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.
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页数：19
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