title: Prmt7 Deficiency Causes Reduced Skeletal Muscle Oxidative Metabolism and Age-Related Obesity.
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.
authors.affiliation: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon, South Korea.
authors.forename: Hyeon-Ju
authors.initials: HJ
authors.lastname: Jeong
authors.affiliation: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon, South Korea.
authors.forename: Hye-Jin
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon, South Korea.
authors.forename: Tuan Anh
authors.initials: TA
authors.lastname: Vuong
authors.affiliation: Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, South Korea.
authors.forename: Kyu-Sil
authors.initials: KS
authors.lastname: Choi
authors.affiliation: Division of Life Science, Korea University, Seoul, South Korea.
authors.forename: Dahee
authors.initials: D
authors.lastname: Choi
authors.affiliation: Division of Life Science, Korea University, Seoul, South Korea.
authors.forename: Sung-Hoi
authors.initials: SH
authors.lastname: Koo
authors.affiliation: Well Aging Research Center, Samsung Advanced Institute of Technology, Samsung Electronics Co. Ltd., Suwon, South Korea.
authors.forename: Sung Chun
authors.initials: SC
authors.lastname: Cho
authors.affiliation: Department of Physiology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon, South Korea.
authors.forename: Hana
authors.initials: H
authors.lastname: Cho
authors.affiliation: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon, South Korea kangj01@skku.edu.
authors.forename: Jong-Sun
authors.initials: JS
authors.lastname: Kang
mesh_terms: D051698:Activating Transcription Factor 2 / Q000235:genetics / Q000378:metabolism; D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D004734:Energy Metabolism / Q000235:genetics*; D005260:Female; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism*; D032446:Myoblasts / Q000378:metabolism; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D010101:Oxygen Consumption / Q000235:genetics; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000235:genetics / Q000378:metabolism; D010805:Physical Conditioning, Animal; D010807:Physical Endurance / Q000235:genetics; D011401:Promoter Regions, Genetic; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D051698:Activating Transcription Factor 2; C497106:Atf2 protein, mouse; D008055:Lipids; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; C570798:PRMT7 protein, mouse; D011484:Protein-Arginine N-Methyltransferases