Secondary (iso)BAs cooperate with endogenous ligands to activate FXR under physiological and pathological conditions.

ABSTRACT: IsoBAs, stereoisomers of primary and secondary BAs, are found in feces and plasma of human individuals. BA signaling via the nuclear receptor FXR is crucial for regulation of hepatic and intestinal physiology/pathophysiology.

Aim

Investigate the ability of BA-stereoisomers to bind and modulate FXR under physiological/pathological conditions.

Methods

Expression-profiling, luciferase-assays, fluorescence-based coactivator-association assays, administration of (iso)-BAs to WT and cholestatic mice.

Results

Compared to CDCA/isoCDCA, administration of DCA/isoDCA, UDCA/isoUDCA only slightly increased mRNA expression of FXR target genes; the induction was more evident looking at pre-mRNAs. Notably, almost 50% of isoBAs were metabolized to 3-oxo-BAs within 4 h in cell-based ass

SUBMITTER: Zaufel A 

PROVIDER: S-EPMC8177068 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature