The original goals of the clinical investigator aware were to isolate and characterize intracellular and secreted lipoproteins of the intestine. This application has 2 specific objectives - to characterize apoprotein and lipid interactions leading to the formation of a lipoprotein and to characterize the metabolic fate of secreted intestinal lipoproteins. Insights into intestinal lipoprotein metabolism should provide a basis for dietary modifications of circulating lipoproteins, as the intestine is a major contributor to systemic apoprotein and lipid levels. The long-term goal of these studies is the reduction of atherosclerosis through modifications in lipoprotein metabolism. The proposed studies on intracellular lipoprotein assembly concern the process of formation of intracellular lipoproteins prior to secretion. 3H-leucine or 3H-lipid will be administered intraduodenally to rats and intestinal epithelial cells harvested following experiments in which the time and route of exposure of the radiolabel is varied. The specific activity of newly synthesized apoprotein, triglyceride and cholesteryl ester will be determined by immunoprecipitation and radioimmunoassay in each lipoprotein fraction. By studying the pattern of specific activity variation, the process by which apoproteins and lipid combine to form lipoproteins will be characterized. The portal vein and mesenteric lymph will be examined as secretory routes for intestinal LDL and HDL following administration of 3H-cholesterol to label the cholesteryl ester core of newly synthesized intestinal lipoproteins. The catabolic fate of intestinal lipoproteins will be studied by incorporating 3H-cholesteryl-ether, a nondegradable analogue of cholesteryl ester, into intestinal HDL and then analyzing the tissue deposition sites for the 3H-ether.
