REGULATION OF HIGH DENSITY LIPOPROTEIN METABOLISM BY CHOLESTEROL AND JOJOBA OILS

高密度脂蛋白(HDL)被认为是抗动脉粥样硬化的， 因为它们能将多余的胆固醇从外周细胞中排出并转运 它以胆固醇酯的形式通过循环系统到达肝脏 它被降级了。这一反向胆固醇转运过程在 调节细胞内和血浆中的胆固醇浓度， 从而导致动脉粥样硬化的发生发展。当兔子被喂食的时候 胆固醇和/或饮食荷荷巴油，高密度脂蛋白(高密度脂蛋白胆固醇) 胆固醇喂养的兔子体内浓度降低，血浆中 霍霍巴油喂兔，并不改变胆固醇+霍霍巴油- 喂兔子。这项研究项目的长期目标是 为这两个相反的行为提供生化解释 饮食因素。由于载脂蛋白A-I(apoA-I)和总胆固醇 (游离胆固醇+胆固醇酯)是高密度脂蛋白的主要成分 颗粒，它们将被用作胆固醇和霍霍巴油如何 调节这些颗粒中的一种蛋白质和一种脂肪的水平。 这项研究项目的具体目标是量化 高密度脂蛋白中的载脂蛋白A-I和血清总胆固醇浓度 组分，以及来自新的高密度脂蛋白组分的HDL2和HDL3亚类 新西兰白兔。这些动物将被喂以正常饮食或 补充1%胆固醇或2%霍霍巴油或1%胆固醇+2%的 霍霍巴油21天，预定时间采血 在整个实验过程中。载脂蛋白A-I与总胆固醇浓度 将用酶联免疫吸附试验(ELISA)和 分别用酶法检测胆固醇。这些测量结果将 识别载脂蛋白A-I和总胆固醇的脂蛋白 浓度正在变化，并将测量速度、幅度和 这些变化的顺序。这项研究还将确定 大鼠小肠粘膜细胞apoA-I合成的相对速率 这些动物。兔载脂蛋白A-I的单特异性抗血清将用于 定量免疫沉淀法从标记小肠中提取载脂蛋白A-I 以确定饮食中的胆固醇和饮食中的 霍霍巴油调节这个器官中apoA-I的合成速度。这个 这些目标的实现将提供有关 膳食因素调节载脂蛋白A-I和总载脂蛋白的生化机制 兔血液中的胆固醇浓度，从而提供 更好地了解饮食因素如何调节高密度脂蛋白 这种动物的新陈代谢以及它在人类中的可能调节。

High density lipoproteins (HDL) are believed to be anti-atherogenic, because they remove excess cholesterol from peripheral cells and transport it through the circulatory system as cholesteryl esters to the liver where it is degraded. This reverse cholesterol transport process is important in regulating intracellular and plasma cholesterol concentrations and, thereby, the development of atherosclerosis. When rabbits are fed dietary cholesterol and/or dietary jojoba oil, HDL cholesterol (HDL-C) concentrations decrease in the cholesterol-fed rabbits, increase in the jojoba oil-fed rabbits, and do not change in the cholesterol + jojoba oil- fed rabbits. The long-term objective of this research project is to provide a biochemical explanation for the opposing actions of these two dietary factors. Since apolipoprotein A-I (apoA-I) and total cholesterol (free cholesterol + cholesteryl ester) are major components in HDL particles, they will be used as models of how cholesterol and jojoba oil regulate the levels of a protein and a lipid present in these particles. The specific aims of the research project are to quantitate the changes in apoA-I and total cholesterol concentrations in the serum, in the HDL fraction, and in the HDL2 and HDL3 subclasses of the HDL fraction from New Zealand White rabbits. These animals will be fed either a normal diet or one supplemented with 1% cholesterol or 2% jojoba oil or 1% cholesterol+2% jojoba oil for 21 days, and blood will be collected at predetermined times throughout the experiment. ApoA-I and total cholesterol concentrations will be quantified with an enzyme-linked immunosorbent assay (ELISA) and an enzymatic cholesterol assay, respectively. These measurements will identify those lipoproteins whose apoA-I and total cholesterol concentrations are changing and will measure the rate, the magnitude, and the sequence of these changes. This research will also determine the relative rates of apoA-I synthesis in small intestine mucosal cells from these animals. A monospecific antisera for rabbit apoA-I will be used to quantitatively immunoprecipitate apoA-I from labeled small intestine mucosal cells in order to determine if dietary cholesterol and dietary jojoba oil regulate the rate of apoA-I synthesis in this organ. The fulfillment of these objectives will provide useful information about the biochemical mechanism by which dietary factors regulate apoA-I and total cholesterol concentrations in the blood of the rabbit and, thereby, provide a better biochemical understanding of how dietary factors regulate HDL metabolism in this animal as well as its possible regulation in humans.