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E3 ligase FBXW7 suppresses brown fat expansion and browning of white fat

文献类型：期刊论文

作者Yu, Jian1,8,9,10,11; Gu, Xuejiang4; Guo, Yingying3; Gao, Mingyuan9,10; Cheng, Shimiao9,10; Meng, Meiyao9,10; Cui, Xiangdi9,10; Zhang, Zhe9,10; Guo, Wenxiu9,10; Yan, Dandan3
刊名EMBO REPORTS
出版日期2025-01-02
页码20
关键词Obesity Thermogenic Fat Brown Fat Expansion Browning of White Fat Ubiquitination
ISSN号1469-221X
DOI10.1038/s44319-024-00337-w
通讯作者Xu, Lingyan(lyxu@bio.ecnu.edu.cn) ; Liu, Bin(liubin@jou.edu.cn) ; Hu, Cheng(alfredhc@sjtu.edu.cn) ; Ma, Xinran(xrma@bio.ecnu.edu.cn)
英文摘要Thermogenic fat, including brown and beige fat, dissipates heat via thermogenesis and enhances energy expenditure. Thus, its activation represents a therapeutic strategy to combat obesity. Here, we demonstrate that levels of F-box and WD repeat domain-containing 7 (FBXW7), an E3 ubiquitin protein ligase, negatively correlate with thermogenic fat functionality. FBXW7 overexpression in fat suppresses energy expenditure and thermogenesis, thus aggravates obesity and metabolic dysfunctions in mice. Conversely, FBXW7 depletion in fat leads to brown fat expansion and browning of white fat, and protects mice from diet induced obesity, hepatic steatosis, and hyperlipidemia. Mechanistically, FBXW7 binds to S6K1 and promotes its ubiquitination and proteasomal degradation, which in turn impacts glycolysis and brown preadipocyte proliferation via lactate. Besides, the beneficial metabolic effects of FBXW7 depletion in fat are attenuated by fat-specific knockdown of S6K1 in vivo. In summary, we provide evidence that adipose FBXW7 acts as a major regulator for thermogenic fat biology and energy homeostasis and serves as potential therapeutic target for obesity and metabolic diseases.
WOS关键词ADIPOSE-TISSUE ; UBIQUITIN LIGASE ; BEIGE FAT ; MTOR ; CELL ; GLUCOSE ; ADIPOCYTES ; GLYCOLYSIS ; ACTIVATION ; OBESITY
资助项目MOST | National Natural Science Foundation of China (NSFC)[32325024] ; MOST | National Natural Science Foundation of China (NSFC)[82300979] ; MOST | National Natural Science Foundation of China (NSFC)[32222024] ; MOST | National Natural Science Foundation of China (NSFC)[32271224] ; MOST | National Natural Science Foundation of China (NSFC)[32071148] ; MOST | National Natural Science Foundation of China (NSFC)[22225702] ; MOST | National Natural Science Foundation of China (NSFC)[82000802] ; National Natural Science Foundation of China[2023YFA1800400] ; National Natural Science Foundation of China[2019YFA09004500] ; National Key Research and Development Program of China[22ZR1421200] ; National Key Research and Development Program of China[21140904300] ; Science and Technology Commission of Shanghai Municipality[CSTB2022NSCQ-JQX0033] ; Natural Science Foundation of Chongqing, China[2021C03069] ; Key Research and Development Project of Zhejiang Province[LY20H070003] ; Zhejiang Provincial Natural Science Foundation of China[SHSMU-ZDCX20212700] ; Innovative research team of high-level local universities in Shanghai[2022ZZ01002] ; Shanghai Research Center for Endocrine and Metabolic Diseases[2023M741184] ; Shanghai Municipal Key Clinical Specialty, China Postdoctoral Science Foundation ; Fundamental research funds for the central universities, ECNU public platform for Innovation
WOS研究方向Biochemistry & Molecular Biology ; Cell Biology
语种英语
WOS记录号WOS:001388234800001
出版者SPRINGERNATURE
源URL[http://119.78.100.183/handle/2S10ELR8/315279]  
专题中国科学院上海药物研究所
通讯作者Xu, Lingyan; Liu, Bin; Hu, Cheng; Ma, Xinran
作者单位1.East China Normal Univ, Chongqing Inst, Chongqing Key Lab Precis Opt, Chongqing 401120, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
3.Shanghai Diabet Inst, Shanghai Clin Ctr Diabet, Shanghai Key Lab Diabet Mellitus, Shanghai 200233, Peoples R China
4.Wenzhou Med Univ, Affiliated Hosp 1, Dept Endocrine & Metab Dis, Wenzhou 325000, Zhejiang, Peoples R China
5.East China Normal Univ, Inst Aging, Shanghai 200241, Peoples R China
6.Fudan Univ, Zhongshan Hosp, Dept Endocrinol & Metab, Minist Educ,Key Lab Metab & Mol Med, Shanghai 200000, Peoples R China
7.Jiangsu Ocean Univ, Coll Pharm, Jiangsu Key Lab Marine Pharmaceut Cpd Screening, Lianyungang 222005, Peoples R China
8.Fengxian Dist Cent Hosp, Joint Ctr Translat Med, Shanghai 201400, Peoples R China
9.East China Normal Univ, Shanghai Key Lab Regulatory Biol, Inst Biomed Sci, Shanghai 200241, Peoples R China
10.East China Normal Univ, Sch Life Sci, Shanghai 200241, Peoples R China
推荐引用方式
GB/T 7714		 Yu, Jian,Gu, Xuejiang,Guo, Yingying,et al. E3 ligase FBXW7 suppresses brown fat expansion and browning of white fat[J]. EMBO REPORTS,2025:20.
APA Yu, Jian.,Gu, Xuejiang.,Guo, Yingying.,Gao, Mingyuan.,Cheng, Shimiao.,...&Ma, Xinran.(2025).E3 ligase FBXW7 suppresses brown fat expansion and browning of white fat.EMBO REPORTS,20.
MLA Yu, Jian,et al."E3 ligase FBXW7 suppresses brown fat expansion and browning of white fat".EMBO REPORTS (2025):20.

入库方式： OAI收割

来源：上海药物研究所

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