Fig. 1.

WAY-362450 requires FXR for CYP8B1 repression and regulation of bile acid pool composition. A: C57BL/6J wild-type (gray bars) or FXR^−/− mice (black bars) on a standard chow diet were treated by daily oral gavage with vehicle (−) or 30 mg/kg WAY-362450 (+) for 7 days. Two hours following the final dosing, mice were euthanized and livers removed for RNA analysis. SHP and CYP8B1 expression was quantified by real-time PCR and normalized for GAPDH expression. Expression levels in C57BL/6J wild-type mice females were defined as 1.0. Values are the mean ± SEM (n = 6–7 animals per group). * P < 0.01 for regulation by WAY-362450. B: Male C57BL/6J wild-type (gray bars) or FXR^−/− mice (black bars) treated as in A were euthanized and a portion of the liver, the gall bladder, and the complete small intestine were removed. The contents of the taurine conjugates TCA, TCDCA, and TβMCA in these tissues were determined by LC/MS/MS and are reported as nmoles of conjugated bile acid per gram of body weight. Values are the mean ± SEM (n = 3 animals per group). * P < 0.05 for regulation by WAY-362450.