The proposed research is designed to investigate the metabolic pathways through which apoproteins present in chylomicrons and very low density lipoproteins are transferred to other lipoprotein classes or catabolized by the liver. Hypercholesterolemic rats will be used as models. Hypercholesterolemia will be produced by feeding diets containing cholesterol and cholic acid. More severe hypercholesterolemia will be prduced by feeding this diet to rats made diabetic with streptozotocin. Plasma from these rats contains particles ranging in size from that of chylomicrons to chylomicron remnants (1500-4900A). These particles have a high content of cholesteryl esters and also contain A-1, which is not usually found in the d less than 1.006 lipoproteins of the rat. The metabolism of these cholesterol-rich particles will be studied and compared to that of triglyceride-rich chylomicrons and remnants produced from them. This investigation will utilize in vivo turnover experiments and studies of receptor-mediated uptake of abnormal lipoproteins by the perfused rat liver.
