title: Perilipin 5 fine-tunes lipid oxidation to metabolic demand and protects against lipotoxicity in skeletal muscle.
abstract: Lipid droplets (LD) play a central role in lipid homeostasis by controlling transient fatty acid (FA) storage and release from triacylglycerols stores, while preventing high levels of cellular toxic lipids. This crucial function in oxidative tissues is altered in obesity and type 2 diabetes. Perilipin 5 (PLIN5) is a LD protein whose mechanistic and causal link with lipotoxicity and insulin resistance has raised controversies. We investigated here the physiological role of PLIN5 in skeletal muscle upon various metabolic challenges. We show that PLIN5 protein is elevated in endurance-trained (ET) subjects and correlates with muscle oxidative capacity and whole-body insulin sensitivity. When overexpressed in human skeletal muscle cells to recapitulate the ET phenotype, PLIN5 diminishes lipolysis and FA oxidation under basal condition, but paradoxically enhances FA oxidation during forskolin- and contraction- mediated lipolysis. Moreover, PLIN5 partly protects muscle cells against lipid-induced lipotoxicity. In addition, we demonstrate that down-regulation of PLIN5 in skeletal muscle inhibits insulin-mediated glucose uptake under normal chow feeding condition, while paradoxically improving insulin sensitivity upon high-fat feeding. These data highlight a key role of PLIN5 in LD function, first by finely adjusting LD FA supply to mitochondrial oxidation, and second acting as a protective factor against lipotoxicity in skeletal muscle.
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: 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.
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: 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: 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: Etienne
authors.initials: E
authors.lastname: Mouisel
authors.affiliation: University of Toulouse, Paul Sabatier University, France.|INRA, UMR 1331, TOXALIM, Toulouse, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Montagner
authors.affiliation: Department of Medicine, Laval University, Quebec City, Canada.|Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Laval University, Quebec City, Canada.
authors.forename: André
authors.initials: A
authors.lastname: Marette
authors.affiliation: Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Laval University, Quebec City, Canada.|Department of Kinesiology, Laval University, Quebec City, Canada.
authors.forename: Angelo
authors.initials: A
authors.lastname: Tremblay
authors.affiliation: CHU-CHUQ, Laval University, Quebec City, Canada.
authors.forename: John S
authors.initials: JS
authors.lastname: Weisnagel
authors.affiliation: University of Toulouse, Paul Sabatier University, France.|INRA, UMR 1331, TOXALIM, Toulouse, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Guillou
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: Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Laval University, Quebec City, Canada.|Department of Kinesiology, Laval University, Quebec City, 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.
authors.forename: Cedric
authors.initials: C
authors.lastname: Moro
mesh_terms: D000818:Animals; D001835:Body Weight; D004075:Diglycerides / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007333:Insulin Resistance; D066292:Lipid Droplets / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D019301:Oleic Acid / Q000378:metabolism / Q000494:pharmacology; D010084:Oxidation-Reduction; D000070797:Perilipin-5 / Q000235:genetics* / Q000378:metabolism; D010807:Physical Endurance / Q000502:physiology; D061251:Primary Cell Culture; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D057185:Sedentary Behavior; D014280:Triglycerides / Q000378:metabolism
chemical_list: D004075:Diglycerides; C544352:PLIN5 protein, human; D000070797:Perilipin-5; C511805:Plin5 protein, mouse; D014280:Triglycerides; D019301:Oleic Acid