A PGC-1α Isoform Induced by Resistance Training Regulates Skeletal Muscle Hypertrophy

Department of Cell Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA. Electronic address: .
Cell (Impact Factor: 32.24). 12/2012; 151(6):1319-31. DOI: 10.1016/j.cell.2012.10.050
Source: PubMed


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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    • "A recently discovered splice form of PGC-1α, PGC- 1α4, has no effect on mitochondrial gene regulation. PGC-1α4 is increased with strength training protocols associated with muscle fiber hypertrophy (Ruas et al., 2012). These authors showed that muscle growth by PGC-1α4 is achieved by inducing insulin-like growth factor 1 (IGF-1) and by suppressing myostatin. "

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    • "A total of 50 ml of 5 3 10 9 Pfu of each adenovirus diluted in saline was injected bilaterally (s.c.) into the inguinal fat pads of mice (Ma et al., 2014). For intramuscular delivery of adenovirus, 10 ml of 2 3 10 10 Pfu control or mouse HSF1 adenovirus diluted in saline was injected unilaterally into the contralateral lower limbs of mice (Ruas et al., 2012). Mice were either sacrificed at the fourth day after viral delivery or were celastrol treated as noted, and tissues were dissected for further analysis or monitored for changes in body temperature under cold environment for 3 hr. "
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    • "Thus, the PGC-1α gene has the potential to produce at least six transcripts (Chang et al. 2012). However, another study in mouse skeletal muscle found only two previously described isoforms (PGC-1α-a and NT-PGC-1α-b mRNAs), as well as two additional isoforms (PGC-1α-2 and PGC-1α-3 mRNAs) with multiple splicing between exons (Ruas et al. 2012). Other tissue-specific promoters and isoforms have been described in human nervous tissue (Soyal et al. 2012) and liver (Felder et al. 2011). "
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