EFFECT OF FISH OIL ON LIPOPROTEIN METABOLISM

鱼油对脂蛋白代谢的影响

• 批准号: 3354060
• 负责人: DAVID K SPADY
• 金额: $ 17.75万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-04-01 至 1994-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3354060
• 关键词: Macaca fascicularis; atherosclerosis; blood lipoprotein; blood lipoprotein metabolism; blood lipoprotein transport; cholesterol; chylomicrons; coronary disorder; dietary lipid; fatty acids; hamsters; high performance liquid chromatography; lipoprotein lipase; liver metabolism; low density lipoprotein; marine animal oil; membrane reconstitution /synthesis; messenger RNA; nutrition related tag; pathogenic diet; radiotracer; receptor binding; saturated fatty acids; triglycerides; unsaturated fats; very low density lipoprotein

The overall objective of these studies is to understand how dietary fatty acids regulate the concentration of LDL in plasma. The concentration of LDL in plasma is determined by at least four factors including 1) the rate of LDL production (J-t ) , 2) the maximal rate of receptor dependent LDL transport (J-max ), 3) the affinity if the LDL particle; for the LDL receptor (K-m) and 4) the rate of receptor independent LDL transport (P). Using new quantitative techniques to measure each of these processes in vivo, we have recently shown that the type of fatty acids in the diet can markedly affect both the! production and the receptor dependent catabolism of LDL by the liver. These effects will be studied in much greater detail in hamsters and Cynomolgus monkeys using diets designed to evaluate the effect of number and configuration of double bonds, saturated fatty acid chain length and level of dietary fat. One group of studies will then investigate the mechanism by which dietary fatty acids regulate the LDL receptor pathway. Since changes in cholesterol availability are known to regulate the LDL receptor pathway, fatty acid-induced changes in receptor dependent LDL transport will be correlated with changes in tissue and whole body cholesterol balance and with changes in', receptor protein and mRNA levels; changes in receptor dependent uptake will also be correlated with changes in the composition and physical properties of liver membranes. A second group of studies will be carried out to determine how dietary fatty acids regulate the rate of LDL production. Since LDL are formed during the metabolism of VLDL, studies will be done to determine how dietary fatty acids regulate the rate of VLDL synthesis by the liver, the activities of hepatic and lipoprotein lipase in metabolizing VLDL to LDL particles and VLDL remnants, and the rate at which VLDL remnants are cleared by the liver. A third group of studies will be undertaken to determine if dietary fatty acids affect chylomicron remnant transport and, if so, whether this could account for changes in receptor dependent LDL transport. A final group of studies will be undertaken to determine if diet-induced changes in the composition and physical properties of LDL affect the affinity of LDL for its receptor in vivo. Overall, these detailed and quantitative studies should provide basic information on how specific dietary fatty acids regulate plasma LDL concentrations (and thus the risk of coronary heart disease) both at the physiological and cell biological level.

这些研究的总体目标是了解膳食脂肪 酸调节血浆中LDL的浓度。 的浓度 血浆中的LDL由至少四个因素决定，包括：1） LDL生成速率（J-t），2）受体依赖性的最大速率 LDL转运（J-max），3）LDL颗粒的亲和力;对于LDL 受体非依赖性LDL转运率（P < 0. 05）。 使用新的定量技术来测量这些过程中的每一个， 体内，我们最近表明，饮食中的脂肪酸类型可以 两者都有明显的影响！生产和受体依赖 肝脏对LDL的催化作用。 这些影响将在很大程度上进行研究。 在仓鼠和食蟹猴中使用设计用于 评价双键的数目和构型的影响， 饱和脂肪酸链长度和膳食脂肪水平。 一组 研究将探讨膳食脂肪酸 调节LDL受体途径。 因为胆固醇的变化 已知可用性调节LDL受体途径，脂肪 酸诱导的受体依赖性LDL转运的变化将是 与组织和全身胆固醇平衡的变化相关， 受体蛋白和mRNA水平的变化;受体 依赖性摄取也将与组合物的变化相关 和肝膜的物理性质。第二组研究 将进行，以确定如何膳食脂肪酸调节 LDL生产率。 由于LDL是在代谢过程中形成的， VLDL，研究将确定膳食脂肪酸如何调节 肝脏合成VLDL的速率、肝脏和 脂蛋白脂酶代谢VLDL为LDL颗粒和VLDL 残余物，以及VLDL残余物被肝脏清除的速率。 第三组研究将确定饮食中的脂肪 酸影响乳糜微粒残留物的运输，如果是这样，这是否可以 解释受体依赖性LDL转运的变化。 最后一组 将进行研究，以确定饮食引起的变化， LDL的组成和物理性质影响LDL对 其受体在体内。 总的来说，这些详细的定量研究 应提供关于特定膳食脂肪酸 调节血浆LDL浓度（从而降低冠心病风险） 疾病）在生理和细胞生物学水平上。