G0/G1 Switch Gene 2 Regulates Cardiac Lipolysis.

Autor:	Heier C; From the Institute of Molecular Biosciences, University of Graz, A-8010 Graz, Austria., Radner FP; From the Institute of Molecular Biosciences, University of Graz, A-8010 Graz, Austria., Moustafa T; From the Institute of Molecular Biosciences, University of Graz, A-8010 Graz, Austria, the Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine and., Schreiber R; From the Institute of Molecular Biosciences, University of Graz, A-8010 Graz, Austria., Grond S; From the Institute of Molecular Biosciences, University of Graz, A-8010 Graz, Austria., Eichmann TO; From the Institute of Molecular Biosciences, University of Graz, A-8010 Graz, Austria., Schweiger M; From the Institute of Molecular Biosciences, University of Graz, A-8010 Graz, Austria., Schmidt A; Division of Cardiology, Department of Internal Medicine, Medical University of Graz, A-8036 Graz, Austria, and., Cerk IK; From the Institute of Molecular Biosciences, University of Graz, A-8010 Graz, Austria., Oberer M; From the Institute of Molecular Biosciences, University of Graz, A-8010 Graz, Austria., Theussl HC; the Transgenic Service, Research Institute of Molecular Pathology (IMP), 1030 Vienna, Austria, and the IMBA Institute of Molecular Biotechnology of the Austrian Academy of Sciences, 1030 Vienna, Austria., Wojciechowski J; the Transgenic Service, Research Institute of Molecular Pathology (IMP), 1030 Vienna, Austria, and the IMBA Institute of Molecular Biotechnology of the Austrian Academy of Sciences, 1030 Vienna, Austria., Penninger JM; the Transgenic Service, Research Institute of Molecular Pathology (IMP), 1030 Vienna, Austria, and the IMBA Institute of Molecular Biotechnology of the Austrian Academy of Sciences, 1030 Vienna, Austria., Zimmermann R; From the Institute of Molecular Biosciences, University of Graz, A-8010 Graz, Austria., Zechner R; From the Institute of Molecular Biosciences, University of Graz, A-8010 Graz, Austria, rudolf.zechner@uni-graz.at.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2015 Oct 23; Vol. 290 (43), pp. 26141-50. Date of Electronic Publication: 2015 Sep 08.
DOI:	10.1074/jbc.M115.671842
Abstrakt:	The anabolism and catabolism of myocardial triacylglycerol (TAG) stores are important processes for normal cardiac function. TAG synthesis detoxifies and stockpiles fatty acids to prevent lipotoxicity, whereas TAG hydrolysis (lipolysis) remobilizes fatty acids from endogenous storage pools as energy substrates, signaling molecules, or precursors for complex lipids. This study focused on the role of G0/G1 switch 2 (G0S2) protein, which was previously shown to inhibit the principal TAG hydrolase adipose triglyceride lipase (ATGL), in the regulation of cardiac lipolysis. Using wild-type and mutant mice, we show the following: (i) G0S2 is expressed in the heart and regulated by the nutritional status with highest expression levels after re-feeding. (ii) Cardiac-specific overexpression of G0S2 inhibits cardiac lipolysis by direct protein-protein interaction with ATGL. This leads to severe cardiac steatosis. The steatotic hearts caused by G0S2 overexpression are less prone to fibrotic remodeling or cardiac dysfunction than hearts with a lipolytic defect due to ATGL deficiency. (iii) Conversely to the phenotype of transgenic mice, G0S2 deficiency results in a de-repression of cardiac lipolysis and decreased cardiac TAG content. We conclude that G0S2 acts as a potent ATGL inhibitor in the heart modulating cardiac substrate utilization by regulating cardiac lipolysis. (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.)
Databáze:	MEDLINE
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