Manley Sharon, Ding Wenxing
Department of Pharmacology, Toxicology and Therapeutics, the University of Kansas Medical Center, Kansas City, KS 66160, USA.
Acta Pharm Sin B. 2015 Mar;5(2):158-67. doi: 10.1016/j.apsb.2014.12.011. Epub 2015 Mar 9.
Alcoholic liver disease (ALD) is one of the major causes of liver morbidity and mortality worldwide. Chronic alcohol consumption leads to development of liver pathogenesis encompassing steatosis, inflammation, fibrosis, cirrhosis, and in extreme cases, hepatocellular carcinoma. Moreover, ALD may also associate with cholestasis. Emerging evidence now suggests that farnesoid X receptor (FXR) and bile acids also play important roles in ALD. In this review, we discuss the effects of alcohol consumption on FXR, bile acids and gut microbiome as well as their impacts on ALD. Moreover, we summarize the findings on FXR, FoxO3a (forkhead box-containing protein class O3a) and PPARα (peroxisome proliferator-activated receptor alpha) in regulation of autophagy-related gene transcription program and liver injury in response to alcohol exposure.
酒精性肝病(ALD)是全球肝脏发病和死亡的主要原因之一。长期饮酒会导致肝脏发病机制的发展,包括脂肪变性、炎症、纤维化、肝硬化,在极端情况下还会导致肝细胞癌。此外,ALD还可能与胆汁淤积有关。现在新出现的证据表明,法尼酯X受体(FXR)和胆汁酸在ALD中也发挥着重要作用。在这篇综述中,我们讨论了饮酒对FXR、胆汁酸和肠道微生物群的影响,以及它们对ALD的影响。此外,我们总结了关于FXR、FoxO3a(含叉头框蛋白O3a)和PPARα(过氧化物酶体增殖物激活受体α)在调节自噬相关基因转录程序和酒精暴露后肝损伤方面的研究结果。