G0/G1 Switch Gene 2 Regulates Cardiac Lipolysis.
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.
From the Institute of Molecular Biosciences, University of Graz, A-8010 Graz, Austria.
Christoph
C
Heier
From the Institute of Molecular Biosciences, University of Graz, A-8010 Graz, Austria.
Franz P W
FP
Radner
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.
Tarek
T
Moustafa
From the Institute of Molecular Biosciences, University of Graz, A-8010 Graz, Austria.
Renate
R
Schreiber
From the Institute of Molecular Biosciences, University of Graz, A-8010 Graz, Austria.
Susanne
S
Grond
From the Institute of Molecular Biosciences, University of Graz, A-8010 Graz, Austria.
Thomas O
TO
Eichmann
From the Institute of Molecular Biosciences, University of Graz, A-8010 Graz, Austria.
Martina
M
Schweiger
Division of Cardiology, Department of Internal Medicine, Medical University of Graz, A-8036 Graz, Austria, and.
Albrecht
A
Schmidt
From the Institute of Molecular Biosciences, University of Graz, A-8010 Graz, Austria.
Ines K
IK
Cerk
From the Institute of Molecular Biosciences, University of Graz, A-8010 Graz, Austria.
Monika
M
Oberer
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.
H-Christian
HC
Theussl
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.
Jacek
J
Wojciechowski
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.
Josef M
JM
Penninger
From the Institute of Molecular Biosciences, University of Graz, A-8010 Graz, Austria.
Robert
R
Zimmermann
From the Institute of Molecular Biosciences, University of Graz, A-8010 Graz, Austria, rudolf.zechner@uni-graz.at.
Rudolf
R
Zechner
D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics*; D002460:Cell Line; D016193:G1 Phase / Q000235:genetics*; D006334:Heart Function Tests; D008066:Lipolysis / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism*; D016192:Resting Phase, Cell Cycle / Q000235:genetics*; D014280:Triglycerides / Q000378:metabolism*
D018797:Cell Cycle Proteins; C508072:G0S2 protein, mouse; D014280:Triglycerides
G0S2; adipose triglyceride lipase (ATGL); cardiac lipid metabolism; cardiac metabolism; lipid metabolism; lipolysis; triacylglycerol