TY - JOUR AU - Li-Hawkins, Jia AU - Gåfvels, Mats AU - Olin, Maria AU - Lund, Erik G. AU - Andersson, Ulla AU - Schuster, Gertrud AU - Björkhem, Ingemar AU - Russell, David W. AU - Eggertsen, Gosta T1 - Cholic acid mediates negative feedback regulation of bile acid synthesis in mice PY - 2002/10/15/ AB - Cholesterol is converted into dozens of primary and secondary bile acids through pathways subject to negative feedback regulation mediated by the nuclear receptor farnesoid X receptor (FXR) and other effectors. Disruption of the sterol 12α-hydroxylase gene (Cyp8b1) in mice prevents the synthesis of cholate, a primary bile acid, and its metabolites. Feedback regulation of the rate-limiting biosynthetic enzyme cholesterol 7α-hydroxylase (CYP7A1) is lost in Cyp8b1–/– mice, causing expansion of the bile acid pool and alterations in cholesterol metabolism. Expression of other FXR target genes is unaltered in these mice. Cholate restores CYP7A1 regulation in vivo and in vitro. The results implicate cholate as an important negative regulator of bile acid synthesis and provide preliminary evidence for ligand-specific gene activation by a nuclear receptor. JF - The Journal of Clinical Investigation JA - J Clin Invest SN - 0021-9738 DO - 10.1172/JCI16309 VL - 110 IS - 8 UR - https://doi.org/10.1172/JCI16309 SP - 1191 EP - 1200 PB - The American Society for Clinical Investigation ER -