| First Author | Tadaishi M | Year | 2011 |
| Journal | PLoS One | Volume | 6 |
| Issue | 12 | Pages | e28290 |
| PubMed ID | 22174785 | Mgi Jnum | J:182259 |
| Mgi Id | MGI:5315070 | Doi | 10.1371/journal.pone.0028290 |
| Citation | Tadaishi M, et al. (2011) Skeletal muscle-specific expression of PGC-1alpha-b, an exercise-responsive isoform, increases exercise capacity and peak oxygen uptake. PLoS One 6(12):e28290 |
| abstractText | BACKGROUND: Maximal oxygen uptake (VO(2max)) predicts mortality and is associated with endurance performance. Trained subjects have a high VO(2max) due to a high cardiac output and high metabolic capacity of skeletal muscles. Peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha), a nuclear receptor coactivator, promotes mitochondrial biogenesis, a fiber-type switch to oxidative fibers, and angiogenesis in skeletal muscle. Because exercise training increases PGC-1alpha in skeletal muscle, PGC-1alpha-mediated changes may contribute to the improvement of exercise capacity and VO(2max). There are three isoforms of PGC-1alpha mRNA. PGC-1alpha-b protein, whose amino terminus is different from PGC-1alpha-a protein, is a predominant PGC-1alpha isoform in response to exercise. We investigated whether alterations of skeletal muscle metabolism by overexpression of PGC-1alpha-b in skeletal muscle, but not heart, would increase VO(2max) and exercise capacity. METHODOLOGY/PRINCIPAL FINDINGS: Transgenic mice showed overexpression of PGC-1alpha-b protein in skeletal muscle but not in heart. Overexpression of PGC-1alpha-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. CONCLUSIONS/SIGNIFICANCE: 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-1alpha-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. |
