Secretion of Lipoprotein Cholesterol by Perfused Livers from Rabbits Hypo- or Hyperresponsive to Dietary Cholesterol: Greater Dietary Cholesterol-Induced Secretion in Hyperresponsive Rabbits

In two inbred strains of rabbits with high or low response of plasma cholesterol to dietary cholesterol, secretion of lipoprotein cholesterol by perfused livers was determined. The perfused rabbit livers secreted cholesterol into the perfusate at essentially constant rates between 30 and 120 min of perfusion. Most of the secreted cholesterol resided in VLDL. Addition of cholesterol to the diet of the donor rabbits caused a higher cholesterol:triglyceride ratio of lipoproteins secreted by the perfused liver. Such a rise was also seen in the plasma lipoproteins of cholesterol-fed rabbits. Plasma and perfusate lipoproteins differed in that the former had a higher cholesterol:triglyceride ratio. Cholesterol feeding produced a higher output of lipoprotein cholesterol by the perfused liver, the increment being greater in hyper- than in hyporesponders. Cholesterol-fed hyperresponders had higher liver cholesterol concentrations than their hyporesponsive counterparts. There was a direct relationship between the rise of liver cholesterol concentrations and the rise of hepatic secretion of lipoprotein cholesterol; this relationship was identical for hypo- and hyperresponders. We conclude that the higher cholesterolemic response to cholesterol feeding in the hyperresponders, when compared with the hyporesponders, can be explained, at least partly, by a greater cholesterol-induced hepatic secretion of lipoprotein cholesterol.