Deficiency of Both Farnesoid X Receptor and Takeda G Protein-Coupled Receptor 5 Exacerbated Liver Fibrosis in Mice.

ABSTRACT: Activation of the nuclear bile acid receptor farnesoid X receptor (FXR) protects against hepatic inflammation and injury, while Takeda G protein-coupled receptor 5 (TGR5) promotes adipose tissue browning and energy metabolism. Here, we examined the physiological and metabolic effects of the deficiency of these two bile acid receptors on hepatic metabolism and injury in mice. Fxr/Tgr5 double knockout mice (DKO) were generated for metabolic phenotyping. Male DKO mice fed a chow diet had reduced liver lipid levels but increased serum cholesterol levels. Liver cholesterol 7α-hydroxylase (Cyp7a1) activity and sterol 12α-hydroxylase mRNA levels were induced, while ileum FXR target genes were suppressed in DKO mice compared to wild-type (WT) mice. Bile acid pool size was increased in DKO mice, wi

SUBMITTER: Ferrell JM 

PROVIDER: S-EPMC6642864 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature