1. G0/G1 switch gene-2 regulates human adipocyte lipolysis by affecting activity and localization of adipose triglyceride lipase
- Author
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Ines K. Cerk, Robert Zimmermann, Franz P.W. Radner, Susanne Grond, Irina Cornaciu, Martina Schweiger, Monika Oberer, Elena Moser, Gregor Gorkiewicz, Sander Kersten, Janina Brandis, Achim Lass, Margret Paar, Christina Eder, and Rudolf Zechner
- Subjects
Cellular differentiation ,Adipose tissue ,Cell Cycle Proteins ,Hormone-sensitive lipase ,Biochemistry ,triacylglycerol catabolism ,Mice ,chemistry.chemical_compound ,Voeding, Metabolisme en Genomica ,Endocrinology ,Lipid droplet ,Adipocyte ,insulin resistance ,Adipocytes ,Cells, Cultured ,Research Articles ,Cell Differentiation ,regulation ,Metabolism and Genomics ,Cysteine Endopeptidases ,hormone-sensitive lipase ,messenger-rna ,Metabolisme en Genomica ,comparative gene identification-58 ,Nutrition, Metabolism and Genomics ,medicine.medical_specialty ,Lipolysis ,Immunoblotting ,QD415-436 ,In Vitro Techniques ,Biology ,Voeding ,Downregulation and upregulation ,3T3-L1 Cells ,Internal medicine ,cgi-58 ,medicine ,Animals ,Humans ,human lipolysis ,Nutrition ,VLAG ,Global Nutrition ,Wereldvoeding ,disease ,2 g0s2 ,tissue ,Lipase ,Cell Biology ,Mice, Inbred C57BL ,Microscopy, Fluorescence ,chemistry ,Adipose triglyceride lipase ,Mutagenesis, Site-Directed ,chanarin-dorfman-syndrome ,protein ,lysophosphatidic acid - Abstract
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.
- Published
- 2012