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

International Collaboration

cited authors

  • Badin, Pierre-Marie, Loubiere, Camille, Coonen, Maarten, Louche, Katie, Tavernier, Genevieve, Bourlier, Virginie, Mairal, Aline, Rustan, Arild C., Smith, Steven R., Langin, Dominique, Moro, Cedric

funding text

  • This study was supported by grants from the National Research Agency ANR-09-JCJC-0019-01 and from the European Federation for the Study of Diabetes/Novo Nordisk (C.M.); the Commission of the European Communities (Integrated Project HEPADIP (http://www.hepadip.org/), Contract LSHM-CT-2005-018734 (D.L.); and the National Insitutes of Health US 1P30 DK072476 (Pennington Biomedical Research Center/Nutrition Obesity Research Center) and R01AG030226 (S.R.S.). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health or other granting agencies.

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-delta (PPAR delta) by lipolysis products.jlr 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 PPAR delta-target genes, and highlight an important metabolic function of CGI-58 in skeletal muscle.-Badin, P-M., C. Loubiere, M. Coonen, K. Louche, G. Tavernier, V. Bourlier, A. Mairal, A. C. Rustan, S. R. Smith, D. Langin, and C. Moro. Regulation of skeletal muscle lipolysis and oxidative metabolism by the co-lipase CGI-58. J. Lipid Res. 2012. 53: 839-848.

authors

Publication Date

  • May 1, 2012

webpage

published in

category

start page

  • 839

end page

  • 848

volume

  • 53

issue

  • 5

WoS Citations

  • 35

WoS References

  • 42