Although numerous diet studies have demonstrated that dietary fat composition of chronic diets alters fasting plasma lipoprotein cholesterol (CH) levels and the risk of developing atherosclerosis, the specific mechanisms responsible for these alterations are not well established. Dietary fat and CH are the exclusive precursors of postprandial (PP) chylomicrons, but they do not enter into the formation of endogenous lipoproteins in fasting blood. The working hypothesis of this proposal is that dietary fat composition alters endogenous lipoprotein CH levels in fasting plasma and the risks of developing atherosclerosis by influencing the ability of PP chylomicrons to accept CH molecules from endogenous lipoproteins and cell membranes through the reactions catalyzed by lecithin cholesterol acyltransferase (LCAT) and/or cholesterylester transfer proteins (CETP) and by influencing the rate of the clearance of CH-enriched chylomicron remnants from circulating blood. To test this hypothesis, this study will examine the acute and chronic effect of altering dietary fat composition on 1) level, composition and density spectrums of plasma lipoprotein CH and TG, 2) the extent of LCAT and CETP-mediated transfer of CH from endogenous lipoproteins and/or cell membranes into PP TG-rich lipoproteins in vivo and in vitro, 3) intraplasma metabolic activities that promote the reverse cholesterol transport (RCT) in vivo and 4) the extent of accumulation of chylomicrons and their remnants in the blood at a late clearance stage of PP lipemia. Study subjects (n=32) will be recruited from a pool of normolipidemic adult males and will be rotated through three experimental diets (saturated fat, polyunsaturated fat, and monounsaturated fat), each diet lasting for 20 days. Three oral fat loading studies will be conducted during each dietary intervention period. Each subject will serve as his own control. The studies determining the chronic and acute effect of dietary fat composition on the potencies of PP chylomicrons to accept CH from endogenous lipoproteins and cell membranes and to deliver their CH to the liver for excretion should provide additional information about the mechanisms by which the dietary fat composition alters the development of atherosclerosis.
