נק' מוניטין:
58,705
Am J Physiol Regul Integr Comp Physiol. 2014 Jun 25. pii: ajpregu.00377.2013. [Epub ahead of print]
Myostatin is a key mediator between energy metabolism and endurance capacity of skeletal muscle.
Mouisel E1, Relizani K, Mille-Hamard L2, Denis R, Hourde C3, Agbulut O4, Patel K5, Arandel L, Morales-Gonzalez S, Vignaud A6, Garcia L, Ferry A6, Luquet S, Billat VL7, Ventura-Clapier R8, Schuelke M, Amthor H9.
Author information
Abstract
Myostatin (Mstn) participates in the regulation of skeletal muscle size and emerges as a reg-ulator of muscle metabolism. We here hypothesized that lack of myostatin profoundly de-presses oxidative phosphorylation dependent muscle function. For this extent, we explored Mstn-/- mice as a model for the constitutive absence of myostatin and AAV-mediated over-expression of myostatin propeptide as a model of myostatin blockade in adult wildtype mice. We show that muscles from Mstn-/- mice, although larger and stronger, fatigue ex-tremely rapidly. Myostatin deficiency shifts muscle from aerobic towards anaerobic energy metabolism as evidenced by decreased mitochondrial respiration, reduced expression of PPAR transcriptional regulators, increased enolase activity, and exercise induced lactic acido-sis. In consequence, constitutively reduced myostatin signaling diminishes exercise capacity, while the hypermuscular state of Mstn-/- mice increases oxygen consumption and the energy cost of running. We wondered whether these results are the mere consequence of the con-genital fiber-type switch towards a glycolytic phenotype of constitutive Mstn-/- mice. Hence we over-expressed myostatin propeptide in adult mice, which did not affect fiber-type dis-tribution, while nonetheless causing increased muscle fatigability, diminished exercise ca-pacity and decreased Pparb/d and Pgc1a expression. In conclusion, our results suggest that myostatin endows skeletal muscle with high oxidative capacity and low fatigability, thus reg-ulating the delicate balance between muscle mass, muscle force, energy metabolism and endurance capacity.
Myostatin is a key mediator between energy metabolism and endurance capacity of skeletal muscle.
Mouisel E1, Relizani K, Mille-Hamard L2, Denis R, Hourde C3, Agbulut O4, Patel K5, Arandel L, Morales-Gonzalez S, Vignaud A6, Garcia L, Ferry A6, Luquet S, Billat VL7, Ventura-Clapier R8, Schuelke M, Amthor H9.
Author information
Abstract
Myostatin (Mstn) participates in the regulation of skeletal muscle size and emerges as a reg-ulator of muscle metabolism. We here hypothesized that lack of myostatin profoundly de-presses oxidative phosphorylation dependent muscle function. For this extent, we explored Mstn-/- mice as a model for the constitutive absence of myostatin and AAV-mediated over-expression of myostatin propeptide as a model of myostatin blockade in adult wildtype mice. We show that muscles from Mstn-/- mice, although larger and stronger, fatigue ex-tremely rapidly. Myostatin deficiency shifts muscle from aerobic towards anaerobic energy metabolism as evidenced by decreased mitochondrial respiration, reduced expression of PPAR transcriptional regulators, increased enolase activity, and exercise induced lactic acido-sis. In consequence, constitutively reduced myostatin signaling diminishes exercise capacity, while the hypermuscular state of Mstn-/- mice increases oxygen consumption and the energy cost of running. We wondered whether these results are the mere consequence of the con-genital fiber-type switch towards a glycolytic phenotype of constitutive Mstn-/- mice. Hence we over-expressed myostatin propeptide in adult mice, which did not affect fiber-type dis-tribution, while nonetheless causing increased muscle fatigability, diminished exercise ca-pacity and decreased Pparb/d and Pgc1a expression. In conclusion, our results suggest that myostatin endows skeletal muscle with high oxidative capacity and low fatigability, thus reg-ulating the delicate balance between muscle mass, muscle force, energy metabolism and endurance capacity.
