Aquaporin-8 ameliorates hepatic steatosis through farnesoid X receptor in obese mice

被引：5
作者：
Xiang, Minqi [1 ,2 ]
Qian, Xu [1 ,2 ]
Han, Luyu [3 ]
Wang, Hui [1 ,2 ]
Wang, Jiqiu [1 ,2 ]
Liu, Weiren [4 ]
Gu, Yanyun [1 ,2 ]
Yao, Shuangshuang [5 ]
Yang, Jian [1 ,2 ]
Zhang, Yifei [1 ,2 ]
Peng, Ying [1 ,2 ]
Zhang, Zhiguo [1 ,2 ]
机构：
[1] Shanghai Jiao Tong Univ, Ruijin Hosp, Shanghai Inst Endocrine & Metab Dis, Sch Med,Dept Endocrine & Metab Dis, Shanghai, Peoples R China
[2] Shanghai Jiao Tong Univ, Ruijin Hosp, Shanghai Natl Clin Res Ctr Metab Dis, Sch Med,Key Lab Endocrine & Metab Dis,Natl Hlth Co, Shanghai, Peoples R China
[3] Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Nutr & Hlth, Shanghai, Peoples R China
[4] Fudan Univ, Zhongshan Hosp, Liver Canc Inst, Dept Liver Surg & Transplantat,Key Lab Carcinogene, Shanghai, Peoples R China
[5] Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Sch Med, Dept Endocrinol & Metab, Shanghai, Peoples R China
来源：
ISCIENCE | 2023年 / 26卷 / 04期
基金：
中国国家自然科学基金;
关键词：
BILE-ACID METABOLISM; WATER CHANNELS; NONALCOHOLIC STEATOHEPATITIS; HEPATOCYTE AQUAPORIN-8; OBETICHOLIC ACID; RAT HEPATOCYTES; LIVER; MEMBRANE; TARGETS; CHOLESTEROL;
D O I：
10.1016/j.isci.2023.106561
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
Aquaporin-8(AQP8), is a transmembrane channel protein that abounds in liver, which mainly promotes water transport, modulating bile acid formation. However, its role in hepatic lipid metabolism remains unclear. In this study, we found the expression of AQP8 was reduced in liver specimens of patients with NAFLD, high-fat diet (HFD)-induced mice and genetically obese db/db mice. Knockdown of AQP8 in hepatocytes exacerbated the intracellular lipid accumulation induced by free fatty acid (FFA) mixtures. In contrast, hepatic AQP8 overexpression activated farnesoid X receptor (FXR), inhibiting gene expression associated with lipogenesis, which further reduced intrahepatic triglyceride overload in obese mice. FXR knockout abrogated the ameliorating effect of AQP8 overexpression on NAFLD in mice. These findings indicate that AQP8 overexpression protects against fatty liver through activating the FXR pathway.
引用
收藏
页数：19
相关论文
共 50 条
  • [1] Yin Yang 1 promotes hepatic steatosis through repression of farnesoid X receptor in obese mice
    Lu, Yan
    Ma, Zhimin
    Zhang, Zhijian
    Xiong, Xuelian
    Wang, Xiaolin
    Zhang, Huijie
    Shi, Guojun
    Xia, Xuefeng
    Ning, Guang
    Li, Xiaoying
    GUT, 2014, 63 (01) : 170 - 177
  • [2] Cycloastragenol improves hepatic steatosis by activating farnesoid X receptor signalling
    Gu, Ming
    Zhang, Shiying
    Zhao, Yuanyuan
    Huang, Jinwen
    Wang, Yahui
    Li, Yin
    Fan, Shengjie
    Yang, Li
    Ji, Guang
    Tong, Qingchun
    Huang, Cheng
    PHARMACOLOGICAL RESEARCH, 2017, 121 : 22 - 32
  • [3] Inhibiting Glycosphingolipid Synthesis Ameliorates Hepatic Steatosis in Obese Mice
    Zhao, Hongmei
    Przybylska, Malgorzata
    Wu, I-Huan
    Zhang, Jinhua
    Maniatis, Panagiotis
    Pacheco, Joshua
    Piepenhagen, Peter
    Copeland, Diane
    Arbeeny, Cynthia
    Shayman, James A.
    Aerts, Johannes M.
    Jiang, Canwen
    Cheng, Seng H.
    Yew, Nelson S.
    HEPATOLOGY, 2009, 50 (01) : 85 - 93
  • [4] Cholesterol Can Modulate Mitochondrial Aquaporin-8 Expression in Human Hepatic Cells
    Danielli, Mauro
    Capiglioni, Alejo M.
    Marrone, Julieta
    Calamita, Giuseppe
    Marinelli, Raul A.
    IUBMB LIFE, 2017, 69 (05) : 341 - 346
  • [5] Farnesoid X receptor mediates hepatic steatosis induced by PM2.5
    Wang, Mengyao
    Tan, Jieqiong
    Zhou, Ji
    Yi, Bin
    Huang, Zhijun
    ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH, 2020, 27 (27) : 34412 - 34420
  • [6] Rilmenidine improves hepatic steatosis through p38-dependent pathway to higher the expression of farnesoid X receptor
    Yang, Po-Sheng
    Wu, Hung-Tsung
    Chung, Hsien-Hui
    Chen, Chun-Ta
    Chi, Chin-Wen
    Yeh, Ching-Hua
    Cheng, Juei-Tang
    NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 2012, 385 (01) : 51 - 56
  • [7] Glucocorticoids Promote Hepatic Cholestasis in Mice by Inhibiting the Transcriptional Activity of the Farnesoid X Receptor
    Lu, Yan
    Zhang, Zhijian
    Xiong, Xuelian
    Wang, Xiaolin
    Li, Jin
    Shi, Guojun
    Yang, Jian
    Zhang, Xianfeng
    Zhang, Huijie
    Hong, Jie
    Xia, Xuefeng
    Ning, Guang
    Li, Xiaoying
    GASTROENTEROLOGY, 2012, 143 (06) : 1630 - +
  • [8] Punicalagin alleviates hypercholesterolemia in mice through modulating farnesoid X receptor signaling and modulating gut microbiota
    Liu, Huanhuan
    Liu, Hongli
    Yan, Chunhong
    Liu, Jiaxiu
    Cao, Yu
    Li, Guopeng
    Xia, Xiaodong
    FOOD SCIENCE AND HUMAN WELLNESS, 2025, 14 (01)
  • [9] Ginkgolide B lowers body weight and ameliorates hepatic steatosis in high-fat diet-induced obese mice correlated with pregnane X receptor activation
    Luo, Lingling
    Li, Yin
    Wang, Dongshan
    Zhao, Yuanyuan
    Wang, Yahui
    Li, Fei
    Fang, Jinan
    Chen, Hui
    Fan, Shengjie
    Huang, Cheng
    RSC ADVANCES, 2017, 7 (60) : 37858 - 37866
  • [10] Genomic analysis of hepatic farnesoid X receptor binding sites reveals altered binding in obesity and direct gene repression by farnesoid X receptor in mice
    Lee, Jiyoung
    Seok, Sunmi
    Yu, Pengfei
    Kim, Kyungsu
    Smith, Zachary
    Rivas-Astroza, Marcelo
    Zhong, Sheng
    Kemper, Jongsook Kim
    HEPATOLOGY, 2012, 56 (01) : 108 - 117
12345