EFFECT OF FISH OIL ON LIPOPROTEIN METABOLISM

这些研究的总体目标是了解饮食中的鱼类 油调节血浆脂蛋白浓度。 这种信息将 关系到动脉粥样硬化和冠心病的重要问题 疾病 众所周知，膳食鱼油可降低血浆LDL和VLDL水平， 人类和包括大鼠在内的几种动物物种中。 第一组 将进行研究，以量化和比较鱼类的影响， 油、多不饱和植物甘油三酯和饱和植物 甘油三酯对LDL合成和催化的影响。 LDL的比率 受体依赖性和受体非依赖性低密度脂蛋白的合成和速率 将在喂食不同量的这三种物质的动物中测量转运 甘油三酯在存在或不存在不同量的 胆固醇 还将进行研究，以检查这些措施的效果。 三种甘油三酯对VLDL合成和催化的影响。 第二 将进行一组研究，以阐明 鱼油调节LDL和VLDL的合成或分解。 研究 将首先确定鱼油是否会改变总胆固醇 肝脏和全身的平衡。 总体的主要决定因素 身体固醇平衡是胆固醇吸收，从头胆固醇 胆固醇的合成和分泌进入胆汁， 转化为胆汁酸后。 因此，这三条途径将 在喂食鱼油、多不饱和蔬菜 甘油三酯和饱和甘油三酯。 每一个的影响 脂蛋白和膜脂肪酸谱的饮食调控 将监测脂质。 根据这些研究的结果， 将进行实验，试图确定的作用机制， 食用鱼油在分子水平。 由于鱼油含有 大量的胆固醇和饱和脂肪酸， 研究表明，相对纯的omega-3脂肪酸将从鱼油中分离出来， 通过制备型HPLC和这些脂肪酸的功效和作用机制， 如上所述检查酸。 最后，某些降血脂药物， 与鱼油结合可能对血浆产生叠加效应 脂蛋白水平和这种可能性将进行探讨。 综合起来看， 这些研究的结果将提供一个更好的理解， 鱼油如何调节胆固醇平衡和LDL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.