title: 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.
authors.affiliation: Inserm, 1048, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases, Paul Sabatier University, Toulouse, France.
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Badin
authors.affiliation: Inserm, 1048, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases, Paul Sabatier University, Toulouse, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Loubière
authors.affiliation: Inserm, 1048, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases, Paul Sabatier University, Toulouse, France.
authors.forename: Maarten
authors.initials: M
authors.lastname: Coonen
authors.affiliation: Inserm, 1048, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases, Paul Sabatier University, Toulouse, France.
authors.forename: Katie
authors.initials: K
authors.lastname: Louche
authors.affiliation: Inserm, 1048, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases, Paul Sabatier University, Toulouse, France.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Tavernier
authors.affiliation: Inserm, 1048, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases, Paul Sabatier University, Toulouse, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Bourlier
authors.affiliation: Inserm, 1048, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases, Paul Sabatier University, Toulouse, France.
authors.forename: Aline
authors.initials: A
authors.lastname: Mairal
authors.affiliation: Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway.
authors.forename: Arild C
authors.initials: AC
authors.lastname: Rustan
authors.affiliation: Translational Research Institute for Metabolism and Diabetes, Florida Hospital and the Burnham Institute for Medical Research, Winter Park, FL.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Smith
authors.affiliation: Inserm, 1048, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases, Paul Sabatier University, Toulouse, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Langin
authors.affiliation: Inserm, 1048, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases, Paul Sabatier University, Toulouse, France. Electronic address: Cedric.Moro@inserm.fr.
authors.forename: Cedric
authors.initials: C
authors.lastname: Moro
mesh_terms: D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000293:Adolescent; D000818:Animals; D002478:Cells, Cultured; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D055785:Gene Knockdown Techniques; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006867:Hydrolases / Q000378:metabolism; D008049:Lipase / Q000378:metabolism*; D008066:Lipolysis; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism*; D010084:Oxidation-Reduction; D047494:PPAR delta / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D055815:Young Adult
chemical_list: D005227:Fatty Acids; D047494:PPAR delta; D014280:Triglycerides; D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase; C439972:ABHD5 protein, human; D006867:Hydrolases; D008049:Lipase; D005947:Glucose