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

By J. Ruas, James P. White, Rajesh R. Rao, Sandra Kleiner, Kevin T. Brannan, B. Harrison, N. Greene, Jun Wu, J. Estall, Brian A. Irving and 7 more. Cell, 2012

627 citations recorded by the source corpus.

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 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.

Subfields: Cell Biology, Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/7b5d729c414cdf8e3ff956da322d9cb1993e2d39

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cell Biology

1. M. Hargreaves
2. J. Zierath
3. J. Hawley
4. Michael J. Joyner
5. Jun Wu
6. R. Youle
7. Toren Finkel
8. B. Spiegelman

In Molecular Biology

1. J. Hawley
2. Michael J. Joyner
3. J. Zierath
4. M. Hargreaves
5. Mark P. Jedrychowski
6. B. Spiegelman
7. Steven P. Gygi
8. Jun Wu

In Physiology

1. J. Hawley
2. Michael J. Joyner
3. J. Zierath
4. M. Hargreaves
5. Jun Wu
6. P. Cohen
7. Toren Finkel
8. B. Spiegelman

Citations in the corpus

• Integrative biology of exercise. (2014, positive): “…of either endurance exercise, resistance exercise, or a combination of both endurance and resistance exercise, increases in PGC-1 a 4 were confined to resistance-only and combined exercise training programs, with no changes in this transcript after endur-ance-only training (Ruas et al., 2012).”
• Adaptive thermogenesis in adipocytes: is beige the new brown? (2013, background): “Furthermore, there are multiple splice variants of each, and the specific functions of these are still being elucidated (Ruas et al. 2012).”
• Meteorin-like is a hormone that regulates immune-adipose interactions to increase beige fat thermogenesis (2014, methodology): “Given that PGC-1a4 mRNA is expressed in the skeletal muscle of mice and humans upon resistance training (Ruas et al., 2012), we investigated the regulation of Metrnl in human skeletal muscle following an acute bout of concurrent exercise (resistance followed by endurance exercise; concurrent…”
• The Mitochondrial Basis of Aging (2016, background): “Mitochondrial biogenesis is largely coordinated by the transcriptional coactivator peroxisome proliferator-activated receptor g coactivator-1 a (PGC1a) (Handschin and Spiegelman, 2008; Ruas et al., 2012).”