Résumé :
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The function of myostatin to restrict growth of the body musculature is often regarded as disadvantageous, because muscle prowess commonly associates with health and fitness.Here, we show that larger skeletal muscle that developed in absence of myostatin fatigues extremely rapidly both in myostatin deficient mouse (Mstn-/-) and following myostatin blockade in adult mice. Larger phosphocreatine depletion in contracting Mstn-/- muscle suggests that the increased fatigability results from accumulation of inorganic phosphate, a by-product of energy metabolism. Moreover, upon exercise Mstn-/- muscle acidifies to a larger extent when compared to wildtype muscle causing a non-proportional increase in serum lactate. Such increase in anaerobic glucose metabolism in Mstn-/- muscle was associated with an up to 42% decrease of mitochondrial respiration complex activity. In consequence, Mstn-/- mice failed during aerobic exercise as evidenced by a 28% lower critical speed. Remarkably, despite a switch from aerobic towards anaerobic energy metabolism, the maximal rate of oxygen consumption (VO2max) increases by 14% in Mstn-/- mice owing to the excessively sized body musculature. However, larger VO2max was reached at lower running velocity and energy cost of running increased in hypermuscular Mstn-/- mice. Finally, myostatin strongly stimulates transcription of PPARs mRNAs in myoblast cultures, whereas PPARs are down-regulated in Mstn-/- muscle, suggesting that myostatin regulates oxidative metabolism via PPAR transcriptional regulators (see also poster by Karima Relizani). In conclusion, myostatin links smaller skeletal muscle with high oxidative metabolism, thereby reducing muscle fatigability and optimising the balance between muscle mass, exercise dependent energy expenditure and endurance exercise capacity.
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