Hyperresponsiveness to dietary cholesterol in inbred rabbits is not associated with enhanced reduction in binding of beta-VLDL to liver membranes

In two inbred strains of rabbits with high or low response of serum cholesterol to dietary cholesterol, binding of rabbit beta-VLDL to hepatic membrane preparations was determined. The objective was to test the hypothesis that after cholesterol feeding, hyperresponders show a more dramatic reduction in hepatic apolipoprotein (apo) B/E receptors, which may explain the development of the high degree of cholesterolemia in these animals. The number of hepatic high affinity receptors for beta-VLDL in hyperresponders fed a diet without added cholesterol was, on average, 20% lower than that in hyporesponders. After the addition of increasing amounts of cholesterol to the diet, liver cholesterol concentrations were elevated to a greater extent in hyper- than in hyporesponsive rabbits. Liver free cholesterol concentrations were negatively associated with maximal binding of beta-VLDL to liver membranes. With increasing liver free cholesterol concentrations, maximal binding was less effectively depressed in hyper- than hyporesponders. We conclude that in the inbred strains of rabbits, hyperresponsiveness to dietary cholesterol is not caused by enhanced depression of hepatic apo B/E receptors.