The overall objectives of the proposal are to delineate factors within the intestinal epithelium which control the formation of triglyceride-rich lipoproteins and to determine how changes within the intestine may modify the intestinal contribution of important lipoprotein constituents to systemic lipoprotein metabolism. Specific radioimmunoassay procedures for the measurement of apoproteins (A-I, A-IV, B) within intestinal epithelium of rat and man will be developed. The mucosal content of these apoproteins will be determined under various dietary perturbations of lipid metabolism and correlated in rats with apoprotein/lipoprotein secretion into mesenteric lymph. Preliminary results have applied a RIA for apoA-I to rat intestine with the finding that crypt cells contain significant amounts of apoA-I as do ileal epithelial cells. Triglyceride absorption is associated with a marked increase in the content of epithelial cell apoA-I. Biliary diversion which increases cholesterol synthesis within the intestinal mucosa and depletes it of triglyceride is associated with no reduction in mucosal apoA-I levels. These findings suggest additional stimuli for apoA-I synthesis. Cholesterol feeding in rats is associated with the appearance of beta-VLDL in lymph and a decreased apoA-I content of lymph demonstrating that intestinal lipoprotein secretion may be altered by chronic cholesterol feeding. Future studies are planned to more clearly define factors influencing intestinal lipoprotein secretion.