HEPATIC METABOLISM OF DIET DERIVED LIPOPROTEINS

在此期间，该项目的总体目标是 从分子水平上理解饮食中的胆固醇是如何 由肝脏代谢的。为此，有三个具体目标 建议：1)进一步表征残留物的清除 路径。具体地说，似乎有两种低密度脂蛋白 受体依赖和非依赖通路。我们将使用 抗低密度脂蛋白受体抗体，以消除其对 过程，然后了解残留新陈代谢是如何在 缺乏低密度脂蛋白受体。我们将尝试将 通过电子显微镜处理并纯化相关结合 从生化角度来看。肝脂酶在清除肝脏中的作用 将对过程进行研究。2)研究低密度脂蛋白的后果 受体依赖和低密度脂蛋白受体非依赖残留物 清除对肝脂代谢的影响。具体来说，我们将 测定非低密度脂蛋白受体介导的受体的数量和作用 并试图解释残留物运移较慢的原因 残留物的降解率高于β-极低密度脂蛋白。3)至 非胆固醇对肝脏低密度脂蛋白调节作用的研究 在肝脏中的受体，并评估这对 残留代谢。具体来说，我们将研究 胰岛素和尚未确定的肝脏的作用机制 特异性生长因子刺激低密度脂蛋白受体。我们将进行 进一步研究肿瘤引起的肿瘤减少的机制 低密度脂蛋白受体。这些研究所达成的理解可能 最终帮助设计的养生法导致 预防动脉粥样硬化和胆石症。

The overall goal of the project during this period has been to understand, at a molecular level, how cholesterol from the diet is metabolized by the liver. To this end, three specific aims are proposed: 1) To further characterize the remnant removal pathway. Specifically, it appears that there are both LDL receptor-dependent and -independent pathways. We will use an antibody to the LDL receptor to eliminate its contribution to the process and then learn how remnant metabolism proceeds in the absence of the LDL receptor. We will attempt to visualize the process by electron microscopy and to purify the relevant binding site biochemically. The role of hepatic lipase in the removal process will be studied. 2) To study the consequences of LDL receptor-dependent and LDL receptor-independent remnant removal on hepatic lipid metabolism. Specifically, we will determine the amount and effects of non-LDL receptor-mediated remnant transport and attempt to explain the basis for the slower rate of degradation of remnants than beta-VLDL. 3) To characterize non-cholesterol mediated regulation of hepatic LDL receptors in liver and evaluate the consequence of this on remnant metabolism. Specifically, we will examine the mechanism whereby insulin and an as yet unidentified liver specific growth factor stimulate LDL receptors. We will conduct further studies of mechanisms of neoplasia-induced decrease in LDL receptors. The understanding achieved by these studies may eventually aid in the design of regimens that lead to the prevention of atherosclerosis and cholelithiasis.