title: PRMT3 regulates hepatic lipogenesis through direct interaction with LXRα.
abstract: Arginine methylation is responsible for diverse biological functions and is mediated by protein arginine methyltransferases (PRMTs). Nonalcoholic fatty liver disease (NAFLD) is accompanied by excessive hepatic lipogenesis via liver X receptor α (LXRα). Thus we examined the pathophysiological role of PRMTs in NAFLD and their relationship with LXRα. In this study, palmitic acid (PA) treatment increased PRMT3, which is correlated with the elevation of hepatic lipogenic proteins. The expression of lipogenic proteins was increased by PRMT3 overexpression, but decreased by PRMT3 silencing and use of the PRMT3 knockout (KO) mouse embryonic fibroblast cell line. PRMT3 also increased the transcriptional activity of LXRα by directly binding with LXRα in a methylation-independent manner. In addition, PA treatment translocated PRMT3 to the nucleus. In animal models, a high-fat diet increased the LXRα and PRMT3 expressions and binding, which was not observed in LXRα KO mice. Furthermore, increased PRMT3 expression and its binding with LXRα were observed in NAFLD patients. Taken together, LXRα and PRMT3 expression was increased in cellular and mouse models of NAFLD and human patients, and PRMT3 translocated into the nucleus bound with LXRα as a transcriptional cofactor, which induced lipogenesis. In conclusion, PRMT3 translocation by PA is coupled to the binding of LXRα, which is responsible for the onset of fatty liver.
authors.affiliation: College of Veterinary Medicine, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Dong-il
authors.initials: DI
authors.lastname: Kim
authors.affiliation: College of Veterinary Medicine, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Min-jung
authors.initials: MJ
authors.lastname: Park
authors.affiliation: Metabolism and Functionality Research Group, R&D Division, World Institute of Kimchi, Gwangju, Republic of Korea.
authors.forename: Seul-ki
authors.initials: SK
authors.lastname: Lim
authors.affiliation: Korea Basic Science Institute, Gwangju Center at Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Jae-il
authors.initials: JI
authors.lastname: Park
authors.affiliation: Department of Ophthalmology, Chonnam National University Medical School and Hospital, Gwangju, Republic of Korea.
authors.forename: Kyung-chul
authors.initials: KC
authors.lastname: Yoon
authors.affiliation: Department of Verterinary Physiology, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.
authors.forename: Ho-jae
authors.initials: HJ
authors.lastname: Han
authors.affiliation: Molecular Nutrition Unit, Department of Bioscience and Nutrition, Karolinska Institutet, Stockholm, Sweden Center for Nuclear Receptors and Cell Signaling, University of Houston, Houston, TX.
authors.forename: Jan-åke
authors.initials: JÅ
authors.lastname: Gustafsson
authors.affiliation: Department of Microbiology, Ewha Womans University School of Medicine, Seoul, Republic of Korea.
authors.forename: Jae-hyang
authors.initials: JH
authors.lastname: Lim
authors.affiliation: College of Veterinary Medicine, Chonnam National University, Gwangju, Republic of Korea parksh@chonnam.ac.kr.
authors.forename: Soo-hyun
authors.initials: SH
authors.lastname: Park
mesh_terms: D000368:Aged; D000818:Animals; D059305:Diet, High-Fat; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D017930:Genes, Reporter; D057809:HEK293 Cells; D006801:Humans; D050155:Lipogenesis / Q000502:physiology*; D008099:Liver / Q000166:cytology / Q000378:metabolism; D000071518:Liver X Receptors; D008297:Male; D018345:Mice, Knockout; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics / Q000378:metabolism*; D057093:Orphan Nuclear Receptors / Q000235:genetics / Q000378:metabolism*; D019308:Palmitic Acid / Q000378:metabolism / Q000494:pharmacology; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; C000605214:Nr1h3 protein, mouse; D057093:Orphan Nuclear Receptors; D019308:Palmitic Acid; C413164:PRMT3 protein, human; C502438:PRMT3 protein, mouse; D011484:Protein-Arginine N-Methyltransferases