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Choi, Jang Hyun
Lab of Diabetes and Metabolism (LDM)
Research Interests
  • Diabetes, Metabolic Disorders, PPARg, Gene Regulation, Anti-Diabetic Drug

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The Unfolded Protein Response Mediates Adaptation to Exercise in Skeletal Muscle through a PGC-1 alpha/ATF6 alpha Complex

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Title
The Unfolded Protein Response Mediates Adaptation to Exercise in Skeletal Muscle through a PGC-1 alpha/ATF6 alpha Complex
Author
Wu, JunRuas, Jorge L.Estall, Jennifer L.Rasbach, Kyle A.Choi, Jang HyunYe, LiBostroem, PontusTyra, Heather M.Crawford, Robert W.Campbell, Kevin P.Rutkowski, D. ThomasKaufman, Randal J.Spiegelman, Bruce M.
Issue Date
2011-02
Publisher
CELL PRESS
Citation
CELL METABOLISM, v.13, no.2, pp.160 - 169
Abstract
Exercise has been shown to be effective for treating obesity and type 2 diabetes. However, the molecular mechanisms for adaptation to exercise training are not fully understood. Endoplasmic reticulum (ER) stress has been linked to metabolic dysfunction. Here we show that the unfolded protein response (UPR), an adaptive response pathway that maintains ER homeostasis upon luminal stress, is activated in skeletal muscle during exercise and adapts skeletal muscle to exercise training. The transcriptional coactivator PGC-1 alpha, which regulates several exercise-associated aspects of skeletal muscle function, mediates the UPR in myotubes and skeletal muscle through coactivation of ATF6 alpha. Efficient recovery from acute exercise is compromised in ATF6 alpha(-/-) mice. Blocking ER-stress-related cell death via deletion of CHOP partially rescues the exercise intolerance phenotype in muscle-specific PGC-1 alpha KO mice. These findings suggest that modulation of the UPR through PGC1 alpha represents an alternative avenue to improve skeletal muscle function and achieve metabolic benefits.
URI
https://scholarworks.unist.ac.kr/handle/201301/7225
URL
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=79551510124
DOI
10.1016/j.cmet.2011.01.003
ISSN
1550-4131
Appears in Collections:
BIO_Journal Papers
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