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Amelioration of nonalcoholic fatty liver disease by inhibiting the deubiquitylating enzyme RPN11

文献类型：期刊论文

作者Zhou, Bing11,12; Luo, Yunchen10; Bi, Hanqi12; Zhang, Ni9; Ma, Mingyue11,12; Dong, Zhixia12; Ji, Nana12; Zhang, Shuo12; Wang, Xiaoye8; Liu, Yuejun7
刊名CELL METABOLISM
出版日期2024-10-01
卷号36期号:10页码:25
ISSN号1550-4131
DOI10.1016/j.cmet.2024.07.014
通讯作者Zhao, Bing(bingzhao@fudan.edu.cn) ; Li, Yao(yao.li@shsmu.edu.cn) ; Hu, Cheng(alfredhc@sjtu.edu.cn) ; Lu, Yan(luyan5011@shsmu.edu.cn)
英文摘要Nonalcoholic fatty liver disease (NAFLD), including its more severe manifestation nonalcoholic steatohepatitis (NASH), is a global public health challenge. Here, we explore the role of deubiquitinating enzyme RPN11 in NAFLD and NASH. Hepatocyte-specific RPN11 knockout mice are protected from diet-induced liver steatosis, insulin resistance, and steatohepatitis. Mechanistically, RPN11 deubiquitinates and stabilizes METTL3 to enhance the m6A modification and expression of acyl-coenzyme A (CoA) synthetase short-chain family member 3 (ACSS3), which generates propionyl-CoA to upregulate lipid metabolism genes via histone propionylation. The RPN11-METTL3-ACSS3-histone propionylation pathway is activated in the livers of patients with NAFLD. Pharmacological inhibition of RPN11 by Capzimin ameliorated NAFLD, NASH, and related metabolic disorders in mice and reduced lipid contents in human hepatocytes cultured in 2D and 3D. These results demonstrate that RPN11 is a novel regulator of NAFLD/NASH and that suppressing RPN11 has therapeutic potential for the treatment.
WOS关键词IDENTIFICATION ; PREDICTION
资助项目National Key Research and Development Program of China[2023YFA1800803] ; National Natural Science Foundation of China[82325010] ; National Natural Science Foundation of China[92268109] ; National Natural Science Foundation of China[82300966] ; National Natural Science Foundation of China[82070887] ; National Natural Science Foundation of China[82370572] ; National Natural Science Foundation of China[82171685] ; National Natural Science Foundation of China[82270918] ; National Natural Science Foundation of China[82300961] ; Shanghai Sailing Program by the Shanghai Municipal Science and Technology Committee[22YF1432800] ; Youth Cultivation Project of Shanghai Jiao Tong University Affiliated Sixth People's Hospital[ynjq202202] ; Youth Cultivation Project of Shanghai Jiao Tong University Affiliated Sixth People's Hospital[LY33.X-3531] ; Youth Cultivation Project of Shanghai Jiao Tong University Affiliated Sixth People's Hospital[ynqn202107] ; Young Elite Scientists Sponsorship Program by CAST[2023QNRC001]
WOS研究方向Cell Biology ; Endocrinology & Metabolism
语种英语
WOS记录号WOS:001331370200001
出版者CELL PRESS
源URL[http://119.78.100.183/handle/2S10ELR8/313805]  
专题新药研究国家重点实验室
通讯作者Zhao, Bing; Li, Yao; Hu, Cheng; Lu, Yan
作者单位1.Southern Med Univ, Fengxian Cent Hosp, Inst Metab Dis, Shanghai, Peoples R China
2.Shanghai Jiao Tong Univ, Sch Med, Dept Lab Anim Sci, Shanghai, Peoples R China
3.Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Sch Med, Dept Assisted Reprod, Shanghai, Peoples R China
4.East China Normal Univ, Sch Life Sci, Shanghai, Peoples R China
5.East China Normal Univ, Inst Biomed Sci, Shanghai Key Lab Regulatory Biol, Shanghai, Peoples R China
6.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China
7.Fudan Univ, Zhongshan Hosp, Dept Endocrinol & Metab, Shanghai, Peoples R China
8.Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Shanghai, Peoples R China
9.Wenzhou Med Univ, Affiliated Hosp 1, MAFLD Res Ctr, Dept Hepatol, Wenzhou, Peoples R China
10.Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Dept Endocrinol & Metab, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Zhou, Bing,Luo, Yunchen,Bi, Hanqi,et al. Amelioration of nonalcoholic fatty liver disease by inhibiting the deubiquitylating enzyme RPN11[J]. CELL METABOLISM,2024,36(10):25.
APA Zhou, Bing.,Luo, Yunchen.,Bi, Hanqi.,Zhang, Ni.,Ma, Mingyue.,...&Lu, Yan.(2024).Amelioration of nonalcoholic fatty liver disease by inhibiting the deubiquitylating enzyme RPN11.CELL METABOLISM,36(10),25.
MLA Zhou, Bing,et al."Amelioration of nonalcoholic fatty liver disease by inhibiting the deubiquitylating enzyme RPN11".CELL METABOLISM 36.10(2024):25.

入库方式： OAI收割

来源：上海药物研究所

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