[HTML][HTML] A PGC-1α isoform induced by resistance training regulates skeletal muscle hypertrophy

JL Ruas, JP White, RR Rao, S Kleiner, KT Brannan… - Cell, 2012 - cell.com
JL Ruas, JP White, RR Rao, S Kleiner, KT Brannan, BC Harrison, NP Greene, J Wu
Cell, 2012cell.com
PGC-1α 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-1α (PGC-1α4) that results from alternative
promoter usage and splicing of the primary transcript. PGC-1α4 is highly expressed in
exercised muscle but does not regulate most known PGC-1α targets such as the
mitochondrial OXPHOS genes. Rather, it specifically induces IGF1 and represses myostatin …
Summary
PGC-1α 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-1α (PGC-1α4) that results from alternative promoter usage and splicing of the primary transcript. PGC-1α4 is highly expressed in exercised muscle but does not regulate most known PGC-1α targets such as the mitochondrial OXPHOS genes. Rather, it specifically induces IGF1 and represses myostatin, and expression of PGC-1α4 in vitro and in vivo induces robust skeletal muscle hypertrophy. Importantly, mice with skeletal muscle-specific transgenic expression of PGC-1α4 show increased muscle mass and strength and dramatic resistance to the muscle wasting of cancer cachexia. Expression of PGC-1α4 is preferentially induced in mouse and human muscle during resistance exercise. These studies identify a PGC-1α protein that regulates and coordinates factors involved in skeletal muscle hypertrophy.
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