Dissociation between cholesterol secretion and plasma lipid transfer activity in rabbits

Human and rabbit plasma contains a lipid transfer protein that transfers cholesteryl esters and triglycerides among the plasma lipoproteins and may also have a role in the movement of lipids into and out of cells. Little is known about the regulation of the activity of the lipid transfer protein, but in the rabbit, hypercholesterolemia is associated with increased plasma lipid transfer activity (LTA). Perfused rabbit livers secrete LTA, and hepatic cholesterol secretion is increased in rabbits with diet-induced hypercholesterolemia. Thus, experiments were performed with rabbits to determine if LTA is regulated by a concerted hepatic secretion of lipoprotein protein cholesterol and LTA. Rabbits were fed chow or chow plus coconut oil (14% wt/wt), and plasma lipids, LTA, and the rate of secretion of cholesterol into plasma were determined. Coconut oil feeding increased plasma cholesterol by 68%, LTA by 42%, and hepatic cholesterol secretion by 69%. Mevinolin (75 mg/day), an inhibitor of cholesterol biosynthesis, lowered LTA and plasma cholesterol without affecting the rate of secretion of cholesterol into plasma. These studies provide further evidence that, in the rabbit, plasma cholesterol and LTA are closely related, and the association is not likely to be caused by a concerted hepatic secretion of cholesterol and LTA.