期刊
CELL
卷 151, 期 6, 页码 1319-1331出版社
CELL PRESS
DOI: 10.1016/j.cell.2012.10.050
关键词
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资金
- NIH [DK061562, 5K01AR55676-2, T32HL07284, AR050429, GM29090]
- Novartis
- Wenner-Gren Foundations, Sweden
- AHA [09POST2010078, 12SDG8070003]
- Novartis, Inc.
- [RR024151]
- [AG09531]
- Novo Nordisk Fonden [NNF12OC1016062] Funding Source: researchfish
PGC-1 alpha is a transcriptional coactivator induced by exercise that gives muscle many of the best known adaptations to endurance-type exercise but has no effects on muscle strength or hypertrophy. We have identified a form of PGC-1 alpha (PGC-1 alpha 4) that results from alternative promoter usage and splicing of the primary transcript. PGC-1 alpha 4 is highly expressed in exercised muscle but does not regulate most known PGC-1 alpha targets such as the mitochondrial OXPHOS genes. Rather, it specifically induces IGF1 and represses myostatin, and expression of PGC-1 alpha 4 in vitro and in vivo induces robust skeletal muscle hypertrophy. Importantly, mice with skeletal muscle-specific transgenic expression of PGC-1 alpha 4 show increased muscle mass and strength and dramatic resistance to the muscle wasting of cancer cachexia. Expression of PGC-1 alpha 4 is preferentially induced in mouse and human muscle during resistance exercise. These studies identify a PGC-1 alpha protein that regulates and coordinates factors involved in skeletal muscle hypertrophy.
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