CHOLESTEROL-RICH DIET AND PLASMA LIPID TRANSPORT

富含胆固醇的饮食和血浆脂质运输

• 批准号: 3358778
• 负责人: WOLFGANG P PATSCH
• 金额: $ 16.09万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-07-01 至 1992-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3358778
• 关键词: apolipoproteins; atherosclerosis; blood chemistry; blood lipoprotein; cholesterol analog; cholesterol esters; chylomicrons; dietary lipid; human subject; lipid transport; lipolysis; lipoprotein lipase; liver metabolism; nutrition related tag; phosphatidylcholine sterol acyltransferase; steroid biosynthesis; urinalysis

Epidemiologic data, clinical trials, and studies in laboratory animals have established a relationship between diets rich in saturated fat and cholesterol, atherogenic lipoproteins, and development of atherosclerosis. As a consequence of this information, diets low in cholesterol and saturated fat have been recommended. Adherence to low cholesterol diets imposes severe restrictions on the intake of eggs with major nutritional and economic implications. However, blanket recommendations for the U.S. population with regard to egg consumption may be challenged because of heterogeneity in the genetic makeup influencing an individual's response to dietary cholesterol. The goals of this proposal are i) to define the principal mechanism(s) which determine the reaction of the lipid metabolism to dietary cholesterol, and ii) to develop meaningful tests to identify hypo- and hyperresponders to excess dietary cholesterol. Our central hypothesis is that cholesterol homeostasis is intimately linked to the catabolism of chylomicrons in that ineffective clearance of chylomicrons fails to inhibit endogenous cholesterol synthesis and hepatic lipoprotein production and leads to accumulation of atherogenic lipoproteins in the circulation and, ultimately, to atherosclerosis. To test this hypothesis, hypo- and hyperresponders to excess dietary cholesterol will be identified by screening of normolipemic adults. In these subjects, adaptive responses of the plasma lipid transport system subsequent to 4 diets differing in cholesterol content (300 mg vs. 1700 mg/day) and P/S ratio (0.4 vs. 2.5) will be studied under strict metabolic and dietary control. Major fasting lipoprotein classes will be characterized and quantified, and activities of lipoprotein and hepatic lipase, LCAT, and cholesteryl ester transfer protein will be measured at the end of each dietary period. Catabolism of alimentary and endogenous lipoproteins will be assessed by measuring the concentration of TG in plasma, and of retinyl ester and apoB-48/apoB-100 in the d less than 1.019 lipoproteins in the course of lipemia after a standardized oral fat load. Clearance of dietary fat will be related to inhibition of endogenous cholesterol synthesis as determined by plasma mevalonate levels and HMG- CoA reductase activity in mononuclear blood cells. Postprandial lipoproteins will be characterized physicochemically, and their interaction with macrophages will be determined as an index of atherogenicity. The relationship of chylomicron catabolism to hepatic lipoprotein production will be studied in the cholesterol fed rabbit. These studies should enhance our understanding of how lipid metabolism is affected by dietary cholesterol.

流行病学数据、临床试验和实验室研究 动物们已经建立了一种关系，即富含 饱和脂肪和胆固醇，致动脉粥样硬化的脂蛋白，以及 动脉粥样硬化的发展。其结果就是 信息，低胆固醇和饱和脂肪的饮食一直是 推荐的。坚持低胆固醇饮食会强制实施严重的 限制摄入含有主要营养和营养成分的鸡蛋 对经济的影响。然而，全面的建议是 在鸡蛋消费方面，美国人口可能是 由于基因构成的异质性而受到挑战 影响个体对饮食中胆固醇的反应。这个 本提案的目标是：一)明确主体机制(S) 它们决定了脂肪代谢对饮食的反应 胆固醇，以及ii)开发有意义的测试来识别低胆固醇- 以及对过量饮食胆固醇的高反应者。我们的中央 假设胆固醇动态平衡与 乳糜体在无效清除中的分解代谢 乳胶粒不能抑制内源性胆固醇合成和 肝脂蛋白生成并导致肝脂蛋白蓄积 循环中的致动脉粥样硬化脂蛋白，并最终导致 动脉硬化。为了检验这一假说，我们先来看看 对过量饮食胆固醇的高反应者将通过以下方式确定 血脂正常的成年人的筛查。在这些受试者中，适应性 4小时后血浆脂质转运系统的反应 胆固醇含量不同的饮食(300毫克对1700毫克/天) P/S比值(0.4vs.2.5)将在严格的代谢条件下进行研究 和饮食控制。主要的空腹脂蛋白类别将是 脂蛋白和脂蛋白的性质和活性。 肝脂酶、LCAT和胆固醇酯转移蛋白 在每个饮食周期结束时测量。人体的分解代谢 食物和内源性脂蛋白将通过以下方式进行评估 测定血浆中甘油三酯和视黄酸酯的浓度 和载脂蛋白B-48/apoB-100中的脂蛋白少于1.019个。 标准化口腔脂肪负荷后的脂血症病程。净空 膳食脂肪将与内源性胆固醇的抑制有关 甲氧丙戊酸血药浓度和HMG- 单个核血细胞中辅酶A还原酶活性。餐后 脂蛋白的物理化学特征，以及它们的 与巨噬细胞的相互作用将被确定为 致动脉粥样硬化。乳糜管分解代谢与肿瘤的关系 肝脂蛋白的产生将在胆固醇中进行研究 喂兔子。这些研究应该会增进我们对 饮食中胆固醇是如何影响脂肪代谢的。