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

人类 apoB 代谢中的 Apo A2、C1 和 C2 与饮食

• 批准号: 6546459
• 负责人: FRANK M SACKS
• 金额: $ 59.17万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6546459
• 关键词: apolipoprotein B; apolipoproteins; blood lipoprotein metabolism; cardiovascular disorder risk; dietary lipid; eating; enzyme linked immunosorbent assay; fasting; human middle age (35-64); human tissue; hypertriglyceridemia; immunoaffinity chromatography; lipolysis; nutrition related tag; pathologic process; patient oriented research; plasma; protein structure; protein structure function; stable isotope; ultracentrifugation; unsaturated fats; very low density lipoprotein

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.

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）的组分，称为“apoB脂蛋白”。 动物模型和细胞研究表明apoA2、C1和C2作为脂解和apoB脂蛋白从血浆中清除的调节剂具有重要作用。 ApoA2和apoC1具有损害VLDL的脂解或其通过肝脏和其他组织上的受体从血浆中的摄取和清除或这两个过程的特性。 与关于apoE和C3（apoB脂蛋白的其他组分）的大量知识相反，关于apoA2、C1和C2如何影响apoB脂蛋白在人体中的代谢几乎一无所知。 我们建议使用示踪方法，使用内源性标记稳定同位素，以揭示相关的代谢途径apoA2，C1和C2的载脂蛋白B脂蛋白。 正常人和轻度高脂血症者的饮食由提供健康的20%脂肪或37%脂肪的食物组成，主要是不饱和脂肪饮食。 每种饮食3周后，通过静脉输注氘代氨基酸追踪受试者的载脂蛋白B脂蛋白代谢，受试者处于空腹状态，并在频繁少量进食期间再次进行，以建立餐后稳态。 将使用免疫亲和色谱法和超离心法从已采集的样本中制备脂蛋白。 拟议的研究将确定apoB脂蛋白中的apoA2、C1和C2在多大程度上影响高脂血症状态的建立，控制对普通饮食的餐后反应，并介导低脂与中度不饱和脂肪摄入对apoB脂蛋白浓度的影响，这些脂蛋白浓度是冠心病的既定危险因素。