title: ActRIIB blockade increases force-generating capacity and preserves energy supply in exercising mdx mouse muscle in vivo.
abstract: Postnatal blockade of the activin type IIB receptor (ActRIIB) represents a promising therapeutic strategy for counteracting dystrophic muscle wasting. However, its impact on muscle function and bioenergetics remains poorly documented in physiologic conditions. We have investigated totally noninvasively the effect of 8-wk administration of either soluble ActRIIB signaling inhibitor (sActRIIB-Fc) or vehicle PBS (control) on gastrocnemius muscle force-generating capacity, energy metabolism, and anatomy in dystrophic mdx mice using magnetic resonance (MR) imaging and dynamic [31P]-MR spectroscopy ([31P]-MRS) in vivo ActRIIB inhibition increased muscle volume (+33%) without changing fiber-type distribution, and increased basal animal oxygen consumption (+22%) and energy expenditure (+23%). During an in vivo standardized fatiguing exercise, maximum and total absolute contractile forces were larger (+40 and 24%, respectively) in sActRIIB-Fc treated animals, whereas specific force-generating capacity and fatigue resistance remained unaffected. Furthermore, sActRIIB-Fc administration did not alter metabolic fluxes, ATP homeostasis, or contractile efficiency during the fatiguing bout of exercise, although it dramatically reduced the intrinsic mitochondrial capacity for producing ATP. Overall, sActRIIB-Fc treatment increased muscle mass and strength without altering the fundamental weakness characteristic of dystrophic mdx muscle. These data support the clinical interest of ActRIIB blockade for reversing dystrophic muscle wasting.-Béchir, N., Pecchi, E., Vilmen, C., Le Fur, Y., Amthor, H., Bernard, M., Bendahan, D., Giannesini, B. ActRIIB blockade increases force-generating capacity and preserves energy supply in exercising mdx mouse muscle in vivo.
authors.affiliation: Aix-Marseille Université, Centre National de la Recherche Scientifique, Centre de Résonance Magnétique Biologique et Médicale, Unité Mixte de Recherche 7339, Marseille, France.
authors.forename: Nelly
authors.initials: N
authors.lastname: Béchir
authors.affiliation: Aix-Marseille Université, Centre National de la Recherche Scientifique, Centre de Résonance Magnétique Biologique et Médicale, Unité Mixte de Recherche 7339, Marseille, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Pecchi
authors.affiliation: Aix-Marseille Université, Centre National de la Recherche Scientifique, Centre de Résonance Magnétique Biologique et Médicale, Unité Mixte de Recherche 7339, Marseille, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Vilmen
authors.affiliation: Aix-Marseille Université, Centre National de la Recherche Scientifique, Centre de Résonance Magnétique Biologique et Médicale, Unité Mixte de Recherche 7339, Marseille, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Le Fur
authors.affiliation: Université de Versailles Saint-Quentin-en-Yvelines, Unités de Formation et de Recherche des Sciences de la Santé, INSERM U1179, Laboratoire International Associé, Biologie Appliquée Handicap Neuromusculaire, Cellules Souches Mésenchymateuses, Saint Quentin en Yvelines Therapeutics, Montigny-le-Bretonneux, France; and Service Génétique Médicale, Centre Hospitalier Universitaire Necker-Enfants Malades, Université Paris Descartes, Paris, France.
authors.forename: Helge
authors.initials: H
authors.lastname: Amthor
authors.affiliation: Aix-Marseille Université, Centre National de la Recherche Scientifique, Centre de Résonance Magnétique Biologique et Médicale, Unité Mixte de Recherche 7339, Marseille, France.
authors.forename: Monique
authors.initials: M
authors.lastname: Bernard
authors.affiliation: Aix-Marseille Université, Centre National de la Recherche Scientifique, Centre de Résonance Magnétique Biologique et Médicale, Unité Mixte de Recherche 7339, Marseille, France.
authors.forename: David
authors.initials: D
authors.lastname: Bendahan
authors.affiliation: Aix-Marseille Université, Centre National de la Recherche Scientifique, Centre de Résonance Magnétique Biologique et Médicale, Unité Mixte de Recherche 7339, Marseille, France; benoit.giannesini@univ-amu.fr.
authors.forename: Benoît
authors.initials: B
authors.lastname: Giannesini
mesh_terms: D030301:Activin Receptors, Type II / Q000037:antagonists & inhibitors*; D000818:Animals; D001835:Body Weight / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D051379:Mice; D018101:Mice, Inbred mdx; D023421:Models, Animal; D009119:Muscle Contraction / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009137:Muscular Dystrophy, Animal / Q000473:pathology*; D010805:Physical Conditioning, Animal / Q000379:methods
chemical_list: D030301:Activin Receptors, Type II; C425584:activin receptor type II-B
keywords: Duchenne muscular dystrophy; muscle fatigue; myostatin inhibition; skeletal muscle hypertrophy