Skeletal Muscle Fiber-type Switching, Exercise Intolerance, and Myopathy in PGC-1α Muscle-specific Knock-out Animals
Year: 2007
Type: article
Abstract: The transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) is a key integrator of neuromuscular activity in skeletal muscle. Ectopic expression of PGC-1alpha in muscle results in increased mitochondrial number and function as well as an increase in oxidative, fatigue-resistant muscle fibers. Whole body PGC-1alpha knock-out mice have a very complex phenotype but do not have a marked skeletal muscle phenotype. We thus analyzed skeletal muscle-specific PGC-1alpha knock-out mice to identify a specific role for PGC-1alpha in skeletal muscle function. These mice exhibit a shift from oxidative type I and IIa toward type IIx and IIb muscle fibers. Moreover, skeletal muscle-specific PGC-1alpha knock-out animals have reduced endurance capacity and exhibit fiber damage and elevated markers of inflammation following treadmill running. Our data demonstrate a critical role for PGC-1alpha in maintenance of normal fiber type composition and of muscle fiber integrity following exertion.
Source: Journal of Biological Chemistry
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
Funders: National Science Foundation, Muscular Dystrophy Association, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Universität Zürich, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases
Awards: G150446594, Molecular mechanisms regulating skeletal muscle plasticity, AMPK-Ulk1 in Exercise-Induced Mitophagy in Skeletal Muscle, PGC1 proteins, meteorin-like and energy homeostasis, PGC1alpha and Irisin in the Control of Diabetes and Obesity, G9000034354, Boston Area Nutrition Obesity Research Center (NORC)
OpenAlex ID: W2020444654