KINETICS OF HUMAN POSTPRANDIAL LIPOPROTEIN METABOLISM

流行病学研究和实验室正在积累证据 支持这一假设的调查表明， 促进餐后脂蛋白代谢 动脉硬化。脂蛋白示踪研究的技术进展 现在使我们有可能在一个新的水平上研究 血浆脂蛋白是餐后在肠道和 肝脏。这项拟议研究的总体目标是揭示 餐后脂蛋白途径可能影响 动脉粥样硬化的发展，以研究这些途径在正常和 并测试饮食对高甘油三酯血症患者的影响。 操纵。 我们将确定肠道的基本代谢途径 和血浆中肝脂蛋白颗粒系统的示踪 载脂蛋白B48和B100；即颗粒的大小 产生的、脂解级联的程度、停留时间和 缓慢代谢的残留物的存在 可能会导致动脉粥样硬化。我们将研究是否存在 载脂蛋白E和C-III调节滞留时间、清除 肠道和肝脏极低密度脂蛋白和低密度脂蛋白的比率和相互转换 来源，或它们是否是致动脉粥样硬化残留颗粒的标志。 载脂蛋白E和C-III在高密度脂蛋白和极低密度脂蛋白/低密度脂蛋白之间转移的动力学 被量化。 特定目标1将比较餐后脂蛋白动力学 摄入具有空腹脂蛋白动力学特征的第1步饮食 高甘油三酯血症和正常血脂受试者。特定目标2将 研究替代碳水化合物或单不饱和脂肪的效果 针对饱和脂肪对餐后脂蛋白代谢的影响。全天的 肠道和肝脏脂蛋白的浓度模式 原产地以及示踪剂动力学将被研究。白天的 浓度研究和示踪动力学研究是相辅相成的，后者 描述了产生峰值的机制 餐后浓度。 这些研究将增加我们对代谢途径的了解 餐后被激活或抑制的，并可能导致 减少动脉粥样硬化发展的治疗方法。

Evidence is building from epidemiological studies and laboratory investigations to support the hypothesis that abnormalities in lipoprotein metabolism during the postprandial period promote atherosclerosis. Technological advances in lipoprotein tracer studies now make it possible to study at a new level of sophistication the plasma lipoproteins that are formed postprandially in the intestine and the liver. The overall goal of the proposed research is to uncover postprandial lipoprotein pathways that are likely to influence the development of atherosclerosis, to study these pathways in normal and hypertriglyceridemic persons, and to test the effect of dietary manipulation. We will determine the fundamental metabolic pathways of the intestinal and hepatic lipoprotein particle system in plasma as traced by apolipoprotein B48 and B100; that is, what sizes of particles are produced, the extent of a lipolytic cascade, the residence times, and the existence of slowly metabolized remnant particles that are potentially atherogenic. We will study whether the presence of apolipoproteins E and C-III modulates the residence times, clearance rates and interconversions of VLDL and IDL of intestinal and hepatic origin, or whether they are markers of atherogenic remnant particles. The kinetics of apo E and C-III transfer between HDL and VLDL/IDL will be quantified. Specific Aim 1 will compare postprandial lipoprotein kinetics during intake of a Step 1 diet with fasting lipoprotein kinetics in hypertriglyceridemic and normolipidemic subjects. Specific Aim 2 will study the effect of substituting carbohydrate or monounsaturated fat for saturated fat on postprandial lipoprotein metabolism. Diurnal concentration patterns of lipoproteins of intestinal and hepatic origin, as well as tracer kinetics will be studied. The diurnal concentration and tracer kinetic studies are complementary, the latter delineating the mechanisms responsible for producing the peak postprandial concentrations. These studies will increase our understanding of the metabolic pathways that are activated or suppressed postprandially, and could lead to treatments for reducing the development of atherosclerosis.