, adiponectin, and resistin. The effects of DHEA on adipokine expression in adipose tissue are depot-specific, with visceral fat being the most responsive. The mechanisms underlying DHEA actions in adipose tissue are still unclear; however, they involve nuclear receptors such as androgen receptor and peroxisome proliferator-activated receptors γ and α. Because clinical trials investigating the effects of DHEA failed to yield consistent results, further studies are needed to clarify the role of DHEA in the regulation of human adipose tissue physiology.

scholarly journals AMPK Phosphorylates Desnutrin/ATGL and Hormone-Sensitive Lipase To Regulate Lipolysis and Fatty Acid Oxidation within Adipose Tissue

2016 ◽  
Vol 36 (14) ◽  
pp. 1961-1976 ◽  
Author(s):  
Sun-Joong Kim ◽  
Tianyi Tang ◽  
Marcia Abbott ◽  
Jose A. Viscarra ◽  
Yuhui Wang ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Protein Kinase ◽  
Hydrolase Activity ◽  
Hormone Sensitive Lipase ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Hormone Sensitive

The role of AMP-activated protein kinase (AMPK) in promoting fatty acid (FA) oxidation in various tissues, such as liver and muscle, has been well understood. However, the role of AMPK in lipolysis and FA metabolism in adipose tissue has been controversial. To investigate the role of AMPK in the regulation of adipose lipolysisin vivo, we generated mice with adipose-tissue-specific knockout of both the α1 and α2 catalytic subunits of AMPK (AMPK-ASKO mice) by using aP2-Cre and adiponectin-Cre. Both models of AMPK-ASKO ablation show no changes in desnutrin/ATGL levels but have defective phosphorylation of desnutrin/ATGL at S406 to decrease its triacylglycerol (TAG) hydrolase activity, lowering basal lipolysis in adipose tissue. These mice also show defective phosphorylation of hormone-sensitive lipase (HSL) at S565, with higher phosphorylation at protein kinase A sites S563 and S660, increasing its hydrolase activity and isoproterenol-stimulated lipolysis. With higher overall adipose lipolysis, both models of AMPK-ASKO mice are lean, having smaller adipocytes with lower TAG and higher intracellular free-FA levels. Moreover, FAs from higher lipolysis activate peroxisome proliferator-activated receptor delta to induce FA oxidative genes and increase FA oxidation and energy expenditure. Overall, for the first time, we providein vivoevidence of the role of AMPK in the phosphorylation and regulation of desnutrin/ATGL and HSL and thus adipose lipolysis.

The atrial natriuretic peptide- and catecholamine-induced lipolysis and expression of related genes in adipose tissue in hypothyroid and hyperthyroid patients

2007 ◽  
Vol 293 (1) ◽  
pp. E246-E251 ◽  
Author(s):  
J. Polak ◽  
C. Moro ◽  
E. Klimcakova ◽  
M. Kovacikova ◽  
M. Bajzova ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Atrial Natriuretic Peptide ◽  
Thyroid Hormones ◽  
Natriuretic Peptide ◽  
Hormone Sensitive Lipase ◽  
Hormone Sensitive ◽  
Hyperthyroid Patients ◽  
Atrial Natriuretic

Thyroid dysfunction is associated with several abnormalities in intermediary metabolism, including impairment of lipolytic response to catecholamines in subcutaneous abdominal adipose tissue (SCAAT). Atrial natriuretic peptide (ANP) is a powerful lipolytic peptide; however, the role of ANP-mediated lipolysis in thyroid disease has not been elucidated. The aim of this study was to investigate the role of thyroid hormones in the regulation of ANP-induced lipolysis as well as in the gene expression of hormone-sensitive lipase, phosphodiesterase 3B (PDE3B), uncoupling protein-2 (UCP2), natriuretic peptide receptor type A, and β2-adrenergic receptor in SCAAT of hyperthyroid and hypothyroid patients. Gene expression in SCAAT was studied in 13 hypothyroid and 11 hyperthyroid age-matched women before and 2–4 mo after the normalization of their thyroid status. A microdialysis study was performed on a subset of nine hyperthyroid and 10 hypothyroid subjects. ANP- and isoprenaline-induced lipolyses were higher in hyperthyroid subjects, with no differences between the groups following treatment. Hormone-sensitive lipase gene expression was higher in hyperthyroid compared with hypothyroid subjects before treatment, whereas no difference was observed following treatment. No differences in gene expression of other genes were observed between the two groups. Following treatment, the gene expression of UCP2 decreased in hyperthyroid, whereas the expression of PDE3B decreased in hypothyroid subjects. We conclude that thyroid hormones regulate ANP- and isoprenaline-mediated lipolysis in human SCAAT in vivo. Increased lipolytic subcutaneous adipose tissue response in hyperthyroid patients may involve postreceptor signaling mechanisms.

