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Myostatin is a key mediator between energy metabolism and endurance capacity of skeletal muscle.
- Source :
-
American journal of physiology. Regulatory, integrative and comparative physiology [Am J Physiol Regul Integr Comp Physiol] 2014 Aug 15; Vol. 307 (4), pp. R444-54. Date of Electronic Publication: 2014 Jun 25. - Publication Year :
- 2014
-
Abstract
- Myostatin (Mstn) participates in the regulation of skeletal muscle size and has emerged as a regulator of muscle metabolism. Here, we hypothesized that lack of myostatin profoundly depresses oxidative phosphorylation-dependent muscle function. Toward this end, we explored Mstn(-/-) mice as a model for the constitutive absence of myostatin and AAV-mediated overexpression of myostatin propeptide as a model of myostatin blockade in adult wild-type mice. We show that muscles from Mstn(-/-) mice, although larger and stronger, fatigue extremely rapidly. Myostatin deficiency shifts muscle from aerobic toward anaerobic energy metabolism, as evidenced by decreased mitochondrial respiration, reduced expression of PPAR transcriptional regulators, increased enolase activity, and exercise-induced lactic acidosis. As a 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 congenital fiber-type switch toward a glycolytic phenotype of constitutive Mstn(-/-) mice. Hence, we overexpressed myostatin propeptide in adult mice, which did not affect fiber-type distribution, while nonetheless causing increased muscle fatigability, diminished exercise capacity, 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 regulating the delicate balance between muscle mass, muscle force, energy metabolism, and endurance capacity.<br /> (Copyright © 2014 the American Physiological Society.)
- Subjects :
- Animals
Genotype
Glycolysis
Lactic Acid metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Mitochondria, Muscle metabolism
Muscle Fatigue
Myostatin deficiency
Myostatin genetics
Oxygen Consumption
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Peroxisome Proliferator-Activated Receptors genetics
Peroxisome Proliferator-Activated Receptors metabolism
Phenotype
Phosphopyruvate Hydratase metabolism
Running
Signal Transduction
Time Factors
Transcription Factors genetics
Transcription Factors metabolism
Energy Metabolism
Muscle Contraction
Muscle, Skeletal metabolism
Myostatin metabolism
Physical Endurance
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1490
- Volume :
- 307
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Regulatory, integrative and comparative physiology
- Publication Type :
- Academic Journal
- Accession number :
- 24965795
- Full Text :
- https://doi.org/10.1152/ajpregu.00377.2013