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

Jorge L. Ruas, James P. White, Rajesh R. Rao, Sandra Kleiner, Kevin T. Brannan, Brooke C. Harrison, Nicholas P. Greene, Jun Wu, Jennifer L. Estall, Brian A. Irving, Ian R. Lanza, Kyle A. Rasbach, Mitsuharu Okutsu, K. Sreekumaran Nair, Zhen Yan, Leslie A. Leinwand, Bruce M. Spiegelman

Research output: Contribution to journalArticlepeer-review

383 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1319-1331
Number of pages13
JournalCell
Volume151
Issue number6
DOIs
StatePublished - Dec 7 2012

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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