ActRIIB blockade increases force‐generating capacity and preserves energy supply in exercising mdx mouse muscle in vivo. Issue 10 (14th July 2016)

• Record Type: Journal Article
• Authors: Béchir, Nelly; Pecchi, Emilie; Vilmen, Christophe; Le Fur, Yann; Amthor, Helge; Bernard, Monique; Bendahan, David; Giannesini, Benoît
• Is Part Of: FASEB journal. Volume 30:Issue 10(2016)
• Page Start: 3551
• Page End: 3562
• Publication Date: 2016-07-14
• Subjects: skeletal muscle hypertrophy -- myostatin inhibition -- Duchenne muscular dystrophy -- muscle fatigue; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.201600271RR
• Languages: English
• ISSNs: 0892-6638

Abstract

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 . FASEB J. 30, 3551–3562 (2016). www.fasebj.org