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Farnesoid X receptor is an important target for the treatment of disorders of bile acid and fatty acid metabolism in mice with nonalcoholic fatty liver disease combined with cholestasis

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资源类型：
Pubmed体系：
作者：
Liu Xinzhu[1,2] * ; Wang Jiaxuan[1] * ; Li Maogang[3] ; Qiu Jiannan[1] ; Li Xingying[4] ; Qi Li[1] ; Liu Jia[1] ; Liu Ping[1,2,*1] ; Xie Guoxiang[3,5,*2] ; Wang Xiaoning[1,*1] ;
机构： [1]Basic Research Center of Traditional Chinese Medicine Prescription and Syndrome, Institute of Interdisciplinary Science, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. [2]Institute of Liver Disease, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. [3]Human Metabolomics Institute, Inc., Shenzhen, 518109, Guangdong, China. [4]South China Normal University, Guangzhou, 510631, Guangdong, China. [5]Faculty of Food Science and Engineering, Kunming University of Science and Technology, Kunming, 650500, China.
出处：
DOI： 10.1111/jgh.16279
ISSN：

关键词： Alpha-naphthylisothiocyanate Bile acid Cholestasis Farnesoid X receptor Fatty acid Nonalcoholic fatty liver disease

摘要：
The prevalence of nonalcoholic fatty liver disease (NAFLD) has been rising globally. NAFLD patients combined with cholestasis have more obvious liver fibrosis, impaired bile acid (BA), and fatty acid (FA) metabolism and severer liver injury; however, its therapeutic options are limited, and the underlying metabolic mechanisms are understood. Here, we aimed to investigate the effects of farnesoid X receptor (FXR) on BA and FA metabolism in NAFLD combined with cholestasis and related signaling pathways.A mouse model of NAFLD combined with cholestasis was established by joint intervention with high-fat diet (HFD) and alpha-naphthylisothiocyanate. The effects of FXR on BA and FA metabolism were evaluated by serum biochemical analysis. Liver damage was identified by histopathology. The expression of nuclear hormone receptor, membrane receptor, FA transmembrane transporter, and BA transporter protein in mice were measured by western blot.NAFLD mice combined with cholestasis developed more severe cholestasis and dysregulated BA and FA metabolism. Meanwhile, the expression of FXR protein was decreased in NAFLD mice combined with cholestasis compared to the controls. Fxr-/- mice showed liver injury. HFD aggravated the liver injury with decreased BSEP expression, increased expression of NTCP, LXRα, SREBP-1c, FAS, ACC1, and CD36, and significantly increased BA and FA accumulation.All the results suggested that FXR plays a key role in both FA and BA metabolism in NAFLD combined with cholestasis and thus may be a potential target for the treatment of disorders of BA and FA metabolism in NAFLD combined with cholestasis.© 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2022]版：
大类 | 3 区 医学
小类 | 3 区 胃肠肝病学
最新[2025]版：
大类 | 3 区 医学
小类 | 3 区 胃肠肝病学
第一作者：
第一作者机构： [1]Basic Research Center of Traditional Chinese Medicine Prescription and Syndrome, Institute of Interdisciplinary Science, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. [2]Institute of Liver Disease, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
共同第一作者：
通讯作者：
通讯机构： [1]Basic Research Center of Traditional Chinese Medicine Prescription and Syndrome, Institute of Interdisciplinary Science, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. [2]Institute of Liver Disease, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. [3]Human Metabolomics Institute, Inc., Shenzhen, 518109, Guangdong, China. [5]Faculty of Food Science and Engineering, Kunming University of Science and Technology, Kunming, 650500, China. [*1]Basic Research Center of Traditional Chinese Medicine Prescription and Syndrome, Institute of Interdisciplinary Science, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. [*2]Human Metabolomics Institute, Inc., Shenzhen, Guangdong 518109, China.
推荐引用方式(GB/T 7714)：
Liu Xinzhu,Wang Jiaxuan,Li Maogang,et al.Farnesoid X receptor is an important target for the treatment of disorders of bile acid and fatty acid metabolism in mice with nonalcoholic fatty liver disease combined with cholestasis[J].Journal of gastroenterology and hepatology.2023,doi:10.1111/jgh.16279.
APA：
Liu Xinzhu,Wang Jiaxuan,Li Maogang,Qiu Jiannan,Li Xingying...&Wang Xiaoning.(2023).Farnesoid X receptor is an important target for the treatment of disorders of bile acid and fatty acid metabolism in mice with nonalcoholic fatty liver disease combined with cholestasis.Journal of gastroenterology and hepatology,,
MLA：
Liu Xinzhu,et al."Farnesoid X receptor is an important target for the treatment of disorders of bile acid and fatty acid metabolism in mice with nonalcoholic fatty liver disease combined with cholestasis".Journal of gastroenterology and hepatology .(2023)

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