G0/G1 Switch Gene 2 controls adipose triglyceride lipase activity and lipid metabolism in skeletal muscle

The role of carboxylesterase 3 (Ces3) in the lipolysis of adipocytes has been overlooked, as 2 major lipolytic enzymes, hormone-sensitive lipase and adipose triglyceride lipase, play more powerful roles in lipolysis. In this study, we explored the effects of Ces3 in lipid metabolism by activating and inhibiting, as well as silencing, Ces3-encoding gene in 3T3-L1 cell model. Our results demonstrated that activation of Ces3 increased adipogenesis, and attenuated lipogenesis, whereas it promoted lipolysis and fatty acid oxidation. In addition, activated Ces3 led to enhanced expression of core fat browning marker genes and proteins, suggesting that Ces3 may play a pivotal role in fat browning and thermogenesis. In contrast, deficiency of Ces3 nullified the browning effect in white adipocytes, along with decreased adipogenesis in 3T3-L1 adipocytes. Interestingly, the expression pattern of adipose triglyceride lipase was in line with Ces3, whereas hormone-sensitive lipase was independently regulated irrespective of Ces3 expression levels, suggesting that Ces3 may play an important and compensatory role in the breakdown of triglycerides in white adipocytes. In conclusion, we provide the first evidence that activation of Ces3 contributes in the browning of white adipocytes, and maintains a balance in lipid metabolism, which could be a potential strategy in fighting against obesity.

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Palmitic acid follows a different metabolic pathway than oleic acid in human skeletal muscle cells; lower lipolysis rate despite an increased level of adipose triglyceride lipase

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids ◽

10.1016/j.bbalip.2012.07.001 ◽

2012 ◽

Vol 1821 (10) ◽

pp. 1323-1333 ◽

Cited By ~ 17

Author(s):

Siril S. Bakke ◽

Cedric Moro ◽

Nataša Nikolić ◽

Nina P. Hessvik ◽

Pierre-Marie Badin ◽

...

Keyword(s):

Skeletal Muscle ◽

Oleic Acid ◽

Palmitic Acid ◽

Metabolic Pathway ◽

Human Skeletal Muscle ◽

Muscle Cells ◽

Skeletal Muscle Cells ◽

Adipose Triglyceride Lipase ◽

Triglyceride Lipase ◽

Human Skeletal Muscle Cells

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PPARγ regulates adipose triglyceride lipase in adipocytes in vitro and in vivo

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00122.2007 ◽

2007 ◽

Vol 293 (6) ◽

pp. E1736-E1745 ◽

Cited By ~ 132

Author(s):

Erin E. Kershaw ◽

Michael Schupp ◽

Hong-Ping Guan ◽

Noah P. Gardner ◽

Mitchell A. Lazar ◽

...

Keyword(s):

Protein Synthesis ◽

Adipose Tissue ◽

Lipid Metabolism ◽

Protein Synthesis Inhibitor ◽

Adipose Triglyceride Lipase ◽

Dependent Manner ◽

Triglyceride Lipase ◽

Brown Adipose

Peroxisome proliferator-activated receptor-γ (PPARγ) regulates adipocyte genes involved in adipogenesis and lipid metabolism and is the molecular target for thiazolidinedione (TZD) antidiabetic agents. Adipose triglyceride lipase (ATGL) is a recently described triglyceride-specific lipase that is induced during adipogenesis and remains highly expressed in mature adipocytes. This study evaluates the ability of PPARγ to directly regulate ATGL expression in adipocytes in vitro and in vivo. In fully differentiated 3T3-L1 adipocytes, ATGL mRNA and protein are increased by TZD and non-TZD PPARγ agonists in a dose- and time-dependent manner. Rosiglitazone-mediated induction of ATGL mRNA is rapid and is not inhibited by the protein synthesis inhibitor cycloheximide, indicating that intervening protein synthesis is not required for this effect. Rosiglitazone-mediated induction of ATGL mRNA and protein is inhibited by the PPARγ-specific antagonist GW-9662 and is also significantly reduced following siRNA-mediated knockdown of PPARγ, supporting the direct transcriptional regulation of ATGL by PPARγ. In vivo, ATGL mRNA and protein are increased by rosiglitazone treatment in white and brown adipose tissue of mice with and without obesity due to high-fat diet or leptin deficiency. Thus, PPARγ positively regulates ATGL mRNA and protein expression in mature adipocytes in vitro and in adipose tissue in vivo, suggesting a role for ATGL in mediating PPARγ's effects on lipid metabolism.

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Distinct roles for α-β hydrolase domain 5 (ABHD5/CGI-58) and adipose triglyceride lipase (ATGL/PNPLA2) in lipid metabolism and signaling

Adipocyte ◽

10.4161/adip.20035 ◽

2012 ◽

Vol 1 (3) ◽

pp. 123-131 ◽

Cited By ~ 21

Author(s):

Caleb C. Lord ◽

J. Mark Brown

Keyword(s):

Lipid Metabolism ◽

Adipose Triglyceride Lipase ◽

Triglyceride Lipase

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Adipose triglyceride lipase (ATGL) expression in human skeletal muscle is type I (oxidative) fiber specific

Histochemistry and Cell Biology ◽

10.1007/s00418-008-0386-y ◽

2008 ◽

Vol 129 (4) ◽

pp. 535-538 ◽

Cited By ~ 46

Author(s):

Johan W. E. Jocken ◽

Egbert Smit ◽

Gijs H. Goossens ◽

Yvonne P. G. Essers ◽

Marleen A. Baak ◽

...

