PRMT3 Regulates Hepatic Lipogenesis Through Direct Interaction With LXRα

被引:37
作者
Kim, Dong-il [1 ]
Park, Min-jung [1 ]
Lim, Seul-ki [2 ]
Park, Jae-il [3 ]
Yoon, Kyung-chul [4 ]
Han, Ho-jae [5 ]
Gustafsson, Jan-Ake [6 ,7 ]
Lim, Jae-hyang [8 ]
Park, Soo-hyun [1 ]
机构
[1] Chonnam Natl Univ, Coll Vet Med, Kwangju, South Korea
[2] World Inst Kimchi, R&D Div, Metab & Funct Res Grp, Kwangju, South Korea
[3] Chonnam Natl Univ, Gwangju Ctr, Korea Basic Sci Inst, Kwangju, South Korea
[4] Chonnam Natl Univ, Med Sch & Hosp, Dept Ophthalmol, Kwangju, South Korea
[5] Seoul Natl Univ, Coll Vet Med, Dept Verterinary Physiol, Seoul, South Korea
[6] Karolinska Inst, Dept Biosci & Nutr, Mol Nutr Unit, Stockholm, Sweden
[7] Univ Houston, Ctr Nucl Receptors & Cell Signaling, Houston, TX USA
[8] Ewha Womans Univ, Sch Med, Dept Microbiol, Seoul, South Korea
基金
新加坡国家研究基金会;
关键词
LIVER-X-RECEPTOR; HIGH-FAT DIET; ARGININE METHYLATION; INSULIN-RESISTANCE; GENE-EXPRESSION; PROTEIN; MICE; METABOLISM; ACTIVATION; METHYLTRANSFERASE;
D O I
10.2337/db13-1394
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 a (LXR alpha). Thus we examined the pathophysiological role of PRMTs in NAFLD and their relationship with LXR alpha. 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 LXR alpha by directly binding with LXR alpha in a methylation-independent manner. In addition, PA treatment translocated PRMT3 to the nucleus. In animal models, a high-fat diet increased the LXR alpha and PRMT3 expressions and binding, which was not observed in LXR alpha KO mice. Furthermore, increased PRMT3 expression and its binding with LXR alpha were observed in NAFLD patients. Taken together, LXR alpha and PRMT3 expression was increased in cellular and mouse models of NAFLD and human patients, and PRMT3 translocated into the nucleus bound with LXR alpha as a transcriptional cofactor, which induced lipogenesis. In conclusion, PRMT3 translocation by PA is coupled to the binding of LXR alpha, which is responsible for the onset of fatty liver.
引用
收藏
页码:60 / 71
页数:12
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