American Diabetes Association
Revised Supplemental Material.pdf (4.85 MB)

PRMT4 facilitates white adipose tissue browning and thermogenesis by methylating PPARγ

Download (4.85 MB)
posted on 2023-06-02, 15:15 authored by Yi Zhong, Yilong Wang, Xiaoguang Li, Haojie Qin, Shu Yan, Caijun Rao, Di Fan, Duqiu Liu, Fei Deng, Yanli Miao, Ling Yang, Kai Huang

Obesity is a global health threat, and the induction of white adipose tissue (WAT) browning presents a promising therapeutic method for it. Recent publications revealed the essential role of protein arginine methyltransferase 4 (PRMT4) in lipid metabolism and adipogenesis, but its involvement in WAT browning has not been investigated. Our initial studies found that the expression of PRMT4 in adipocytes was upregulated in cold-induced WAT browning but downregulated in obesity. Besides, PRMT4 overexpression in inguinal adipose tissue accelerated WAT browning and thermogenesis to protect against high-fat diet (HFD)-induced obesity and metabolic disruptions. Mechanistically, our work demonstrated that PRMT4 methylated peroxisome proliferator-activated receptor-γ (PPARγ) on Arg240 to enhance its interaction with the co-activator PR domain-containing protein 16 (PRDM16), leading to the increased expression of thermogenic genes. Taken together, our results uncover the essential role of PRMT4/PPARγ/PRDM16 axis in the pathogenesis of WAT browning.


This work was supported by National Natural Science Foundation of China [grant numbers 81801062, 81974078, 81570530 and 81370550] and Natural Science Foundation of Hubei Province [grant numbers 2019ACA133].