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节机制 以及负责血浆低密度脂蛋白的转运机制 清除这些组织。 这些定量数据已经得到改善， 第一次为理解宇宙的本质提供了基础 实际上调节循环血浆LDL-胆固醇水平的过程 并提供了探索影响的性质的手段， 不同的饮食、运动和药物对血脂水平的影响。 不幸的是，目前没有任何此类定量数据。 灵长类动物 我们的研究将在体内条件下测量 食蟹猴所有主要器官中的胆固醇合成速率 在低和高膳食胆固醇摄入情况下， “有反应”和“无反应”的动物。 此外，使用新的 开发了稳态输注技术， 受体依赖性和受体非依赖性低密度脂蛋白 将对这些相同器官中的每一个中的转运进行定量。 条例 将研究胆固醇合成和低密度脂蛋白转运的速率 在其他研究中， 饮食（胆固醇含量或长链脂肪酸的饱和度） 脂肪酸）或在遗传背景存在差异的情况下， 那些动物 后一组研究将特别重要 （相对于人类低密度脂蛋白生理学），因为这些猴子的群体已经 定义为对增加的膳食胆固醇有不利反应， 显著提高了他们循环血浆胆固醇水平。 这些 研究应提供关于 调节胆固醇合成和低密度的机制 这种灵长类动物主要器官中的脂蛋白转运，以及 这些数据应该提供了初步的数学手段， 灵长类动物LDL转换的模型。 如果这些初步研究 如果成功，将为更广泛地利用这一物种开辟道路 研究灵长类动物的低密度脂蛋白代谢。

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.