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）浓度的浓度显着降低 富含饮食的人类和非人类灵长类动物的血浆丰富 与饱和或饱和或单一的脂肪酸（PUFA）多不饱和脂肪酸（PUFA） 不饱和脂肪。浓度下降似乎发生在Apoa-I中 只有HDL颗粒（LPA-I），LPA-I/A-II几乎没有变化（颗粒 同时包含apoa-i和a-ii）。该项目的目的是阐明 饮食脂肪饱和影响HDL的基本机制 生产和分解代谢。我们的初步研究表明 是小lpa-i（每HDL 2 a-i）向培养基的单向转换（3 在非洲绿色 猴子，HDL低的动物具有转化率的四分之一 与HDL浓度高的LPA-I相比，LPA-I的小到大。我们 假设与含有饱和的饮食相比 单一不饱和脂肪会导致小LPA-I产生降低 和/或降低小LPA-I为中和大的LPA- I.另外，富含PUFA的饮食可能会导致更快的分解代谢 LPA-I来自等离子体。小动物LED的小lpa-i产生的生产减少 PUFA饮食可能是由于HDL颗粒上ApoA-I的稳定性降低而引起的 其中包含PUFA，导致apoa-i的脂质和脂质和 无脂质或脂肪贫乏的apoa-i的过量代谢。在特定目标1中 血浆LPA-I的体内分解代谢研究将在非洲进行 绿猴要测试PUFA饮食与饱和的假设 或单一不饱和脂肪导致LPA-I的减少。 小LPA-I和/或小LPA-I的转化率降低 将源自非洲绿猴子来测试 假设PUFA饮食导致新生的转化率降低 肝脏分泌的盘状LPA-I为球形LPA-I。在特定目标中 3，将进行研究以测试他们的假设是PUFA饮食 导致新生LPA-I颗粒的减少 ApoA-I与磷脂的细胞内和/或细胞外组装。 这项研究的基本信息将导致更好的理解 HDL代谢，可以进行B测试以做出更合理的决定 关于有冠心病风险的个体的饮食治疗。