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Article Dans Une Revue FASEB Journal Année : 2016

ActRIIB blockade increases force‐generating capacity and preserves energy supply in exercising mdx mouse muscle in vivo

Résumé

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 forcegenerating 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.,
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hal-03548287 , version 1 (01-02-2022)

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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, 2016, 30 (10), pp.3551-3562. ⟨10.1096/fj.201600271RR⟩. ⟨hal-03548287⟩
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