Keyword(s):

Skeletal Muscle ◽

Human Skeletal Muscle ◽

Adipose Triglyceride Lipase ◽

Type I ◽

Triglyceride Lipase

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Adipose triglyceride lipase in human skeletal muscle is upregulated by exercise training

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.90912.2008 ◽

2009 ◽

Vol 296 (3) ◽

pp. E445-E453 ◽

Cited By ~ 93

Author(s):

Thomas J. Alsted ◽

Lars Nybo ◽

Martina Schweiger ◽

Christian Fledelius ◽

Poul Jacobsen ◽

...

Keyword(s):

Skeletal Muscle ◽

Exercise Training ◽

Endurance Exercise ◽

Human Skeletal Muscle ◽

Hormone Sensitive Lipase ◽

Adipose Triglyceride Lipase ◽

Skeletal Muscle Biopsy ◽

Triglyceride Lipase ◽

Endurance Exercise Training ◽

Molecule Inhibitor

Mobilization of fatty acids from stored triacylglycerol (TG) in adipose tissue and skeletal muscle [intramyocellular triacylglycerol (IMTG)] requires activity of lipases. Although exercise training increases the lipolytic capacity of skeletal muscle, the expression of hormone-sensitive lipase (HSL) is not changed. Recently, adipose triglyceride lipase (ATGL) was identified as a TG-specific lipase in various rodent tissues. To investigate whether human skeletal muscle ATGL protein is regulated by endurance exercise training, 10 healthy young men completed 8 wk of supervised endurance exercise training. Western blotting analysis on lysates of skeletal muscle biopsy samples revealed that exercise training induced a twofold increase in skeletal muscle ATGL protein content. In contrast to ATGL, expression of comparative gene identification 58 (CGI-58), the activating protein of ATGL, and HSL protein was not significantly changed after the training period. The IMTG concentration was significantly decreased by 28% at termination of the training program compared with before. HSL-phoshorylation at Ser660 was increased, HSL-Ser659 phosporylation was unchanged, and HSL-phoshorylation at Ser565 was decreased altogether, indicating an enhanced basal activity of this lipase. No change was found in the expression of diacylglycerol acyl transferase 1 (DGAT1) after training. Inhibition of HSL with a monospecific, small molecule inhibitor (76-0079) and stimulation of ATGL with CGI-58 revealed that significant ATGL activity is present in human skeletal muscle. These results suggest that ATGL in addition to HSL may be important for human skeletal muscle lipolysis.

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Characterization of the triacylglycerol lipase activity in three types of rat skeletal muscle

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y87-055 ◽

1987 ◽

Vol 65 (3) ◽

pp. 317-322 ◽

Cited By ~ 7

Author(s):

Wayne C. Miller ◽

Warren K. Palmer ◽

David A. Arnall ◽

Lawrence B. Oscai

Keyword(s):

Skeletal Muscle ◽

Lipoprotein Lipase ◽

Lipase Activity ◽

Lipolytic Activity ◽

Vastus Lateralis ◽

High Energy ◽

Glycolytic Flux ◽

Ph Optimum ◽

Triacylglycerol Lipase ◽

Triglyceride Lipase

The purpose of this study was to characterize the lipolytic activity of the alkaline triglyceride lipase in homogenates of three types of skeletal muscle obtained from heparin-perfused rat hindlimb. Specifically, the red portion of the vastus lateralis, the white portion of the vastus lateralis, and the soleus muscles were examined. To remove capillary-bound lipoprotein lipase from the capillary beds, muscle was perfused with an erythrocyte-free buffer containing 4% albumin, 5 units of heparin/mL, and 7.5 μM adenosine. Adenosine reduced perfusion pressure from 117 ± 5 to 86 ± 6 mmHg (1 mmHg = 133.32 Pa), providing evidence for an effective vasodilation. This vasodilation increased the amount of lipoprotein lipase removed from the capillary beds. By the end of the experiment, perfusates were lipoprotein lipase-free. Oxygen supply to the perfused hindlimb appeared adequate as evidenced by similar high energy phosphate values for perfused and contralateral control tissues. For example, in soleus muscle, ATP content was 4.5 ± 0.6 vs. 4.2 ± 0.3 μmol/g, ADP concentration was 1.0 ± 0.2 vs. 1.4 ± 0.2 μmol/g, and creatine phosphate level was 12.9 ± 0.7 vs. 11.0 ± 0.6 μmol/g for perfused and contralateral control soleus, respectively. In addition, K+ output by the hindlimb was negligible, while glycolytic flux of perfused muscle was similar to that measured in control tissue. The findings that triglyceride levels of soleus and red vastus lateralis were decreased suggest that endogenous triglyceride was providing energy for the hindlimb during perfusion. Skeletal muscle triglyceride lipase activity was stimulated by serum and heparin, inhibited by NaCl and protamine, and had a pH optimum of 8.1. These results are consistent with the hypothesis that the major lipolytic activity present in the intracellular compartment of skeletal muscle is the alkaline triglyceride lipase with characteristics similar to those of lipoprotein lipase.

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