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A novel PGC‐1á isoform induced by resistance training regulates skeletal muscle hypertrophy
Author(s) -
White James,
Ruas Jorge,
Rao Rajesh,
Kleiner Sandra,
Wu Jun,
Spiegelman Bruce
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.940.18
Subject(s) - skeletal muscle , myostatin , muscle hypertrophy , gene isoform , coactivator , endocrinology , biology , mitochondrial biogenesis , medicine , myocyte , myokine , alternative splicing , wasting , sarcopenia , mitochondrion , microbiology and biotechnology , gene , transcription factor , biochemistry
PGC‐1α is a transcriptional coactivator induced by exercise that gives muscle many of the best known adaptations to endurancetype exercise, but has no effects on muscle strength or hypertrophy. We have identified a novel 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 novel PGC‐1α protein that regulates and coordinates factors involved in skeletal muscle hypertrophy.