Obeticholic Acid Induces Hepatoxicity Via FXR in the NAFLD Mice.

ABSTRACT: Objective: Obeticholic acid (OCA), a potent farnesoid X receptor (FXR) agonist, is a promising drug for nonalcoholic fatty liver disease (NAFLD); however, it can cause liver injury, especially at high doses. Here, we investigated the role of FXR in the high-dose OCA-induced hepatoxicity in the condition of the NAFLD mouse model. Methods: Wild-type (WT) mice and FXR^-/- mice were administered with over-dose OCA (0.40%) and high-dose OCA (0.16%), in a high-fat diet. RNA-seq on liver samples of mice fed with high-dose OCA was performed to dig out the prominent biological events contributing to hepatic fibrosis. Results: Over-dose OCA induced liver injury and shortened survival in WT mice, but not FXR^-/- mice. High-dose OCA caused hepatic stellate cell

SUBMITTER: Lin C 

PROVIDER: S-EPMC9124937 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature