scholarly journals An Epistatic Interaction between Pnpla2 and Lipe Reveals New Pathways of Adipose Tissue Lipolysis

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 395 ◽  
Author(s):  
Xiao Zhang ◽  
Cong Cong Zhang ◽  
Hao Yang ◽  
Krishnakant G. Soni ◽  
Shu Pei Wang ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Epistatic Interaction ◽  
Hydrolase Activity ◽  
Hormone Sensitive Lipase ◽  
Adipose Triglyceride Lipase ◽  
Monoglyceride Lipase ◽  
Genetic Deficiency ◽  
Hormone Sensitive ◽  
Adipose Tissue Lipolysis ◽  
Hydrolysis Of

White adipose tissue (WAT) lipolysis contributes to energy balance during fasting. Lipolysis can proceed by the sequential hydrolysis of triglycerides (TGs) by adipose triglyceride lipase (ATGL), then of diacylglycerols (DGs) by hormone-sensitive lipase (HSL). We showed that the combined genetic deficiency of ATGL and HSL in mouse adipose tissue produces a striking different phenotype from that of isolated ATGL deficiency, inconsistent with the linear model of lipolysis. We hypothesized that the mechanism might be functional redundancy between ATGL and HSL. To test this, the TG hydrolase activity of HSL was measured in WAT. HSL showed TG hydrolase activity. Then, to test ATGL for activity towards DGs, radiolabeled DGs were incubated with HSL-deficient lipid droplet fractions. The content of TG increased, suggesting DG-to-TG synthesis rather than DG hydrolysis. TG synthesis was abolished by a specific ATGL inhibitor, suggesting that ATGL functions as a transacylase when HSL is deficient, transferring an acyl group from one DG to another, forming a TG plus a monoglyceride (MG) that could be hydrolyzed by monoglyceride lipase. These results reveal a previously unknown physiological redundancy between ATGL and HSL, a mechanism for the epistatic interaction between Pnpla2 and Lipe. It provides an alternative lipolytic pathway, potentially important in patients with deficient lipolysis.

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.

scholarly journals EFFECT OF MYOKINES ON THE QUANTITY OF HORMONE SENSITIVE LIPASE IN MSCS AND THE PRODUCTS OF THEIR ADIPOGENIC DIFFERENTIATION

2021 ◽  
Vol 10 (4) ◽  
pp. 29-35
Author(s):  
A. Mishra ◽  
E. V. Tsypandina ◽  
A. M. Gaponov ◽  
S. A. Rumyantsev ◽  
R. A. Khanferyan ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Skeletal Muscles ◽  
Adipogenic Differentiation ◽  
Hormone Sensitive Lipase ◽  
Adrenergic Agonist ◽  
Differentiation Protocol ◽  
Healthy Donors ◽  
Brown Adipose ◽  
Hormone Sensitive ◽  
Hydrolysis Of

The basic metabolic process associated with white and beige/brown adipose tissues is lipolysis – the sequential enzymatic process of the hydrolysis of triglycerides in the adipose tissue. It has been repeatedly shown that physical activity activates lipolysis. It has recently been shown that skeletal muscles have an endocrine role; producing a host of myogenic hormones – myokines. Current literature has an incomplete understanding of the interdependent relationship between skeletal muscles and adipose tissue. We researched the influence of myocyte secreted cytokines (myokines) – meteorin-like protein (METRNL) and β-aminoisobutyric acid (BAIBA), and the adrenergic agonist isoproterenol on the levels of total and phosphorylated (Ser552) hormone sensitive lipase (HSL) in adipose tissue derived mesenchymal stromal cells (MSCs) and the cellular products of their adipogenic differentiation. The MSCs were obtained from 5 healthy donors. The adipogenic differentiation protocol was carried out for a span of 21 days. After procuring the adipocyte cultures, the following stimulators were added – 5 μM METRNL, 5 μM BAIBA, and 5 μM isoproterenol. With the help of western blot, the change in the amount of total and activated levels of HSL were monitored in cells of three different adipogenic differentiation protocols in MSCs. We observed that HSL and its activated form are produced in cell cultures induced with factors for white, beige, and brown adipogenic differentiation.

scholarly journals Hydrolases (version 2019.5) in the IUPHAR/BPS Guide to Pharmacology Database

2019 ◽  
Vol 2019 (5) ◽  
Author(s):  
Stephen P.H. Alexander ◽  
Patrick Doherty ◽  
David Fairlie ◽  
Christopher J. Fowler ◽  
Christopher M. Overall ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Hormone Sensitive Lipase ◽  
High Density Lipoproteins ◽  
Endothelial Lipase ◽  
Monoacylglycerol Lipase ◽  
Fat Absorption ◽  
Fat Digestion ◽  
Hormone Sensitive ◽  
Concise Guide ◽  
Hydrolysis Of

Listed in this section are hydrolases not accumulated in other parts of the Concise Guide, such as monoacylglycerol lipase and acetylcholinesterase. Pancreatic lipase is the predominant mechanism of fat digestion in the alimentary system; its inhibition is associated with decreased fat absorption. CES1 is present at lower levels in the gut than CES2 (P23141), but predominates in the liver, where it is responsible for the hydrolysis of many aliphatic, aromatic and steroid esters. Hormone-sensitive lipase is also a relatively non-selective esterase associated with steroid ester hydrolysis and triglyceride metabolism, particularly in adipose tissue. Endothelial lipase is secreted from endothelial cells and regulates circulating cholesterol in high density lipoproteins.

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