Idiopathic Hypercholesterolemia: Demonstration of an Impaired Feedback Control of Cholesterol Synthesis in vivo

The influence of dietary cholesterol on the synthesis of cholesterol by the liver was studied in liver biopsy samples from human infants. Dietary cholesterol in amounts of 3 to 4g per day suppressed almost completely the synthesis of cholesterol by the liver. Acetate-C14 was orally administered to the infants fed normal or high-cholesterol diet, and the appearance of labeled lipids in the plasma was studied. The feeding of cholesterol depressed the incorporation of acetate-C14 into the plasma cholesterol fraction. In a patient with idiopathic hypercholesterolemia, the feeding of cholesterol had no inhibitory effect upon the incorporation of acetate-C14 into the plasma cholesterol fraction. The results of these studies indicate that infants do normally possess a feedback control of hepatic cholesterol synthesis and that this mechanism is impaired in an infant with idiopathic hypercholesterolemia.