There is increasing interest in the effects of dietary lipids on plasma lipid and lipoproteins and possible effects on the development of atherosclerosis. The intestine has become recognized as making a major contribution to systemic lipoprotein metabolism. As a reflection of the large quantities of lipid which traverse the intestinal mucosa contributes important constituents (apoproteins phospholipids) to plasma lipoproteins. The effects of different dietary lipids on the intestinal synthesis and secretion of lipoproteins is therefore of interest and is the major focus of this grant. The proposed studies will quantitate chylomicron apoprotein synthesis and intracellular lipoprotein composition during varying conditions of lipid feeding and correlate these findings with lipoprotein composition and secretion rates in mesenteric lymph. The studies will be conducted using the mesenteric lymph fistula rat. The effects of saturated and unsaturated lipids, acute and chronic cholesterol feeding on intestinal apoprotein content and synthesis will be determined using recently developed radioimmunoassays for specific apoproteins as well as immunoprecipitation techniques to study apoprotein synthesis. Intracellular lipoproteins will be prepared from enterocytes and characterized to determine whether alterations are induced by a chronic lipid feeding. These findings will be correlated with apoprotein and lipoprotein composition and secretion rates in rat mesenteric lymph. In addition, apoprotein content and synthesis will be determined on human per oral intestinal biopsies after various lipid feedings. In a final series of studies, possible effects of altered lymph lipoprotein composition produced by dietary manipulations on the metabolic fate and clearance of these particles will be studied by infusion into donor rats. These studies should provide information concerning factors which modulate the intestinal contribution to lipoprotein metabolism.
