FXR deficiency alters bile acid pool composition and exacerbates chronic alcohol induced liver injury.

ABSTRACT: Recent studies have investigated the roles of FXR deficiency in the pathogenesis of alcoholic liver disease (ALD). However, the underlying molecular mechanisms remain unclear. In this study, FXR knockout (FXR^-/-) and wild-type (WT) mice were subjected to chronic-plus-binge alcohol feeding to study the effect of FXR deficiency on ALD development. The degree of liver injury was greater in FXR^-/- mice compared to WT mice. Ethanol feeding enhanced hepatic steatosis in FXR^-/- mice, accompanied by decreased mRNA levels of Pparα and Srebp-1c. The expression of Lcn2 was increased by ethanol treatment, despite unchanged expression of pro-inflammatory cytokines Tnfα, Il6 and Il-1β. Furthermore, ethanol treatment altered bile acid (BA) homeostasis to a greater extent

SUBMITTER: Kong B 

PROVIDER: S-EPMC6451669 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature