title: Lack of myostatin impairs mechanical performance and ATP cost of contraction in exercising mouse gastrocnemius muscle in vivo.
abstract: Although it is well established that the lack of myostatin (Mstn) promotes skeletal muscle hypertrophy, the corresponding changes regarding force generation have been studied mainly in vitro and remain conflicting. Furthermore, the metabolic underpinnings of these changes are very poorly documented. To clarify this issue, we have investigated strictly noninvasively in vivo the impact of the lack of Mstn on gastrocnemius muscle function and energetics in Mstn-targeted knockout (Mstn-/-) mice using ¹H-magnetic resonance (MR) imaging and ³¹P-MR spectroscopy during maximal repeated isometric contractions induced by transcutaneous electrostimulation. In Mstn-/- animals, although body weight, gastrocnemius muscle volume, and absolute force were larger (+38, +118, and +34%, respectively) compared with wild-type (Mstn+/+) mice, specific force (calculated from MR imaging measurements) was significantly lower (-36%), and resistance to fatigue was decreased. Besides, Mstn deficiency did not affect phosphorylated compound concentrations and intracellular pH at rest but caused a large increase in ATP cost of contraction (up to +206% compared with Mstn+/+) throughout the stimulation period. Further, Mstn deficiency limits the shift toward oxidative metabolism during muscle activity despite the fact that oxidative ATP synthesis capacity was not altered. Our data demonstrate in vivo that the absence of Mstn impairs both mechanical performance and energy cost of contraction in hypertrophic muscle. These findings must be kept in mind when considering Mstn as a potential therapeutic target for increasing muscle mass in patients suffering from muscle-wasting disorders.
authors: Aix-Marseille Université, Centre National de la Recherche Scientifique (CNRS), Centre de Résonance Magnétique Biologique et Médicale (CRMBM) UMR 7339, 13385, Marseille, France. benoit.giannesini@univ-amu.fr
authors: Benoît
authors: B
authors: Giannesini
authors: Christophe
authors: C
authors: Vilmen
authors: Helge
authors: H
authors: Amthor
authors: Monique
authors: M
authors: Bernard
authors: David
authors: D
authors: Bendahan
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001696:Biomechanical Phenomena / Q000235:genetics; D004558:Electric Stimulation; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology*; D009133:Muscular Atrophy / Q000378:metabolism / Q000503:physiopathology; D055435:Myostatin / Q000235:genetics* / Q000378:metabolism*; D010805:Physical Conditioning, Animal / Q000502:physiology*
chemical_list: C525912:Mstn protein, mouse; D055435:Myostatin; D000255:Adenosine Triphosphate
keywords: adenosine 5′-triphosphate; energy metabolism; fatigue; hypertrophy; nuclear magnetic resonance; skeletal muscle