EFFECT OF FISH OIL ON LIPOPROTEIN METABOLISM

这些研究的总体目标是了解食用鱼类是如何 油调节血浆脂蛋白浓度。这类信息将 关注动脉粥样硬化与冠心病的重大问题 疾病。已知食用鱼油可降低血浆低密度脂蛋白和极低密度脂蛋白水平 在人类和包括老鼠在内的几个动物物种中。第一批 将进行研究，以量化和比较鱼类的影响 油、多不饱和蔬菜甘油三酯和饱和蔬菜 甘油三酯对低密度脂蛋白合成和分解代谢的影响。低密度脂蛋白比率 受体依赖和非受体依赖的低密度脂蛋白的合成及其速率 运输将在喂食不同量这三种物质的动物身上进行测量。 甘油三酯存在或不存在不同数量的 胆固醇。还将进行研究，以检验这些措施的影响 三种甘油三酯对极低密度脂蛋白合成和分解代谢的影响。第二 将进行一组研究，以阐明 鱼油调节低密度脂蛋白和极低密度脂蛋白的合成或分解代谢。研究 将首先确定鱼油是否会改变总胆固醇 保持肝脏和全身的平衡。总量的主要决定因素 身体的类固醇平衡是胆固醇吸收，即从头开始的胆固醇 胆汁中胆固醇的合成和分泌 在转化为胆汁酸之后。相应地，这三条路径将 在喂食鱼油、多不饱和蔬菜的动物体内定量 甘油三酯和饱和甘油三酯。其中每一项的影响 饮食调控对脂蛋白和膜脂肪酸组成的影响 将对血脂进行监测。根据这些研究的结果， 将进行实验，试图确定其作用机制 在分子水平上食用鱼油。由于鱼油中含有 相当数量的胆固醇和饱和脂肪酸，在一些 研究表明，将从鱼油中分离出相对纯净的omega-3脂肪酸 制备高效液相色谱检测及其药效及作用机制研究 如上所述检查的酸。最后，中国的某些降血脂药物 与鱼油结合可能会对血浆产生相加作用 脂蛋白水平和这种可能性将被探索。加在一起， 这些研究的结果将提供一个更好的理解 鱼油如何调节完整动物的胆固醇平衡和低密度脂蛋白代谢 动物。

The overall objective of these studies is to understand how dietary fish oil regulates plasma lipoprotein concentrations. Such information would bear on the important problem of atherosclerosis and coronary heart disease. Dietary fish oil is known to lower plasma LDL and VLDL levels in humans and in several animal species including the rat. The first group of studies will be undertaken to quantitate and compare the effect of fish oil, polyunsaturated vegetable triglyceride and saturated vegetable triglyceride on the synthesis and catabolism of LDL. Rates of LDL synthesis and rates of receptor-dependent and receptor-independent LDL transport will be measured in animals fed varying amounts of these three triglycerides in the presence or absence of varying amounts of cholesterol. Studies will also be done to examine the effect of these three triglycerides on the synthesis and catabolism of VLDL. The second group of studies will be undertaken to elucidate the mechanism by which fish oil regulates the synthesis or catabolism of LDL and VLDL. Studies will first be done to determine if fish oil alters gross cholesterol balance across the liver and whole body. The main determinants of total body sterol balance are cholesterol absorption, de novo cholesterol synthesis and the secretion of cholesterol into bile either as such or after conversion into bile acids. Accordingly, these three pathways will be quantitated in vivo in animals fed fish oil, polyunsaturated vegetable triglyceride and saturated triglyceride. The effect of each of these dietary manipulations on the fatty acid profile of lipoprotein and membrane lipids will be monitored. Depending on the outcome of these studies, experiments will be undertaken to try to define the mechanism of action of dietary fish oil at the molecular level. Since fish oil contains considerable amounts of cholesterol and saturated fatty acids, in some studies, relatively pure omega-3 fatty acids will be isolated from fish oil by preparative HPLC and the efficacy and mechanism of action of these fatty acids examined as described above. Finally, certain hypolipidemic drugs in combination with fish oil may produce additive effects on plasma lipoprotein levels and this possibility will be explored. Taken together, the results of these studies will provide a much better understanding of how fish oil regulates cholesterol balance and LDL metabolism in the intact animal.