Figure 1. Insulin regulates cholesterol homeostasis in a FoxO1-dependent manner.

(A-K) Mice with hepatic deletion of the insulin receptor (Insulin Receptor Liver-Knockout or IR L-KO), FoxO1 (FoxO1 Liver-Knockout, or FoxO1 L-KO), or both (Insulin Receptor and FoxO1 Liver-Double Knockout, or IR/FoxO1 L-DKO) as well as their littermate controls (FLOX) were sacrificed at 8–10 weeks of age (n=5–30). Livers were subjected to real-time PCR analysis (A-D,H-K) or cholesterol measurement (E). (F) Cholesterol absorption was measured at 13 weeks of age as the percentage of an oral bolus of [¹⁴C]-cholesterol absorbed using the dual isotope method⁴¹. (G) Gallbladder bile was subjected to HPLC analysis, and the percentage of 12HBAs was calculated as described in methods. Error bars represent SEM; *p<0.05. A.U., arbitrary units.