Figure 8. Quetiapine increases intestinal lipid absorption in a PXR-dependent manner.

Eight-week-old male PXR^fl/fl and PXR^ΔIEC littermates were treated with vehicle control or 10 mg/kg/day of quetiapine by oral gavage for 1 week. (A and B) Distribution (A) and AUC (B) of radioactivity in intestinal segments of PXR^fl/fl and PXR^ΔIEC mice after an oral challenge of oil containing [³H]-cholesterol for 2 hours (n = 5, 2-way ANOVA, *P < 0.05, **P < 0.01). (C and D) Cholesterol (C) and triglyceride (D) absorption rates in control or quetiapine-treated PXR^fl/fl and PXR^ΔIEC mice. Mice were injected with lipase inhibitor poloxamer-407 followed by gavage with [³H]-cholesterol (C) or [³H]-triolein (D). Plasma samples were collected over 6 hours and measured for the presence of [³H]-cholesterol or [³H]-triolein (n = 3–7, 2-way ANOVA, *P < 0.05, and **P < 0.01 compared with PXR^fl/fl mice treated with control; †P < 0.05, compared with PXR^ΔIEC mice treated with quetiapine). (E and F) Mice received an intragastric lipid load (10 μl/g body weight of olive oil) after 4-hour fasting. Blood samples were collected 2 hours after the lipid bolus, and postprandial plasma triglyceride (E) and cholesterol (F) levels were measured by standard methods (n = 4–6, 2-way ANOVA, *P < 0.05).