Bile acids: Natural ligands for an orphan nuclear receptor

Bile acids regulate the transcription of genes that control cholesterol hom eostasis through molecular mechanisms that are poorly understood. Physiolog ical concentrations of free and conjugated chenodeoxycholic acid, Lithochol ic acid, and deoxycholic acid activated the farnesoid X receptor (FXR; NR1H 4), an orphan nuclear receptor. As Ligands, these bile acids and their conj ugates modulated interaction of FXR with a peptide derived from steroid rec eptor coactivator 1. These results provide evidence for a nuclear bile acid signaling pathway that may regulate cholesterol homeostasis.