2. Academic Validation
  3. PRMT4 Facilitates White Adipose Tissue Browning and Thermogenesis by Methylating PPARγ

PRMT4 Facilitates White Adipose Tissue Browning and Thermogenesis by Methylating PPARγ

  • Diabetes. 2023 Aug 1;72(8):1095-1111. doi: 10.2337/db22-1016.
Yi Zhong 1 2,  Yilong Wang 3,  Xiaoguang Li 1,  Haojie Qin 1 4,  Shu Yan 5,  Caijun Rao 6,  Di Fan 1 4,  Duqiu Liu 1 7,  Fei Deng 8,  Yanli Miao 9,  Ling Yang 1 2,  Kai Huang 1 4 10 11
Affiliations

Affiliations

  • 1 Clinic Center of Human Gene Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 2 Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 3 Department of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
  • 4 Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 5 Heart Center and Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • 6 Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 7 Liyuan Cardiovascular Center, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 8 Department of Urology, The Second Xiangya Hospital, Central South University, Hunan, China.
  • 9 Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
  • 10 Hubei Key Laboratory of Metabolic Abnormalities and Vascular Aging, Huazhong University of Science and Technology, Wuhan, China.
  • 11 Hubei Clinical Research Center of Metabolic and Cardiovascular Disease, Huazhong University of Science and Technology,Wuhan, China.
PMID: 37216643 DOI: 10.2337/db22-1016
Abstract

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-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 coactivator PR domain-containing protein 16 (PRDM16), leading to the increased expression of thermogenic genes. Taken together, our results uncover the essential role of the PRMT4/PPARγ/PRDM16 axis in the pathogenesis of WAT browning.

Article highlights: Protein arginine methyltransferase 4 (PRMT4) expression was upregulated during cold exposure and negatively correlated with body mass of mice and humans. PRMT4 overexpression in inguinal white adipose tissue of mice improved high-fat diet-induced obesity and associated metabolic impairment due to enhanced heat production. PRMT4 methylated peroxisome proliferator-activated receptor-γ on Arg240 and facilitated the binding of the coactivator PR domain-containing protein 16 to initiate adipose tissue browning and thermogenesis. PRMT4-dependent methylation of peroxisome proliferator-activated receptor-γ on Arg240 is important in the process of inguinal white adipose tissue browning.

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