Coordinated regulation of hormone-sensitive lipase and lipoprotein lipase in human adipose tissue in vivo: Implications for the control of fat storage and fat mobilization

Cortisol is known to increase whole body lipolysis, yet chronic hypercortisolemia results in increased fat mass. The main aim of the study was to explain these two apparently opposed observations by examining the acute effects of hypercortisolemia on lipolysis in subcutaneous adipose tissue and in the whole body. Six healthy subjects were studied on two occasions. On one occasion hydrocortisone sodium succinate was infused iv to induce hypercortisolemia (mean plasma cortisol concentrations, 1500 ± 100 vs. 335± 25 nmol/L; P < 0.001); on the other occasion (control study) no intervention was made. Lipolysis in the sc adipose tissue of the anterior abdominal wall was studied by measurement of arterio-venous differences, and lipolysis in the whole body was studied by constant infusion of[ 1,2,3-2H5]glycerol for measurement of the systemic glycerol appearance rate. Hypercortisolemia led to significantly increased arterialized plasma nonesterified fatty acid (NEFA; P < 0.01) and blood glycerol concentrations (P < 0.05), with an increase in systemic glycerol appearance (P < 0.05). However, in sc abdominal adipose tissue, hypercortisolemia decreased veno-arterialized differences for NEFA (P < 0.05) and reduced NEFA efflux (P < 0.05). This reduction was attributable to decreased intracellular lipolysis (P < 0.05), reflecting decreased hormone-sensitive lipase action in this adipose depot. Hypercortisolemia caused a reduction in arterialized plasma TAG concentrations (P < 0.05), but without a significant change in the local extraction of TAG (presumed to reflect the action of adipose tissue lipoprotein lipase). There was no significant difference in plasma insulin concentrations between the control and hypercortisolemia study. Site-specific regulation of the enzymes of intracellular lipolysis (hormone-sensitive lipase) and intravascular lipolysis (lipoprotein lipase) may explain the ability of acute cortisol treatment to increase systemic glycerol and NEFA appearance rates while chronically promoting net central fat deposition.

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Seasonal changes in hormone-sensitive and lipoprotein lipase mRNA concentrations in marmot white adipose tissue

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1992.262.2.r177 ◽

1992 ◽

Vol 262 (2) ◽

pp. R177-R181 ◽

Cited By ~ 9

Author(s):

B. E. Wilson ◽

S. Deeb ◽

G. L. Florant

Keyword(s):

Adipose Tissue ◽

Lipoprotein Lipase ◽

White Adipose Tissue ◽

Mass Gain ◽

The Body ◽

Hormone Sensitive Lipase ◽

Marmota Flaviventris ◽

Fasting Period ◽

Hormone Sensitive ◽

Clear Increase

White adipose tissue (WAT) and plasma samples were obtained from yellow-bellied marmots (Marmota flaviventris) throughout the year. Mean plasma triacylglycerol (TG), free fatty acids (FFAs), and glycerol were determined. There was a clear increase in FFAs and decrease in mean TG and glycerol during the hibernation period when animals were fasting, suggesting increased lipolysis. RNA was isolated from WAT biopsies at four times in the year: spring, summer, fall, and winter. There were significant changes in the relative levels of mRNA for lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) during the body mass cycle of the marmot. The relative levels of LPL mRNA are high during the mass gain phase of the year and that of HSL mRNA are high during the fasting period when endogenous lipid is utilized. These results suggest that the genes for LPL and HSL are regulated seasonally to control the adipose mass depot in marmots.

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Adipose Tissue Lipoprotein Lipase and Hormone-Sensitive Lipase

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/01.atv.17.10.2287 ◽

1997 ◽

Vol 17 (10) ◽

pp. 2287-2292 ◽

Cited By ~ 33

Author(s):

Signy Reynisdottir ◽

Bo Angelin ◽

Dominique Langin ◽

Hans Lithell ◽

Mats Eriksson ◽

...

Keyword(s):

Adipose Tissue ◽

Lipoprotein Lipase ◽

Hormone Sensitive Lipase ◽

Hormone Sensitive ◽

Adipose Tissue Lipoprotein Lipase

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Effects of DHEA on metabolic and endocrine functions of adipose tissue

Hormone Molecular Biology and Clinical Investigation ◽

10.1515/hmbci-2013-0009 ◽

2013 ◽

Vol 14 (2) ◽

Cited By ~ 5

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.

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Hormone-sensitive lipase – quantitation of enzyme and mRNA in small biopsies of human adipose tissue

Hamdan Medical Journal ◽

10.7707/hmj.v6i3.256 ◽

2013 ◽

Vol 6 (3) ◽

pp. 347

Author(s):

Najat Rashid ◽

Mansour AL-Zarouni

Keyword(s):

Adipose Tissue ◽

Human Adipose Tissue ◽

Hormone Sensitive Lipase ◽

Hormone Sensitive

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

Molecular and Cellular Biology ◽

10.1128/mcb.00244-16 ◽

2016 ◽

Vol 36 (14) ◽

pp. 1961-1976 ◽

Cited By ~ 91

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.

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