CYP3A4 and familial hypercholesterolemia: In the proof-of-concept experiments, we investigated the metabolic effects of MI-883 in humanized PXR-CAR-CYP3A4/3A7 mice fed either with a high-fat diet (HFD) to induce diet-induced metabolic syndrome with hypercholesterolemia or with a high-cholesterol diet (HCD) to induce diet-induced hypercholesterolemia (Fig. 4a, f).