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CHOLESTEROL-RICH DIET AND PLASMA LIPID TRANSPORT

富含胆固醇的饮食和血浆脂质运输

基本信息

批准号：
3358780
负责人：
WOLFGANG P PATSCH
金额：
$ 16.93万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
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/3358780
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

项目摘要

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，饱和脂肪和胆固醇，致动脉粥样硬化脂蛋白，动脉粥样硬化的发展。由于这种信息，低胆固醇和饱和脂肪的饮食一直是推荐坚持低胆固醇饮食会严重影响限制鸡蛋的摄入量，经济影响。然而，对于美国人在鸡蛋消费方面可能由于基因组成的异质性，影响个体对饮食胆固醇的反应。的本建议的目标是：（一）确定主要机制; 它决定了脂质代谢对饮食的反应，胆固醇，和ii）开发有意义的测试，以确定低，以及对过量饮食胆固醇的过度反应。我们的中央假设胆固醇稳态与乳糜微粒在无效清除乳糜微粒不能抑制内源性胆固醇合成，肝脂蛋白的产生，并导致积累循环中致动脉粥样硬化的脂蛋白，最终，动脉粥样硬化为了验证这一假设，对过量膳食胆固醇的高反应者将通过以下方法来鉴定：正常血脂成人的筛查。在这些主题中，适应性血浆脂质转运系统的反应后，4 饮食中胆固醇含量不同（300 mg vs 1700 mg/天）和P/S比（0.4 vs. 2.5）将在严格的代谢条件下进行研究饮食控制。主要空腹脂蛋白类别将是表征和定量，以及脂蛋白和肝脂肪酶、LCAT和胆固醇酯转移蛋白将在每个饮食周期结束时测量。分解代谢营养和内源性脂蛋白将通过测量血浆中TG和视黄酯的浓度载脂蛋白B-48/载脂蛋白B-100在d中小于1.019脂蛋白在d中标准化口服脂肪负荷后的脂血症过程。清除膳食脂肪与内源性胆固醇的抑制有关合成，如通过血浆甲羟戊酸水平和HMG- 单核血细胞中CoA还原酶活性。餐后脂蛋白将被物理化学表征，并且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性乳糜微粒与胃溃疡的关系肝脂蛋白的产生将在胆固醇中进行研究。喂兔子这些研究应能增进我们对饮食中胆固醇如何影响脂质代谢。