scholarly journals Acetylation of Cavin-1 Promotes Lipolysis in White Adipose Tissue

2017 ◽  
Vol 37 (16) ◽  
Author(s):  
Shui-Rong Zhou ◽  
Liang Guo ◽  
Xu Wang ◽  
Yang Liu ◽  
Wan-Qiu Peng ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Molecular Mechanisms ◽  
Hormone Sensitive Lipase ◽  
Dependent Manner ◽  
Nutritional Regulation ◽  
Fat Mobilization ◽  
Hormone Sensitive ◽  
Shed Light

ABSTRACT White adipose tissue (WAT) serves as a reversible energy storage depot in the form of lipids in response to nutritional status. Cavin-1, an essential component in the biogenesis of caveolae, is a positive regulator of lipolysis in adipocytes. However, molecular mechanisms of cavin-1 in the modulation of lipolysis remain poorly understood. Here, we showed that cavin-1 was acetylated at lysines 291, 293, and 298 (3K), which were under nutritional regulation in WAT. We further identified GCN5 as the acetyltransferase and Sirt1 as the deacetylase of cavin-1. Acetylation-mimetic 3Q mutants of cavin-1 augmented fat mobilization in 3T3-L1 adipocytes and zebrafish. Mechanistically, acetylated cavin-1 preferentially interacted with hormone-sensitive lipase and recruited it to the caveolae, thereby promoting lipolysis. Our findings shed light on the essential role of cavin-1 in regulating lipolysis in an acetylation-dependent manner in WAT.

Activation of nucleotide oligomerization domain containing protein 1 induces lipolysis through NF-κB and the lipolytic PKA activation in 3T3-L1 adipocytes

2013 ◽  
Vol 91 (6) ◽  
pp. 428-434 ◽  
Author(s):  
Jaanki S. Purohit ◽  
Pan Hu ◽  
Guoxun Chen ◽  
Jay Whelan ◽  
Naima Moustaid-Moussa ◽  
...  
Keyword(s):  
Hormone Sensitive Lipase ◽  
Dependent Manner ◽  
Camp Production ◽  
Nucleotide Oligomerization ◽  
Hormone Sensitive ◽  
Sirna Knockdown ◽  
Dose Dependent ◽  
Nucleotide Oligomerization Domain ◽  
Oligomerization Domain

Obesity is associated with chronic inflammation. Toll-like receptors (TLR) and NOD-like receptors (NLR) are two families of pattern recognition receptors that play important roles in the immune response and inflammation in adipocytes. Activation of TLR4 has been shown to stimulate lipolysis from adipose tissue or adipocytes. However, effects of activation of nucleotide-oligomerization domain containing protein 1 (NOD1), one of the prominent members of NLRs, on adipocyte lipolysis have not been studied. Here we report that NOD1 activation by the synthetic ligands (Tri-DAP and C12-iEDAP) stimulated lipolysis in 3T3-L1 adipocytes in a time- and dose-dependent manner. C12-iEDAP-induced lipolysis was attenuated with NOD1 siRNA knockdown, demonstrating the specificity of the effects. Moreover, inhibition of the protein kinase A (PKA)/hormone sensitive lipase (HSL) and NF-κB pathways by the pharmacological inhibitors attenuated the lipolytic effects of C12-iEDAP. Furthermore, we show NOD1 activation induced PKA activation independent of cAMP production and inhibition of NF-κB pathways attenuated phosphorylation of selected PKA lipolytic targets (phosphorylation of Perilipin Ser 517 and HSL Ser 563). Taken together, our results demonstrate a novel role of NOD1 activation, via NF-κB/PKA lipolytic activation, in inducing lipolysis in adipocytes and suggest that NOD1 activation may contribute to dyslipidemia in obesity.

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