title: PGC-1alpha plays a functional role in exercise-induced mitochondrial biogenesis and angiogenesis but not fiber-type transformation in mouse skeletal muscle.
abstract: Endurance exercise stimulates peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) expression in skeletal muscle, and forced expression of PGC-1alpha changes muscle metabolism and exercise capacity in mice. However, it is unclear if PGC-1alpha 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-1alpha knockout mice. Interestingly, voluntary running effectively restored the compromised mitochondrial integrity and superoxide dismutase 2 (SOD2) protein expression in skeletal muscle in Pgc-1alpha knockout mice. Thus, PGC-1alpha 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-1alpha function. We conclude that PGC-1alpha is required for complete skeletal muscle adaptations induced by endurance exercise in mice.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Tuoyu
authors.initials: T
authors.lastname: Geng
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Mitsuharu
authors.initials: M
authors.lastname: Okutsu
authors.forename: Xinhe
authors.initials: X
authors.lastname: Yin
authors.forename: Jyeyi
authors.initials: J
authors.lastname: Kwek
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yan
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D045304:Cytochromes c / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008931:Mitochondria, Muscle / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D009119:Muscle Contraction; D018656:Muscle Fibers, Fast-Twitch / Q000378:metabolism* / Q000473:pathology; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D018995:Myosin Heavy Chains / Q000378:metabolism; D018919:Neovascularization, Physiologic; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010641:Phenotype; D010807:Physical Endurance; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D012420:Running; D024744:Skeletal Muscle Myosins / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D000099156:Superoxide Dismutase 2
chemical_list: D045304:Cytochromes c; D003576:Electron Transport Complex IV; D018995:Myosin Heavy Chains; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D024744:Skeletal Muscle Myosins; D013482:Superoxide Dismutase; D015534:Trans-Activators; D014157:Transcription Factors; D000099156:Superoxide Dismutase 2; C485290:Ppargc1a protein, mouse