G0/G1 switch gene-2 regulates human adipocyte lipolysis by affecting activity and localization of adipose triglyceride lipase.
The hydrolysis of triglycerides in adipocytes, termed lipolysis, provides free fatty acids as energy fuel. Murine lipolysis largely depends on the activity of adipose triglyceride lipase (ATGL), which is regulated by two proteins annotated as comparative gene identification-58 (CGI-58) and G0/G1 switch gene-2 (G0S2). CGI-58 activates and G0S2 inhibits ATGL activity. In contrast to mice, the functional role of G0S2 in human adipocyte lipolysis is poorly characterized. Here we show that overexpression or silencing of G0S2 in human SGBS adipocytes decreases and increases lipolysis, respectively. Human G0S2 is upregulated during adipocyte differentiation and inhibits ATGL activity in a dose-dependent manner. Interestingly, C-terminally truncated ATGL mutants, which fail to localize to lipid droplets, translocate to the lipid droplet upon coexpression with G0S2, suggesting that G0S2 anchors ATGL to lipid droplets independent of ATGL's C-terminal lipid binding domain. Taken together, our results indicate that G0S2 also regulates human lipolysis by affecting enzyme activity and intracellular localization of ATGL. Increased lipolysis is known to contribute to the pathogenesis of insulin resistance, and G0S2 expression has been shown to be reduced in poorly controlled type 2 diabetic patients. Our data indicate that downregulation of G0S2 in adipose tissue could represent one of the underlying causes leading to increased lipolysis in the insulin-resistant state.
Institute of Molecular Biosciences  University of Graz, 8010 Graz,  Austria.
Martina
M
Schweiger
Margret
M
Paar
Christina
C
Eder
Janina
J
Brandis
Elena
E
Moser
Gregor
G
Gorkiewicz
Susanne
S
Grond
Franz P W
FP
Radner
Ines
I
Cerk
Irina
I
Cornaciu
Monika
M
Oberer
Sander
S
Kersten
Rudolf
R
Zechner
Robert
R
Zimmermann
Achim
A
Lass
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D066298:In Vitro Techniques; D008049:Lipase / Q000235:genetics / Q000378:metabolism*; D008066:Lipolysis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D016297:Mutagenesis, Site-Directed; D000217:Acyltransferases
D018797:Cell Cycle Proteins; D003546:Cysteine Endopeptidases; D008049:Lipase; C508073:G0S2 protein, human; C508072:G0S2 protein, mouse; C494794:PNPLA2 protein, human; D000217:Acyltransferases; C056657:cysteine proteinase I