Protein Arginine Methyltransferase PRMT5 Regulates Fatty Acid Metabolism and Lipid Droplet Biogenesis in White Adipose Tissues

被引：28

作者：

Jia, Zhihao ^{[1
]}

Yue, Feng ^{[1
]}

Chen, Xiyue ^{[1
]}

Narayanan, Naagarajan ^{[2
,3
]}

Qiu, Jiamin ^{[1
]}

Syed, Sabriya A. ^{[4
]}

Imbalzano, Anthony N. ^{[4
]}

Deng, Meng ^{[2
,3
]}

Yu, Peng ^{[5
,6
]}

Hu, Changdeng ^{[7
,8
]}

Kuang, Shihuan ^{[1
,8
]}

机构：

[1] Purdue Univ, Dept Anim Sci, W Lafayette, IN 47907 USA

[2] Purdue Univ, Dept Agr & Biol Engn, W Lafayette, IN 47907 USA

[3] Purdue Univ, Bindley Biosci Ctr, W Lafayette, IN 47907 USA

[4] Univ Massachusetts, Dept Biochem & Mol Pharmacol, Sch Med, Worcester, MA 01605 USA

[5] Sichuan Univ, West China Hosp, West China Biomed Big Data Ctr, Chengdu 610041, Peoples R China

[6] Sichuan Univ, Med Big Data Ctr, Chengdu 610041, Peoples R China

[7] Purdue Univ, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA

[8] Purdue Univ Ctr Canc Res, W Lafayette, IN 47907 USA

来源：

ADVANCED SCIENCE | 2020年 / 7卷 / 23期

基金：

美国国家卫生研究院; 美国食品与农业研究所;

关键词：

BSCL2; lipodystrophy; methylation; type; 2; diabetes; adipocytes; DE-NOVO LIPOGENESIS; READ ALIGNMENT; SEIPIN; METHYLATION; LIPODYSTROPHY; INFLAMMATION; PPAR-GAMMA-2; ACTIVATION; ADIPOCYTES; EXPRESSION;

D O I：

10.1002/advs.202002602

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The protein arginine methyltransferase 5 (PRMT5) is an emerging regulator of cancer and stem cells including adipogenic progenitors. Here, a new physiological role of PRMT5 in adipocytes and systemic metabolism is reported. Conditional knockout mice were generated to ablate thePrmt5gene specifically in adipocytes (Prmt5(AKO)). The Prmt5(AKO)mice exhibit sex- and depot-dependent progressive lipodystrophy that is more pronounced in females and in visceral (than subcutaneous) white fat. The lipodystrophy and associated energy imbalance, hyperlipidemia, hepatic steatosis, glucose intolerance, and insulin resistance are exacerbated by high-fat-diet. Mechanistically, Prmt5 methylates and releases the transcription elongation factor SPT5 from Berardinelli-Seip congenital lipodystrophy 2 (Bscl2, encoding Seipin) promoter, and Prmt5(AKO)disrupts Seipin-mediated lipid droplet biogenesis. Prmt5 also methylates Sterol Regulatory Element-Binding Transcription Factor 1a (SREBP1a) and promotes lipogenic gene expression, and Prmt5(AKO)suppresses SREBP1a-dependent fatty acid metabolic pathways in adipocytes. Thus, PRMT5 plays a critical role in regulating lipid metabolism and lipid droplet biogenesis in adipocytes.

引用

页数：18

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