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Enhanced exercise and regenerative capacity in a mouse model that violates size constraints of oxidative muscle fibres.

Omairi, S and Matsakas, A and Degens, H and Kretz, O and Hansson, KA and Solbrå, AV and Bruusgaard, JC and Joch, B and Sartori, R and Giallourou, N and Mitchell, R and Collins-Hooper, H and Foster, K and Pasternack, A and Ritvos, O and Sandri, M and Narkar, V and Swann, JR and Huber, TB and Patel, K (2016) Enhanced exercise and regenerative capacity in a mouse model that violates size constraints of oxidative muscle fibres. Elife, 5. ISSN 2050-084X

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Abstract

A central tenet of skeletal muscle biology is the existence of an inverse relationship between the oxidative fibre capacity and its size. However, robustness of this relationship is unknown. We show that superimposition of Estrogen-related receptor gamma (Errγ) on the myostatin (Mtn) mouse null background (Mtn(-/-)/Errγ(Tg/+)) results in hypertrophic muscle with a high oxidative capacity thus violating the inverse relationship between fibre size and oxidative capacity. We also examined the canonical view that oxidative muscle phenotype positively correlate with Satellite cell number, the resident stem cells of skeletal muscle. Surprisingly, hypertrophic fibres from Mtn(-/-)/Errγ(Tg/+) mouse showed satellite cell deficit which unexpectedly did not affect muscle regeneration. These observations 1) challenge the concept of a constraint between fibre size and oxidative capacity and 2) indicate the important role of the microcirculation in the regenerative capacity of a muscle even when satellite cell numbers are reduced.

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