DIETARY LIPIDS--EFFECTS ON LIPID-LIPOPROTEIN METABOLISM

我们提出了一系列综合的临床和生化研究。 为了更好地描述特定膳食脂类对血脂和 受试者的脂蛋白代谢。饮食对人类健康的影响 单不饱和脂肪酸代表的主要脂肪来源将是 比较它们与同类产品的降脂效果 饮食中含有30%的热量来自omega-6多不饱和脂肪酸 或者主要是饱和脂肪酸，这两种脂肪酸都与低脂 节食。所有的饮食都将喂给患有原发性高胆固醇血症的受试者 有待研究的脂蛋白代谢参数包括 血、尿~(125)I-低密度脂蛋白转换率、胆固醇稳态的研究 新鲜分离的人甲伐他酸排泄与胆固醇合成 单核白细胞。这四种饮食将被喂给服用 无胆固醇饮食和每天600毫克的饮食 胆固醇。长链多不饱和脂肪的代谢效应 从鱼油中提取的酸将在项目概述的研究中进行检验 2.这些研究的目的是检查是否有降甘油三酯的作用 长链omega-3多不饱和脂肪酸主要是由于 二十碳五烯酸或二十二碳六烯酸 纯化的脂肪酸(作为饮食成分)可防止碳水化合物诱导 高甘油三酯血症。高密度脂蛋白降低的机制 喂食低胆固醇鱼的高胆固醇血症受试者的血药浓度 油将通过用125I标记的高密度脂蛋白进行动力学研究来检测。 鱼油对前列腺素形成的影响将在 合作研究。这些研究应该会增进我们的知识 关于长链omega-3脂肪的抗动脉粥样硬化作用 酸。甾醇对血脂和脂蛋白的影响 将检测正常和高胆固醇血症受试者的血药浓度。 饲料中添加海鲜类固醇。最后，第四个项目 旨在检查三个阶段的降胆固醇效果 在志愿者中谨慎饮食，建立食谱开发 实验室，并前瞻性地评估饮食的有效性 咨询作为长期控制血脂的辅助手段 门诊部。总体而言，这些研究应该会增进我们的知识 关于特定膳食脂肪的临床和代谢影响 并可直接应用于治疗 高胆固醇血症。

We propose an integrated series of clinical and biochemical investigations to better delineate the effects of specific dietary lipids on lipid and lipoprotein metabolism in human subjects. The influence of diets in which monounsaturated fatty acids represent the main source of fat will be investigated in terms of their lipid lowering effects compared to similar diets containing 30% of calories from omega-6 polyunsaturated fatty acids or primarily saturated fatty acids and both of these compared to a low fat diet. All diets will be fed to subjects with primary hypercholesterolemia and parameters of lipoprotein metabolism to be studied will include 125I-LDL turnover, cholesterol homeostasis assessed by serum and urinary excretion of mevalonic acid and cholesterol synthesis in freshly isolated mononuclear leukocytes. These four diets will be fed to subjects consuming a cholesterol-free diet and in the presence of 600 mg/day of dietary cholesterol. The metabolic effects of long chain polyunsaturated fatty acids derived from fish oil will be examined in studies outlined in Project 2. These studies aim to examine whether the hypotriglyceridemic effects of long-chain omega-3 polyunsaturated fatty acids are due primarily to eicosapentaenoic acid or docosahexaenoic acid by determining if these purified fatty acids (as dietary constituents) prevent carbohydrate induced hypertriglyceridemia. The mechanisms responsible for the reduction of HDL concentrations in hypercholesterolemic subjects fed a low cholesterol fish oil will be examined by performing kinetic studies with 125I-labeled HDL. The influence of fish oils on prostanoid formation will be examined in collaborative studies. These studies should further our knowledge concerning the anti-atherosclerotic effects of long chain omega-3 fatty acids. The influence of sterols on plasma lipid and lipoprotein concentrations will be examined in normal and hypercholesterolemic subjects fed diets supplemented with seafood sterols. Finally, the fourth project aims to examine the hypocholesterolemic effects of three phases of a prudent diet in volunteer subjects, establish a recipe development laboratory, and prospectively assess the effectiveness of dietary counseling as an adjunct to long-term control of plasma lipids in an outpatient setting. Overall, these studies should enhance our knowledge concerning the clinical and metabolic effects of specific dietary lipids and have direct therapeutic application to treatment of subjects with hypercholesterolemia.