Skeletal Muscle-Specific Expression of PGC-1α-b, an Exercise-Responsive Isoform, Increases Exercise Capacity and Peak Oxygen Uptake
Open Access
- 8 December 2011
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 6 (12), e28290
- https://doi.org/10.1371/journal.pone.0028290
Abstract
Maximal oxygen uptake (VO2max) predicts mortality and is associated with endurance performance. Trained subjects have a high VO2max due to a high cardiac output and high metabolic capacity of skeletal muscles. Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a nuclear receptor coactivator, promotes mitochondrial biogenesis, a fiber-type switch to oxidative fibers, and angiogenesis in skeletal muscle. Because exercise training increases PGC-1α in skeletal muscle, PGC-1α-mediated changes may contribute to the improvement of exercise capacity and VO2max. There are three isoforms of PGC-1α mRNA. PGC-1α-b protein, whose amino terminus is different from PGC-1α-a protein, is a predominant PGC-1α isoform in response to exercise. We investigated whether alterations of skeletal muscle metabolism by overexpression of PGC-1α-b in skeletal muscle, but not heart, would increase VO2max and exercise capacity. Transgenic mice showed overexpression of PGC-1α-b protein in skeletal muscle but not in heart. Overexpression of PGC-1α-b promoted mitochondrial biogenesis 4-fold, increased the expression of fatty acid transporters, enhanced angiogenesis in skeletal muscle 1.4 to 2.7-fold, and promoted exercise capacity (expressed by maximum speed) by 35% and peak oxygen uptake by 20%. Across a broad range of either the absolute exercise intensity, or the same relative exercise intensities, lipid oxidation was always higher in the transgenic mice than wild-type littermates, suggesting that lipid is the predominant fuel source for exercise in the transgenic mice. However, muscle glycogen usage during exercise was absent in the transgenic mice. Increased mitochondrial biogenesis, capillaries, and fatty acid transporters in skeletal muscles may contribute to improved exercise capacity via an increase in fatty acid utilization. Increases in PGC-1α-b protein or function might be a useful strategy for sedentary subjects to perform exercise efficiently, which would lead to prevention of life-style related diseases and increased lifespan.Keywords
This publication has 61 references indexed in Scilit:
- Genomic predictors of the maximal O2 uptake response to standardized exercise training programsJournal of Applied Physiology, 2011
- Review: Mortality trends in the general population: the importance of cardiorespiratory fitnessJournal of Psychopharmacology, 2010
- Peroxisome Proliferator-activated Receptor γ Co-activator 1α (PGC-1α) and Sirtuin 1 (SIRT1) Reside in MitochondriaJournal of Biological Chemistry, 2010
- The transcriptional coactivator PGC-1α mediates exercise-induced angiogenesis in skeletal muscleProceedings of the National Academy of Sciences of the United States of America, 2009
- Cardiorespiratory Fitness as a Quantitative Predictor of All-Cause Mortality and Cardiovascular Events in Healthy Men and WomenJama-Journal Of The American Medical Association, 2009
- Aerobic Interval Training Versus Continuous Moderate Exercise as a Treatment for the Metabolic SyndromeCirculation, 2008
- Fast/Glycolytic Muscle Fiber Growth Reduces Fat Mass and Improves Metabolic Parameters in Obese MiceCell Metabolism, 2008
- Nur77 Coordinately Regulates Expression of Genes Linked to Glucose Metabolism in Skeletal MuscleMolecular Endocrinology, 2007
- Molecular regulation of vessel maturationNature Medicine, 2003
- Strategies to Enhance Fat Utilisation During ExerciseSports Medicine, 1998