Apo A2, C1 and C2 and Diet in human apoB Metabolism

载脂蛋白A2、C1和C2是极低密度脂蛋白（VLDL）、中密度脂蛋白（IDL）和低密度脂蛋白（LDL）的组成部分，称为载脂蛋白b （apoB）脂蛋白。动物模型和细胞研究表明，apoA2、C1和C2作为脂解和血浆载脂蛋白清除的调节剂具有重要作用。ApoA2和apo1具有损害VLDL的脂溶或肝脏和其他组织受体对其从血浆中摄取和清除的特性，或两者兼而有之。与对载脂蛋白e和C3（载脂蛋白的其他成分）的大量知识相比，对apoA2、C1和C2如何影响人体载脂蛋白代谢的知识几乎一无所知。我们建议使用稳定同位素内源性标记的示踪方法来揭示apoA2、C1和C2在载脂蛋白上的代谢途径。正常和轻度高甘油三酯血症患者的饮食由提供健康的20%脂肪或37%，主要是不饱和脂肪的食物组成。每种饮食3周后，通过静脉输注氘化氨基酸来追踪载脂蛋白代谢，受试者处于禁食状态，并在频繁小餐摄入期间再次进行追踪，以建立餐后稳定状态。将利用免疫亲和层析和超离心，从已经收集的样品中制备脂蛋白。该研究将确定载脂蛋白中apoA2、C1和C2在多大程度上影响高甘油三酯血症状态的建立，控制普通饮食的餐后反应，介导低脂与适度不饱和脂肪摄入对载脂蛋白浓度的影响，这是冠心病的既定危险因素。

Apolipoproteins A2, C1, and C2, are constituents of very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), and low density lipoproteins (LDL), termed "apoB lipoproteins". Animal models and cell studies suggest substantial roles for apoA2, C1 and C2 as modulators of lipolysis and clearance of apoB lipoproteins from plasma. ApoA2 and apoC1 have properties that impair either lipolysis of VLDL or its uptake and clearance from plasma by receptors on the liver and other tissues, or both processes. In contrast to the substantial body of knowledge about apoE and C3, other components of apoB lipoproteins, virtually nothing is known about how apoA2, C1 and C2 affect the metabolism of apoB lipoproteins in humans. We propose to use tracer methodology using endogenous labeling with stable isotopes to uncover the metabolic pathways related to apoA2, C1 and C2 on apoB lipoproteins. Normal and mildly hypertriglyceridemic persons were given diets composed of foods that provided healthy 20 percent fat or 37 percent, mainly unsaturated fat diets. After 3 weeks on each diet, their apoB lipoprotein metabolism was traced by intravenous infusion of deuterated amino acids, with the subjects in the fasting state and again during intake of frequent small meals to establish a postprandial steady state. Lipoproteins will be prepared, using immunoaffinity chromatography and ultracentrifugation, from samples already collected. The proposed study will determine to what extent apoA2, C1 and C2 in apoB lipoproteins influence the establishment of the hypertriglyceridemic state, control the postprandial response to common diets, and mediate the effects of low-fat vs moderate unsaturated fat intake on apoB lipoprotein concentrations, established risk factors for coronary heart disease.