title: Increasing mitochondrial muscle fatty acid oxidation induces skeletal muscle remodeling toward an oxidative phenotype.
abstract: Adult skeletal muscle is a dynamic, remarkably plastic tissue, which allows myofibers to switch from fast/glycolytic to slow/oxidative types and to increase mitochondrial fatty acid oxidation (mFAO) capacity and vascularization in response to exercise training. mFAO is the main muscle energy source during endurance exercise, with carnitine palmitoyltransferase 1 (CPT1) being the key regulatory enzyme. Whether increasing muscle mFAO affects skeletal muscle physiology in adulthood actually remains unknown. To investigate this, we used in vivo electrotransfer technology to express in mouse tibialis anterior (TA), a fast/glycolytic muscle, a mutated CPT1 form (CPT1mt) that is active but insensitive to malonyl-CoA, its physiologic inhibitor. In young (2-mo-old) adult mice, muscle CPT1mt expression enhanced mFAO (+40%), but also increased the percentage of oxidative fibers (+28%), glycogen content, and capillary-to-fiber density (+45%). This CPT1mt-induced muscle remodeling, which mimicked exercise-induced oxidative phenotype, led to a greater resistance to muscle fatigue. In the context of aging, characterized by sarcopenia and reduced oxidative capacity, CPT1mt expression in TAs from aged (20-mo-old) mice partially reversed aging-associated sarcopenia and fiber-type transition, and increased muscle capillarity. These findings provide evidence that mFAO regulates muscle phenotype and may be a potential target to combat age-related decline in muscle function.
authors.affiliation: *Institut National de la Santé et de la Recherche Médicale (INSERM), U1016, Institut Cochin, Paris, France; Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche (UMR) 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; and INSERM U974, CNRS UMR 7215, Université Pierre et Marie Curie UMRS 974, Institut de Myologie, Paris, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Hénique
authors.affiliation: *Institut National de la Santé et de la Recherche Médicale (INSERM), U1016, Institut Cochin, Paris, France; Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche (UMR) 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; and INSERM U974, CNRS UMR 7215, Université Pierre et Marie Curie UMRS 974, Institut de Myologie, Paris, France.
authors.forename: Abdelhak
authors.initials: A
authors.lastname: Mansouri
authors.affiliation: *Institut National de la Santé et de la Recherche Médicale (INSERM), U1016, Institut Cochin, Paris, France; Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche (UMR) 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; and INSERM U974, CNRS UMR 7215, Université Pierre et Marie Curie UMRS 974, Institut de Myologie, Paris, France.
authors.forename: Eliska
authors.initials: E
authors.lastname: Vavrova
authors.affiliation: *Institut National de la Santé et de la Recherche Médicale (INSERM), U1016, Institut Cochin, Paris, France; Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche (UMR) 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; and INSERM U974, CNRS UMR 7215, Université Pierre et Marie Curie UMRS 974, Institut de Myologie, Paris, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Lenoir
authors.affiliation: *Institut National de la Santé et de la Recherche Médicale (INSERM), U1016, Institut Cochin, Paris, France; Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche (UMR) 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; and INSERM U974, CNRS UMR 7215, Université Pierre et Marie Curie UMRS 974, Institut de Myologie, Paris, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Ferry
authors.affiliation: *Institut National de la Santé et de la Recherche Médicale (INSERM), U1016, Institut Cochin, Paris, France; Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche (UMR) 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; and INSERM U974, CNRS UMR 7215, Université Pierre et Marie Curie UMRS 974, Institut de Myologie, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Esnous
authors.affiliation: *Institut National de la Santé et de la Recherche Médicale (INSERM), U1016, Institut Cochin, Paris, France; Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche (UMR) 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; and INSERM U974, CNRS UMR 7215, Université Pierre et Marie Curie UMRS 974, Institut de Myologie, Paris, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Ramond
authors.affiliation: *Institut National de la Santé et de la Recherche Médicale (INSERM), U1016, Institut Cochin, Paris, France; Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche (UMR) 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; and INSERM U974, CNRS UMR 7215, Université Pierre et Marie Curie UMRS 974, Institut de Myologie, Paris, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Girard
authors.affiliation: *Institut National de la Santé et de la Recherche Médicale (INSERM), U1016, Institut Cochin, Paris, France; Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche (UMR) 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; and INSERM U974, CNRS UMR 7215, Université Pierre et Marie Curie UMRS 974, Institut de Myologie, Paris, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Bouillaud
authors.affiliation: *Institut National de la Santé et de la Recherche Médicale (INSERM), U1016, Institut Cochin, Paris, France; Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche (UMR) 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; and INSERM U974, CNRS UMR 7215, Université Pierre et Marie Curie UMRS 974, Institut de Myologie, Paris, France carina.prip-buus@inserm.fr.
authors.forename: Carina
authors.initials: C
authors.lastname: Prip-Buus
authors.affiliation: *Institut National de la Santé et de la Recherche Médicale (INSERM), U1016, Institut Cochin, Paris, France; Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche (UMR) 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; and INSERM U974, CNRS UMR 7215, Université Pierre et Marie Curie UMRS 974, Institut de Myologie, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Cohen
mesh_terms: D000367:Age Factors; D000818:Animals; D015153:Blotting, Western; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D015870:Gene Expression; D006003:Glycogen / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008931:Mitochondria, Muscle / Q000378:metabolism* / Q000502:physiology; D018763:Muscle Fatigue / Q000235:genetics / Q000502:physiology; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism* / Q000502:physiology; D009154:Mutation; D010084:Oxidation-Reduction; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055948:Sarcopenia / Q000235:genetics / Q000503:physiopathology; D014162:Transfection
chemical_list: D005227:Fatty Acids; D006003:Glycogen; D002334:Carnitine O-Palmitoyltransferase
keywords: aging; carnitine palmitoyltransferase 1; oxidative capacity; skeletal muscle plasticity