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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 [(31)P]-MR spectroscopy ([(31)P]-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.
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Submitted on : Tuesday, January 3, 2017 - 3:55:06 PM
Last modification on : Saturday, March 12, 2022 - 12:42:04 PM

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Nelly Béchir, Emilie Pecchi, Christophe Vilmen, Yann Le Fur, Helge Amthor, et al.. ActRIIB blockade increases force-generating capacity and preserves energy supply in exercising mdx mouse muscle in vivo. FASEB Journal, Federation of American Society of Experimental Biology, 2016, 30 (10), pp.3551--3562. ⟨10.1096/fj.201600271RR⟩. ⟨hal-01425491⟩

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