Prmt7 deficiency causes reduced skeletal muscle oxidative metabolism and age-related obesity

Hyeon Ju Jeong, Hye Jin Lee, Tuan Anh Vuong, Kyu Sil Choi, Dahee Choi, Seung-Hoi Koo, Sung Chun Cho, Hana Cho, Jong Sun Kang

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Maintenance of skeletal muscle function is critical for metabolic health and the disruption of which exacerbates many chronic diseases such as obesity and diabetes. Skeletal muscle responds to exercise or metabolic demands by a fiber-type switch regulated by signaling-transcription networks that remains to be fully defined. Here, we report that protein arginine methyltransferase 7 (Prmt7) is a key regulator for skeletal muscle oxidative metabolism. Prmt7 is expressed at the highest levels in skeletal muscle and decreased in skeletal muscles with age or obesity. Prmt7-/- muscles exhibit decreased oxidative metabolism with decreased expression of genes involved in muscle oxidative metabolism, including PGC-1α. Consistently, Prmt7-/- mice exhibited significantly reduced endurance exercise capacities. Furthermore, Prmt7-/- mice exhibit decreased energy expenditure, which might contribute to the exacerbated age-related obesity of Prmt7-/- mice. Similarly to Prmt7-/- muscles, Prmt7 depletion in myoblasts also reduces PGC-1α expression and PGC-1α-promoter driven reporter activities. Prmt7 regulates PGC-1α expression through interaction with and activation of p38 mitogen-activated protein kinase (p38MAPK), which in turn activates ATF2, an upstream transcriptional activator for PGC-1α. Taken together, Prmt7 is a novel regulator for muscle oxidative metabolism via activation of p38MAPK/ATF2/PGC-1α.

Original languageEnglish
Pages (from-to)1868-1882
Number of pages15
JournalDiabetes
Volume65
Issue number7
DOIs
Publication statusPublished - 2016 Jul 1

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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  • Cite this

    Jeong, H. J., Lee, H. J., Vuong, T. A., Choi, K. S., Choi, D., Koo, S-H., Cho, S. C., Cho, H., & Kang, J. S. (2016). Prmt7 deficiency causes reduced skeletal muscle oxidative metabolism and age-related obesity. Diabetes, 65(7), 1868-1882. https://doi.org/10.2337/db15-1500