PGC-1α plays a functional role in exercise-induced mitochondrial biogenesis and angiogenesis but not fiber-type transformation in mouse skeletal muscle

Geng T, Li P, Okutsu M, Yin X, Kwek J, Zhang M, Yan Z. PGC-1 alpha plays a functional role in exercise-induced mitochondrial biogenesis and angiogenesis but not fiber-type transformation in mouse skeletal muscle. Am J Physiol Cell Physiol 298: C572-C579, 2010. First published December 23, 2009; doi: 10.1152/ajpcell.00481.2009. Endurance exercise stimulates peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) expression in skeletal muscle, and forced expression of PGC-1 alpha changes muscle metabolism and exercise capacity in mice. However, it is unclear if PGC-1 alpha is indispensible for endurance exercise-induced metabolic and contractile adaptations in skeletal muscle. In this study, we showed that endurance exercise-induced expression of mitochondrial enzymes (cytochrome oxidase IV and cytochrome c) and increases of platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31)-positive endothelial cells in skeletal muscle, but not IIb-to-IIa fiber-type transformation, were significantly attenuated in muscle-specific Pgc-1 alpha knockout mice. Interestingly, voluntary running effectively restored the compromised mitochondrial integrity and superoxide dismutase 2 (SOD2) protein expression in skeletal muscle in Pgc-1 alpha knockout mice. Thus, PGC-1 alpha plays a functional role in endurance exercise-induced mitochondrial biogenesis and angiogenesis, but not IIb-to-IIa fiber-type transformation in mouse skeletal muscle, and the improvement of mitochondrial morphology and antioxidant defense in response to endurance exercise may occur independently of PGC-1 alpha function. We conclude that PGC-1 alpha is required for complete skeletal muscle adaptations induced by endurance exercise in mice.