Activation of farnesoid X receptor attenuates hepatic injury in a murine model of alcoholic liver disease
Activation of farnesoid X receptor attenuates hepatic injury in a murine model of alcoholic liver disease
复制标题
法尼醇 X 受体的激活可减轻酒精性肝病小鼠模型中的肝损伤
DOI：
10.1016/j.bbrc.2013.11.057
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发表时间：
2014-01-03
影响因子：
3.1
通讯作者：
Gu, Jianxin
中科院分区：
文献类型：
--
作者：
Wu, Weibin;Zhu, Bo;Gu, Jianxin
Alcoholic liver disease (ALD) is a common cause of advanced liver disease, and considered as a major risk factor of morbidity and mortality worldwide. Hepatic cholestasis is a pathophysiological feature observed in all stages of ALD. The farnesoid X receptor (FXR) is a member of the nuclear hormone receptor superfamily, and plays an essential role in the regulation of bile acid, lipid and glucose homeostasis. However, the role of FXR in the pathogenesis and progression of ALD remains largely unknown. Mice were fed Lieber-DeCarli ethanol diet or an isocaloric control diet. We used a specific agonist of FXR WAY-362450 to study the effect of pharmacological activation of FXR in alcoholic liver disease. In this study, we demonstrated that FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. Activation of FXR by specific agonist WAY-362450 protected mice from the development of ALD. We also found that WAY-362450 treatment rescued FXR activity, suppressed ethanol-induced Cyp2e1 up-regulation and attenuated oxidative stress in liver. Our results highlight a key role of FXR in the modulation of ALD development, and propose specific FXR agonists for the treatment of ALD patients. (C) 2013 Elsevier Inc. All rights reserved.
