Figure 5

The effect of FXR ligands on PPL expression. (A) Representative images for hepatic PPL distribution in Fxr ^+/+ and Fxr ^−/− mice fed the control or 1% CA-containing diet for 7 days. Scale bar: 100 μm. (B) Hepatic mRNA and protein expression of PPL in Fxr ^+/+ and Fxr ^−/− mice under normal and CA-fed conditions. Five mice per group were examined. The immunoblot for GAPDH was used as the loading control. (C) Hepatic PPL distribution in NMF-fed (lean) or HFD-fed (obese) mice following CA feeding. Scale bar: 100 μm. (D) Hepatic mRNA and protein expression of PPL in lean and obese mice following CA feeding. Four mice per group were examined. The immunoblot for GAPDH was used as the loading control. (E) Hepatic Ppl and Cyp7a1 mRNA expression levels in mice acutely administered CA or GW4064 via oral gavage at the indicated doses. Five mice per group were examined. The immunoblot for PPL is also shown. Equal amounts of protein from 5 mice were combined in each group for western blotting. The immunoblots for GAPDH were used as the loading controls. (F) Ppl and Shp mRNA expression levels in mouse primary hepatocytes administered FXR ligands at the indicated concentrations. Four samples per group were examined. (−), untreated; Veh, vehicle. mRNA expression levels are normalized to Gapdh. The average values in control diet-fed Fxr ^+/+ mice (B), lean mice (D), or vehicle-treated groups (E and F), were set to 1.0. Values represent mean ± SD. *, **, ***, ****: P < 0.05, 0.01, 0.001, and 0.0001, respectively, by one-way ANOVA with post hoc tests (Bonferroni’s test [B and D] or Dunnett’s test [F; vs. Veh]), Steel’s test (E [CA vs. Veh]), or unpaired t test (E [GW4064 vs. Veh]). ND, not determined.