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PRMT4 facilitates white adipose tissue browning and thermogenesis by methylating PPARγ

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单位： [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.

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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.© 2023 by the American Diabetes Association.

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出版当年[2022]版：

大类 | 1 区

医学

小类 | 1 区内分泌学与代谢

最新[2025]版：

大类 | 2 区

医学

小类 | 2 区内分泌学与代谢

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出版当年[2021]版：

Q1 ENDOCRINOLOGY & METABOLISM

最新[2023]版：

Q1 ENDOCRINOLOGY & METABOLISM

影响因子： 6.2 最新[2023版] 7.1 最新五年平均 9.305 出版当年[2021版] 10.493 出版当年五年平均 9.461 出版前一年[2020版] 7.7 出版后一年[2022版]

第一作者：

第一作者单位： [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.

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通讯机构： [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. [4]Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. [9]Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. [*1]Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, 1 Jianshe Dong Lu, Zhengzhou, 450000, China [*2]Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Ave, Wuhan, 430022, China [*3]Clinical Center for Human Genomic Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Ave, Wuhan, 430022, China

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