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Regulation of skeletal muscle lipolysis and oxidative metabolism by the co-lipase CGI-58.

Abstract : We investigated here the specific role of CGI-58 in the regulation of energy metabolism in skeletal muscle. We first examined CGI-58 protein expression in various muscle types in mice, and next modulated CGI-58 expression during overexpression and knockdown studies in human primary myotubes and evaluated the consequences on oxidative metabolism. We observed a preferential expression of CGI-58 in oxidative muscles in mice consistent with triacylglycerol hydrolase activity. We next showed by pulse-chase that CGI-58 overexpression increased by more than 2-fold the rate of triacylglycerol (TAG) hydrolysis, as well as TAG-derived fatty acid (FA) release and oxidation. Oppositely, CGI-58 silencing reduced TAG hydrolysis and TAG-derived FA release and oxidation (-77%, P < 0.001), whereas it increased glucose oxidation and glycogen synthesis. Interestingly, modulations of CGI-58 expression and FA release are reflected by changes in pyruvate dehydrogenase kinase 4 gene expression. This regulation involves the activation of the peroxisome proliferator activating receptor-δ (PPARδ) by lipolysis products. Altogether, these data reveal that CGI-58 plays a limiting role in the control of oxidative metabolism by modulating FA availability and the expression of PPARδ-target genes, and highlight an important metabolic function of CGI-58 in skeletal muscle.
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Contributor : Marie Francoise Simon Connect in order to contact the contributor
Submitted on : Thursday, August 30, 2012 - 2:35:24 PM
Last modification on : Wednesday, June 1, 2022 - 4:07:23 AM

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Pierre-Marie Badin, Camille Loubière, Maarten Coonen, Katie Louche, Geneviève Tavernier, et al.. Regulation of skeletal muscle lipolysis and oxidative metabolism by the co-lipase CGI-58.. Journal of Lipid Research, American Society for Biochemistry and Molecular Biology, 2012, 53 (5), pp.839-48. ⟨10.1194/jlr.M019182⟩. ⟨inserm-00726508⟩



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