LDL METABOLISM

目前，有几种啮齿动物的详细数据 不同器官胆固醇合成的调控机制 以及与血浆低密度脂蛋白相关的转运机制 用同样的纸巾清除。这样的量化数据有所改善 第一次提供了基础，为理解 实际调节循环血浆低密度脂蛋白-胆固醇水平的过程 并为探索这些影响的本质提供了手段 不同饮食、运动和药物对血脂水平的影响。 不幸的是，目前还没有这样的量化数据 灵长类物种。我们的研究将在活体条件下测量 食蟹鱼所有主要器官的胆固醇合成率 低、高膳食胆固醇摄入量条件下的猕猴 “有反应”和“无反应”的动物。此外，使用新的 开发的稳态输液技术，两者的绝对率 受体依赖型和非受体依赖型低密度脂蛋白 在这些相同的器官中，运输将被量化。《规则》 胆固醇合成和低密度脂蛋白转运的速度都将被研究。 在其他研究中，在以下情况下 饮食(长链的胆固醇含量或饱和度 脂肪酸)或在遗传背景上存在差异的情况下 动物们。后一组研究将特别重要 (相对于人类低密度脂蛋白生理学)自从成群的这些猴子 被定义为通过以下方式对增加的饮食胆固醇做出不利反应的 显著提高他们循环中的血浆胆固醇水平。这些 研究应该提供第一批体内定量数据 胆固醇合成和低密度的调节机制 这种灵长类动物主要器官中的脂蛋白运输，以及 这些数据应该为初步的数学计算提供手段 灵长类动物低密度脂蛋白周转的模拟。如果这些初步研究是 如果成功，它将为该物种的更广泛使用开辟道路 在灵长类动物体内低密度脂蛋白代谢的研究中。

Currently, there are detailed data available in several rodent species on the mechanisms of regulation of cholesterol synthesis in different organs and the transport mechanisms responsible for plasma low density lipoprotein clearance by these same tissues. Such quantitative data have improved have provided the basis, for the first time, for understanding the nature of the processes that actually regulate circulating plasma LDL-cholesterol levels and have provided the means for exploring the nature of the effects of different diets, exercise and pharmacologic agents on plasma lipid levels. Unfortunately, no such quantitative data are currently available in any primate species. Our studies will measure under in vivo conditions the rates of cholesterol synthesis in all of the major organs of the Cynomolgus monkey under circumstances of low and high dietary cholestrol intake in both "responding" and "nonresponding" animals. Furthermore, using a newly developed steady-state infusion technique, absolute rates of both receptor-dependent and receptor-independent low density lipoprotein transport will be quantitated in each of these same organs. Regulations of both rates of cholesterol synthesis and LDL transport will be investigated in other studies under circumstances where there has been an alteration in the diet (cholesterol content or degree of saturation of the long-chain fatty acids) or where there is a difference in the genetic background of the animals. This latter group of studies will be particularly important (relative to human LDL physiology) since groups of these monkeys have been defined which respond adversely to increased dietary cholesterol by markedly elevating their circulating plasma cholesterol levels. These studies should provide the first quantitative in vivo data on the mechanisms of regulation of cholesterol synthesis and low density lipoprotein transport in the major organs of this primate species, and these data should provide the means for the preliminary mathematical modeling of LDL turnover in the primate. If these preliminary studies are successful, it will open the way for the more extensive use of this species in the study of LDL metabolism in the primate.