| First Author | Badin PM | Year | 2012 |
| Journal | J Lipid Res | Volume | 53 |
| Issue | 5 | Pages | 839-48 |
| PubMed ID | 22383684 | Mgi Jnum | J:184917 |
| Mgi Id | MGI:5426736 | Doi | 10.1194/jlr.M019182 |
| Citation | Badin PM, et al. (2012) Regulation of skeletal muscle lipolysis and oxidative metabolism by the co-lipase CGI-58. J Lipid Res 53(5):839-48 |
| abstractText | 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-delta (PPARdelta) 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 PPARdelta-target genes, and highlight an important metabolic function of CGI-58 in skeletal muscle. |
