Cell
Volume 151, Issue 6, 7 December 2012, Pages 1319-1331
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Article
A PGC-1α Isoform Induced by Resistance Training Regulates Skeletal Muscle Hypertrophy

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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.

Highlights

► Three PGC-1α variants are generated by alternative promoter use and splicing ► PGC-1α4 induces skeletal muscle hypertrophy ► PGC-1α4 muscle-specific transgenics have increased muscle mass and strength ► PGC-1α4 transgenic mice are resistant to cancer-induced cachexia

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These authors contributed equally to this work

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These authors contributed equally to this work

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Present address: Department of Physiology and Pharmacology, Karolinska Institutet, S-171 77 Stockholm, Sweden