EFFECT OF DIETARY LIPIDS ON THE FUNCTION OF CHYLOMICRONS

虽然许多饮食研究已经证明，慢性饮食的膳食脂肪组成改变空腹血浆脂蛋白胆固醇（CH）水平和发展动脉粥样硬化的风险，负责这些变化的具体机制还没有很好地建立。 膳食脂肪和CH是餐后（PP）乳糜微粒的唯一前体，但它们不参与空腹血中内源性脂蛋白的形成。 该建议的工作假设是，膳食脂肪组成通过影响PP乳糜微粒通过卵磷脂胆固醇酰基转移酶（LCAT）和/或胆固醇酯转移蛋白（CETP）催化的反应接受来自内源性脂蛋白和细胞膜的CH分子的能力，以及通过影响CH-CH清除率，改变空腹血浆中内源性脂蛋白CH水平和发生动脉粥样硬化的风险。从循环血液中富集乳糜微粒残留物。 为了验证这一假设，本研究将检查改变膳食脂肪组成对1）血浆脂蛋白CH和TG的水平、组成和密度谱，2）体内和体外LCAT和CETP介导的CH从内源性脂蛋白和/或细胞膜转移到富含PP TG的脂蛋白的程度，3）促进体内胆固醇逆向转运（RCT）的血浆内代谢活动和4）在PP脂血症的晚期清除阶段，乳糜微粒及其残留物在血液中的蓄积程度。 研究受试者（n=32）将从血脂正常的成年男性中招募，并将通过三种实验饮食（饱和脂肪、多不饱和脂肪和单不饱和脂肪）轮换，每种饮食持续20天。 在每个饮食干预期间将进行三项口服脂肪负荷研究。 每名受试者将作为自己的对照。 确定膳食脂肪组成对PP乳糜微粒从内源性脂蛋白和细胞膜接受CH并将其CH输送至肝脏排泄的效力的慢性和急性影响的研究应提供有关膳食脂肪组成改变动脉粥样硬化发展的机制的额外信息。

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.