EFFECT OF FISH OIL ON LIPOPROTEIN METABOLISM

这些研究的总体目标是了解饮食中的脂肪 酸调节血浆中低密度脂蛋白的浓度。浓缩物 血浆中的低密度脂蛋白由至少四个因素决定，包括1) 低密度脂蛋白产生速率(J-t)，2)受体依赖的最大速率 低密度脂蛋白转运(J-max)，3)低密度脂蛋白颗粒的亲和力；低密度脂蛋白 受体(K-m)和4)受体非依赖性低密度脂蛋白转运率(P)。 使用新的定量技术来测量这些过程中的每一个 体内，我们最近已经表明，饮食中的脂肪酸类型可以 明显地影响到！生产与受体依赖 肝脏分解低密度脂蛋白的代谢。这些影响将被深入研究。 在仓鼠和食蟹猴中使用设计为 评价双键数目和构型的影响， 饱和脂肪酸链长和膳食脂肪水平。一组 然后，研究将探讨膳食脂肪酸的机制 调节低密度脂蛋白受体途径。因为胆固醇的变化 已知的有效性是调节低密度脂蛋白受体途径，脂肪 酸诱导的受体依赖性低密度脂蛋白转运的变化将是 与组织和全身胆固醇平衡的变化有关 随着受体蛋白和mRNA水平的变化；受体的变化 依赖摄取也将与成分的变化相关。 以及肝膜的物理性质。第二组研究 将进行研究以确定膳食脂肪酸如何调节 低密度脂蛋白的生成率。因为低密度脂蛋白是在低密度脂蛋白代谢过程中形成的 极低密度脂蛋白，将进行研究以确定饮食脂肪酸如何调节 肝脏合成极低密度脂蛋白的速率、肝脏和肝脏的活动 脂蛋白脂酶将极低密度脂蛋白代谢为极低密度脂蛋白颗粒和极低密度脂蛋白 残留物以及极低密度脂蛋白残留物被肝脏清除的速度。 将进行第三组研究，以确定饮食中的脂肪 酸影响乳杆菌残留物的运输，如果是这样，这是否会 解释了受体依赖的低密度脂蛋白运输的变化。最后一组 将进行一系列研究，以确定饮食是否会导致 低密度脂蛋白的组成和物理性质影响低密度脂蛋白对蛋白质的亲和力 它在体内的受体。总体而言，这些详细和定量的研究 应提供有关特定膳食脂肪酸如何 调节血浆低密度脂蛋白浓度(从而降低冠心病风险 疾病)在生理和细胞生物学水平上。

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.