G0/G1 Switch Gene 2 controls adipose triglyceride lipase activity and lipid metabolism in skeletal muscle
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 investi...
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Format: | Article |
Language: | English |
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Elsevier
2016-07-01
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Series: | Molecular Metabolism |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2212877816300217 |
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doaj-733711b7f0b04ae3ba2a921482a6034d |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Claire Laurens Pierre-Marie Badin Katie Louche Aline Mairal Geneviève Tavernier André Marette Angelo Tremblay S. John Weisnagel Denis R. Joanisse Dominique Langin Virginie Bourlier Cedric Moro |
spellingShingle |
Claire Laurens Pierre-Marie Badin Katie Louche Aline Mairal Geneviève Tavernier André Marette Angelo Tremblay S. John Weisnagel Denis R. Joanisse Dominique Langin Virginie Bourlier Cedric Moro G0/G1 Switch Gene 2 controls adipose triglyceride lipase activity and lipid metabolism in skeletal muscle Molecular Metabolism |
author_facet |
Claire Laurens Pierre-Marie Badin Katie Louche Aline Mairal Geneviève Tavernier André Marette Angelo Tremblay S. John Weisnagel Denis R. Joanisse Dominique Langin Virginie Bourlier Cedric Moro |
author_sort |
Claire Laurens |
title |
G0/G1 Switch Gene 2 controls adipose triglyceride lipase activity and lipid metabolism in skeletal muscle |
title_short |
G0/G1 Switch Gene 2 controls adipose triglyceride lipase activity and lipid metabolism in skeletal muscle |
title_full |
G0/G1 Switch Gene 2 controls adipose triglyceride lipase activity and lipid metabolism in skeletal muscle |
title_fullStr |
G0/G1 Switch Gene 2 controls adipose triglyceride lipase activity and lipid metabolism in skeletal muscle |
title_full_unstemmed |
G0/G1 Switch Gene 2 controls adipose triglyceride lipase activity and lipid metabolism in skeletal muscle |
title_sort |
g0/g1 switch gene 2 controls adipose triglyceride lipase activity and lipid metabolism in skeletal muscle |
publisher |
Elsevier |
series |
Molecular Metabolism |
issn |
2212-8778 |
publishDate |
2016-07-01 |
description |
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. Conclusion: Collectively, these data indicate that G0S2 plays a key role in the regulation of skeletal muscle ATGL activity, lipid content and oxidative metabolism. Keywords: Lipid metabolism, Skeletal muscle, Lipolysis, Adipose triglyceride lipase, Oxidative metabolism |
url |
http://www.sciencedirect.com/science/article/pii/S2212877816300217 |
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doaj-733711b7f0b04ae3ba2a921482a6034d2020-11-25T00:24:15ZengElsevierMolecular Metabolism2212-87782016-07-0157527537G0/G1 Switch Gene 2 controls adipose triglyceride lipase activity and lipid metabolism in skeletal muscleClaire Laurens0Pierre-Marie Badin1Katie Louche2Aline Mairal3Geneviève Tavernier4André Marette5Angelo Tremblay6S. John Weisnagel7Denis R. Joanisse8Dominique Langin9Virginie Bourlier10Cedric Moro11INSERM, UMR1048, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France; University of Toulouse, Paul Sabatier University, FranceINSERM, UMR1048, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France; University of Toulouse, Paul Sabatier University, FranceINSERM, UMR1048, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France; University of Toulouse, Paul Sabatier University, FranceINSERM, UMR1048, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France; University of Toulouse, Paul Sabatier University, FranceINSERM, UMR1048, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France; University of Toulouse, Paul Sabatier University, FranceDepartment of Medicine, Canada; Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, CanadaDepartment of Kinesiology, Canada; Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, CanadaCHU-CHUQ, Laval University, Quebec City, CanadaDepartment of Kinesiology, Canada; Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, CanadaINSERM, UMR1048, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France; University of Toulouse, Paul Sabatier University, France; Toulouse University Hospitals, Department of Clinical Biochemistry, Toulouse, FranceINSERM, UMR1048, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France; University of Toulouse, Paul Sabatier University, FranceINSERM, UMR1048, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France; University of Toulouse, Paul Sabatier University, France; Corresponding author. Inserm UMR1048, Institute of Metabolic and Cardiovascular Diseases, CHU Rangueil, BP84225, 1 avenue Jean Poulhès, 31432, Toulouse cedex 4, France. Tel.: +33 561 32 5626; fax: +33 561 32 5623.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. Conclusion: Collectively, these data indicate that G0S2 plays a key role in the regulation of skeletal muscle ATGL activity, lipid content and oxidative metabolism. Keywords: Lipid metabolism, Skeletal muscle, Lipolysis, Adipose triglyceride lipase, Oxidative metabolismhttp://www.sciencedirect.com/science/article/pii/S2212877816300217 |