title: G0/G1 Switch Gene 2 controls adipose triglyceride lipase activity and lipid metabolism in skeletal muscle.
abstract: OBJECTIVE
  Recent data suggest that adipose triglyceride lipase (ATGL) plays a key role in providing energy substrate from triglyceride pools and that alterations of its expression/activity relate to metabolic disturbances in skeletal muscle. Yet little is known about its regulation. We here investigated the role of the protein G0/G1 Switch Gene 2 (G0S2), recently described as an inhibitor of ATGL in white adipose tissue, in the regulation of lipolysis and oxidative metabolism in skeletal muscle.
  
  
  METHODS
  We first examined G0S2 protein expression in relation to metabolic status and muscle characteristics in humans. We next overexpressed and knocked down G0S2 in human primary myotubes to assess its impact on ATGL activity, lipid turnover and oxidative metabolism, and further knocked down G0S2 in vivo in mouse skeletal muscle.
  
  
  RESULTS
  G0S2 protein is increased in skeletal muscle of endurance-trained individuals and correlates with markers of oxidative capacity and lipid content. Recombinant G0S2 protein inhibits ATGL activity by about 40% in lysates of mouse and human skeletal muscle. G0S2 overexpression augments (+49%, p < 0.05) while G0S2 knockdown strongly reduces (-68%, p < 0.001) triglyceride content in human primary myotubes and mouse skeletal muscle. We further show that G0S2 controls lipolysis and fatty acid oxidation in a strictly ATGL-dependent manner. These metabolic adaptations mediated by G0S2 are paralleled by concomitant changes in glucose metabolism through the modulation of Pyruvate Dehydrogenase Kinase 4 (PDK4) expression (5.4 fold, p < 0.001). Importantly, downregulation of G0S2 in vivo in mouse skeletal muscle recapitulates changes in lipid metabolism observed in vitro.
  
  
  CONCLUSIONS
  Collectively, these data indicate that G0S2 plays a key role in the regulation of skeletal muscle ATGL activity, lipid content and oxidative metabolism.
authors.affiliation: INSERM, UMR1048, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France; University of Toulouse, Paul Sabatier University, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Laurens
authors.affiliation: INSERM, UMR1048, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France; University of Toulouse, Paul Sabatier University, France.
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Badin
authors.affiliation: INSERM, UMR1048, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France; University of Toulouse, Paul Sabatier University, France.
authors.forename: Katie
authors.initials: K
authors.lastname: Louche
authors.affiliation: INSERM, UMR1048, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France; University of Toulouse, Paul Sabatier University, France.
authors.forename: Aline
authors.initials: A
authors.lastname: Mairal
authors.affiliation: INSERM, UMR1048, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France; University of Toulouse, Paul Sabatier University, France.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Tavernier
authors.affiliation: Department of Medicine, Canada; Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Canada.
authors.forename: André
authors.initials: A
authors.lastname: Marette
authors.affiliation: Department of Kinesiology, Canada; Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Canada.
authors.forename: Angelo
authors.initials: A
authors.lastname: Tremblay
authors.affiliation: CHU-CHUQ, Laval University, Quebec City, Canada.
authors.forename: S John
authors.initials: SJ
authors.lastname: Weisnagel
authors.affiliation: Department of Kinesiology, Canada; Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Canada.
authors.forename: Denis R
authors.initials: DR
authors.lastname: Joanisse
authors.affiliation: INSERM, UMR1048, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France; University of Toulouse, Paul Sabatier University, France; Toulouse University Hospitals, Department of Clinical Biochemistry, Toulouse, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Langin
authors.affiliation: INSERM, UMR1048, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France; University of Toulouse, Paul Sabatier University, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Bourlier
authors.affiliation: INSERM, UMR1048, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France; University of Toulouse, Paul Sabatier University, France. Electronic address: Cedric.Moro@inserm.fr.
authors.forename: Cedric
authors.initials: C
authors.lastname: Moro
keywords: Adipose triglyceride lipase; Lipid metabolism; Lipolysis; Oxidative metabolism; Skeletal muscle