Effect of intravenous infusion of Intralipid, cholesterol, and plant sterols on hepatic cholesterogenesis.

Male Wistar rats were infused intravenously with various amounts (2-20 mL/24 h) of Intralipid or Intralipid containing cholesterol or plant sterols (5-100 mg/24h), and hepatic cholesterogenesis was monitored by measuring the incorporation of [1-14C]acetate into the nonsaponifiable sterols of liver slices. It was observed that the infusion of Intralipid alone resulted in a hypercholesterolemia that varied with the amount of Intralipid administered and that it was accompanied by up to a threefold increase in hepatic cholesterogenesis. Inclusion of cholesterol in the Intralipid at 5 mg/mL prevented the increase in hepatic cholesterol biosynthesis, while an inhibition of up to 95% of control synthesis was achieved when a total of 33 mg of cholesterol in 20 mL Intralipid was infused over a 24-h period. It is concluded that the feedback regulation of cholesterol biosynthesis is operative even when the entry of cholesterol bypasses the intestine and the lipoprotein synthesis taking place there and that Intralipid is a suitable medium for the intravenous introduction of a large mass of metabolically active cholesterol molecules. Similar infusions of mixed plant sterols failed to prevent the activation or inhibition of cholesterol biosynthesis, but the administration of much larger doses of plant sterols (100 mg) brought about a partial inhibition of hepatic cholesterogenesis. It is concluded that the presence of an alkyl group in the side chain prevents the plant sterols from an effective interaction with the critical sites of the feedback regulatory system of cholesterogenesis. The effects of the larger doses of plant sterols were attributed to the displacement of increasing amounts of free cholesterol from the vascular tissues, which resulted in an effective elevation of plasma cholesterol levels. The infusion of either cholesterol or plant sterols over the 24-h period did not appear to have a consistent effect upon the composition or secretion of biliary bile acids.