Glycine-β-muricholic acid antagonizes the intestinal farnesoid X receptor-ceramide axis and ameliorates NASH in mice.

ABSTRACT: Nonalcoholic steatohepatitis (NASH) is a rapidly developing pathology around the world, with limited treatment options available. Some farnesoid X receptor (FXR) agonists have been applied in clinical trials for NASH, but side effects such as pruritus and low-density lipoprotein elevation have been reported. Intestinal FXR is recognized as a promising therapeutic target for metabolic diseases. Glycine-β-muricholic acid (Gly-MCA) is an intestine-specific FXR antagonist previously shown to have favorable metabolic effects on obesity and insulin resistance. Herein, we identify a role for Gly-MCA in the pathogenesis of NASH, and explore the underlying molecular mechanism. Gly-MCA improved lipid accumulation, inflammatory response, and collagen deposition in two different NASH models. Mechanist

SUBMITTER: Jiang J 

PROVIDER: S-EPMC9701488 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature