title: The G(0)/G(1) switch gene 2 regulates adipose lipolysis through association with adipose triglyceride lipase.
abstract: Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme for triacylglycerol (TAG) hydrolysis in adipocytes. The precise mechanisms whereby ATGL is regulated remain uncertain. Here, we demonstrate that a protein encoded by G(0)/G(1) switch gene 2 (G0S2) is a selective regulator of ATGL. G0S2 is highly expressed in adipose tissue and differentiated adipocytes. When overexpressed in HeLa cells, G0S2 localizes to lipid droplets and prevents their degradation mediated by ATGL. Moreover, G0S2 specifically interacts with ATGL through the hydrophobic domain of G0S2 and the patatin-like domain of ATGL. More importantly, interaction with G0S2 inhibits ATGL TAG hydrolase activity. Knockdown of endogenous G0S2 accelerates basal and stimulated lipolysis in adipocytes, whereas overexpression of G0S2 diminishes the rate of lipolysis in both adipocytes and adipose tissue explants. Thus, G0S2 functions to attenuate ATGL action both in vitro and in vivo and by this mechanism regulates TAG hydrolysis.
authors.affiliation: Department of Pediatrics, University of Kentucky, Lexington, USA.
authors.forename: Xingyuan
authors.initials: X
authors.lastname: Yang
authors.forename: Xin
authors.initials: X
authors.lastname: Lu
authors.forename: Marc
authors.initials: M
authors.lastname: Lombès
authors.forename: Geun Bae
authors.initials: GB
authors.lastname: Rha
authors.forename: Young-In
authors.initials: YI
authors.lastname: Chi
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Guerin
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Smart
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
mesh_terms: D017667:Adipocytes / Q000201:enzymology* / Q000648:ultrastructure; D000273:Adipose Tissue / Q000201:enzymology*; D000818:Animals; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D008049:Lipase / Q000378:metabolism*; D008055:Lipids; D008066:Lipolysis / Q000235:genetics*; D051379:Mice; D054730:Protein Interaction Domains and Motifs; D014617:Vacuoles / Q000378:metabolism; D000217:Acyltransferases
chemical_list: D002265:Carboxylic Ester Hydrolases; D018797:Cell Cycle Proteins; D008049:Lipase; D008055:Lipids; C508072:G0S2 protein, mouse; C494794:PNPLA2 protein, human; D000217:Acyltransferases; C494445:PNPLA2 protein, mouse