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Hyodeoxycholic acid ameliorates nonalcoholic fatty liver disease by inhibiting RAN-mediated PPARa nucleus-cytoplasm shuttling

文献类型：期刊论文

作者Zhong, Jing7,8; He, Xiaofang8; Gao, Xinxin8; Liu, Qiaohong6; Zhao, Yu6; Hong, Ying8; Zhu, Weize8; Yan, Juan8; Li, Yifan8; Li, Yan8
刊名NATURE COMMUNICATIONS
出版日期2023-09-06
卷号14期号:1页码:18
DOI10.1038/s41467-023-41061-8
通讯作者Xie, Cen(xiecen@simm.ac.cn) ; Hu, Yiyang(yyhuliver@163.com) ; Sheng, Lili(llsheng@shutcm.edu.cn) ; Li, Houkai(hk_li@shutcm.edu.cn)
英文摘要Nonalcoholic fatty liver disease (NAFLD) is usually characterized with disrupted bile acid (BA) homeostasis. However, the exact role of certain BA in NAFLD is poorly understood. Here we show levels of serum hyodeoxycholic acid (HDCA) decrease in both NAFLD patients and mice, as well as in liver and intestinal contents of NAFLD mice compared to their healthy counterparts. Serum HDCA is also inversely correlated with NAFLD severity. Dietary HDCA supplementation ameliorates diet-induced NAFLD in male wild type mice by activating fatty acid oxidation in hepatic peroxisome proliferator-activated receptor & alpha; (PPAR & alpha;)-dependent way because the anti-NAFLD effect of HDCA is abolished in hepatocyte-specific Ppar & alpha; knockout mice. Mechanistically, HDCA facilitates nuclear localization of PPAR & alpha; by directly interacting with RAN protein. This interaction disrupts the formation of RAN/CRM1/PPAR & alpha; nucleus-cytoplasm shuttling heterotrimer. Our results demonstrate the therapeutic potential of HDCA for NAFLD and provide new insights of BAs on regulating fatty acid metabolism. Nonalcoholic fatty liver disease (NAFLD) is often linked to disrupted bile acid homeostasis. Here, the authors show hyodeoxycholic acid (HDCA) ameliorates nonalcoholic fatty liver disease by inhibiting the formation of RAN/CRM1/PPAR & alpha; nuclear export heterotrimer, resulting in increased nuclear localization of PPAR & alpha; and activated fatty acid oxidation.
WOS关键词BILE-ACIDS ; ACTIVATED RECEPTORS ; ALPHA ; INFLAMMATION ; MICE ; CHOLESTEROL ; METABOLISM ; EXPORT ; STEATOHEPATITIS ; HOMEOSTASIS
资助项目National Natural Science Foundation of China[U21A20413] ; National Natural Science Foundation of China[82273624] ; National Natural Science Foundation of China[82222071] ; Clinical Research Plan of SHDC[SHDC2020CR2049B] ; Natural Science Foundation of Shanghai[20ZR1453900] ; Shanghai Excellent Academic Leaders Program[21XD1403500] ; SIMM-SHUTCM Traditional Chinese Medicine Innovation Joint Research Program (2022)[E2G807H] ; Shanghai Municipal Science and Technology Major Project
WOS研究方向Science & Technology - Other Topics
语种英语
出版者NATURE PORTFOLIO
WOS记录号WOS:001066569000016
源URL[http://119.78.100.183/handle/2S10ELR8/307260]  
专题新药研究国家重点实验室
通讯作者Xie, Cen; Hu, Yiyang; Sheng, Lili; Li, Houkai
作者单位1.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
2.Hong Kong Baptist Univ, Sch Chinese Med, Kowloon Tong, Hong Kong 999077, Peoples R China
3.Shanghai Jiao Tong Univ, Dept Otorhinolaryngol, Shanghai Peoples Hosp 6, Sch Med, Shanghai 200233, Peoples R China
4.Shanghai Univ Tradit Chinese Med, Inst Interdisciplinary Integrat Med Res, Shanghai 201203, Peoples R China
5.Univ Calif Davis, Dept Dermatol, Sch Med, Sacramento, CA USA
6.Shanghai Univ Tradit Chinese Med, Shuguang Hosp, Inst Liver Dis, Key Lab Liver & Kidney Dis Minist Educ, Shanghai 201203, Peoples R China
7.Zhejiang Univ, Affiliated Huzhou Hosp, Sch Med, Huzhou Key Lab Precis Med Res & Translat Infect Di, Huzhou 313000, Peoples R China
8.Shanghai Univ Tradit Chinese Med, Sch Pharm, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Zhong, Jing,He, Xiaofang,Gao, Xinxin,et al. Hyodeoxycholic acid ameliorates nonalcoholic fatty liver disease by inhibiting RAN-mediated PPARa nucleus-cytoplasm shuttling[J]. NATURE COMMUNICATIONS,2023,14(1):18.
APA Zhong, Jing.,He, Xiaofang.,Gao, Xinxin.,Liu, Qiaohong.,Zhao, Yu.,...&Li, Houkai.(2023).Hyodeoxycholic acid ameliorates nonalcoholic fatty liver disease by inhibiting RAN-mediated PPARa nucleus-cytoplasm shuttling.NATURE COMMUNICATIONS,14(1),18.
MLA Zhong, Jing,et al."Hyodeoxycholic acid ameliorates nonalcoholic fatty liver disease by inhibiting RAN-mediated PPARa nucleus-cytoplasm shuttling".NATURE COMMUNICATIONS 14.1(2023):18.

入库方式： OAI收割

来源：上海药物研究所

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