Both HC and LC can effectively ameliorate hypercholesterolemia and regulate cholesterol homeostasis via the activation and inhibition of hepatic (AMPKα and PPARα) and intestinal (ACAT2) cholesterol-modulators, respectively, as well as the modulation of downstream signals (LDLR and CYP7A1). The gene discussed is PPARA; the disease is familial hypercholesterolemia.