LIPID DETERMINANTS OF HIGH DENSITY LIPOPROTEIN (HDL) SUBFRACTION METABOLISM

高密度脂蛋白 (HDL) 亚组分代谢的脂质决定因素

• 批准号: 6338877
• 负责人: JOHN S PARKS
• 金额: $ 19.92万
• 依托单位: WAKE FOREST UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6338877
• 关键词: Cercopithecidae; apolipoproteins; atherosclerosis; blood lipoprotein metabolism; cardiovascular disorder prevention; chemical binding; circular dichroism; conformation; dietary lipid; disease /disorder model; enzyme linked immunosorbent assay; high density lipoproteins; immunoaffinity chromatography; lipid structure; liver metabolism; nuclear magnetic resonance spectroscopy; nutrition related tag; protein structure; unsaturated fatty acids

High density lipoprotein (HDL) concentrations are significantly lower in the plasma of human and non-human primates consuming diets enriched in polyunsaturated fatty acids(PUFA) compared to saturated or mono- unsaturated fat. The decrease in concentration appears to occur in apoA-I only HDL particles (LpA-I) with little change in LpA-I/A-II (particles containing both apoA-I and A-II). The goal of this project is to elucidate the basic mechanisms by which dietary fat saturation affects HDL production and catabolism. Our preliminary studies have shown that there is unidirectional conversion of small LpA-I (2 A-I per HDL) to medium (3 A-I per HDL) and large LpA-I (4 A-I per HDL) in vivo in African green monkeys, and that animals with low HDL have one fourth the conversion rate of small to large LpA-I compared to those with high HDL concentrations. We hypothesize that diet rich in PUFA compared to those containing saturated and mono-unsaturated fat lead to decreased production of small LpA-I and/or to decreased conversion of the small LpA-I to medium and large LpA- I. Alternatively, PUFA-rich diets may result in a faster catabolism of LpA-I from plasma. The decreased production of small LpA-I in animals led PUFA diets may result from decreased stability of apoA-I on HDL particles that contain PUFA, leading to poor assembly of apoA-I with lipid and hypercatabolism of lipid-free or lipid-poor apoA-I. In specific aim 1, in vivo catabolism studies with plasma LPA-I will be performed in African green monkeys to test the hypothesis that PUFA diets compared to saturated or mono-unsaturated fat lead to decreased LpA-I by the decreased production of small LpA-I and/or the decreased conversion of small LpA-I derived from African green monkeys will be performed to test the hypothesis that PUFA diets result in decreased conversion of nascent discoidal LpA-I secreted by the liver to spherical LpA-I. In specific aim 3, studies will be performed to test they hypothesis that PUFA diets result in a reduction of nascent LpA-I particles due to decreased intracellular and/or extracellular assembly of apoA-I with phospholipid. The basic information from this study will lead to a better understanding of HDL metabolism and could b tested to make more rational decisions concerning dietary treatment of individuals at risk for CHD.

高密度脂蛋白 (HDL) 浓度显着降低 食用富含以下物质的饮食的人类和非人类灵长类动物的血浆 多不饱和脂肪酸（PUFA）与饱和或单不饱和脂肪酸相比 不饱和脂肪。浓度下降似乎发生在 apoA-I 中 仅 HDL 颗粒 (LpA-I)，LpA-I/A-II 变化很小（颗粒 含有 apoA-I 和 A-II)。该项目的目标是阐明 膳食脂肪饱和度影响 HDL 的基本机制 生产和分解代谢。我们的初步研究表明，有 是小型 LpA-I（每个 HDL 2 个 A-I）到中等 LpA-I（3 非洲绿体内的大 LpA-I（每 HDL 4 个 A-I）和大 LpA-I（每 HDL 4 个 A-I） 猴子，高密度脂蛋白含量低的动物的转化率只有猴子的四分之一 与高 HDL 浓度的 LpA-I 相比，LpA-I 从小到大的变化。我们 假设富含 PUFA 的饮食与含有饱和脂肪酸的饮食相比 和单不饱和脂肪会导致小 LpA-I 的产生减少 和/或减少小LpA-I向中和大LpA-的转化 I. 另外，富含 PUFA 的饮食可能会导致更快的分解代谢 来自血浆的 LpA-I。动物中小 LpA-I 产量的减少导致 PUFA 饮食可能是由于 HDL 颗粒上 apoA-I 的稳定性降低所致 含有 PUFA，导致 apoA-I 与脂质组装不良， 无脂或缺脂 apoA-I 的过度分解代谢。在具体目标 1 中， 血浆 LPA-I 的体内分解代谢研究将在非洲进行 绿猴测试多不饱和脂肪酸饮食与饱和饮食相比的假设 或单不饱和脂肪导致 LpA-I 减少 小 LpA-I 的产生和/或小 LpA-I 的转化率降低 来自非洲绿猴的基因将被用来测试 假设多不饱和脂肪酸饮食会导致新生婴儿的转化减少 肝脏分泌的盘状LpA-I变成球形LpA-I。在特定目标下 3、将进行研究来检验他们的假设：PUFA饮食 由于减少，导致新生 LpA-I 颗粒减少 apoA-I 与磷脂在细胞内和/或细胞外组装。 本研究的基本信息将有助于更好地理解 HDL 代谢的影响，可以进行测试以做出更理性的决定 关于有冠心病风险的个体的饮食治疗。