Document Detail


Regulation of skeletal muscle lipolysis and oxidative metabolism by the co-lipase CGI-58.
MedLine Citation:
PMID:  22383684     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Pierre-Marie Badin; Camille Loubière; Maarten Coonen; Katie Louche; Geneviève Tavernier; Virginie Bourlier; Aline Mairal; Arild C Rustan; Steven R Smith; Dominique Langin; Cedric Moro
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-02-29
Journal Detail:
Title:  Journal of lipid research     Volume:  53     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-04-12     Completed Date:  2012-08-08     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  839-48     Citation Subset:  IM    
Affiliation:
Inserm 1048, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases, Paul Sabatier University, Toulouse, France.
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MeSH Terms
Descriptor/Qualifier:
1-Acylglycerol-3-Phosphate O-Acyltransferase / deficiency,  genetics,  metabolism*
Adolescent
Animals
Cells, Cultured
Energy Metabolism*
Fatty Acids / metabolism
Gene Expression Regulation, Enzymologic
Gene Knockdown Techniques
Glucose / metabolism
Humans
Hydrolases / metabolism
Lipase / metabolism*
Lipolysis*
Mice
Mitochondria / metabolism
Muscle Fibers, Skeletal / cytology,  metabolism
Muscle, Skeletal / enzymology,  metabolism*
Oxidation-Reduction
PPAR delta / metabolism
Triglycerides / metabolism
Young Adult
Grant Support
ID/Acronym/Agency:
1P30 DK072476/DK/NIDDK NIH HHS; R01AG030226/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
0/Fatty Acids; 0/PPAR delta; 0/Triglycerides; 50-99-7/Glucose; EC 2.3.1.51/1-Acylglycerol-3-Phosphate O-Acyltransferase; EC 2.3.1.51/ABHD5 protein, human; EC 3.-/Hydrolases; EC 3.1.1.3/Lipase
Comments/Corrections

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