REGULATION OF INTESTINAL LIPID TRANSPORT

三酰甘油(TG)是最有效的热量来源 身体及其吸收不良是疾病的信号。它的正常传输是从 乳糜粒中的肠道与其生理分布有关 到外围的目标。非乳糜粒转运的膳食脂肪是 很可能会直接进入肝脏。脂类从血管内的转运 肝脏是极低密度脂蛋白，其代谢最终产物是主要血清低密度脂蛋白 胆固醇转运体。这项建议旨在研究机制。 由此，通过乳糜粒从肠道运输的脂肪可以 调节的和从肠道到达肝脏的脂肪的量 有记录在案。将探索五个领域。(1)自卵磷脂 (PC)合成在提供磷脂表面方面起着重要作用 乳糜管上的涂层，流失率和水池大小 我们将研究乳糜粒形成所需的肠粘膜。 我们将研究合成聚碳酸酯的两条路线，因为 每一项都可以单独监管。研究将在以下条件下进行 淋巴甘油三酯输出量增加1倍的条件 两个是通过生理手段。(2)将进行类似的研究，以 确定黏膜前体池的大小和部分周转率 载脂蛋白B48和A1。这些载脂蛋白是主要的蛋白质。 乳胶粒表面涂层的成分。载脂蛋白B的缺失是 与没有乳胶粒形成有关，因此其适当的合成 对正常的乳糜粒运输至关重要。(3)将进行研究，以 记录不通过淋巴运输的脂质的运输情况。 由于50%注入的脂肪不是在淋巴中运输的，所以这些交替 从数量上讲，途径对了解肠道脂质很重要 运输。这种情况发生在粘膜细胞内的机制和 它的运输路线，大概是门静脉，将是 调查过了。(4)吸收的脂质在细胞内的分布为 对于理解它的运输很重要。将进行以下研究 将能够在细胞内鉴定粘膜乳胶粒 前驱体库。其他研究将集中在哪些诱因被吸收上。 在低离心力下将脂肪转化为颗粒。(5)新药能够 至少在肝脏中完全抑制PC的合成。由于同样的原因 肠道中存在生化途径，这些药物将被研究 观察其对肠道PC合成的影响及对大鼠肠道PC合成的影响。 热重运输。

Triacylglycerol (TG) is the most efficient caloric source available to the body and its malabsorption signals disease. Its normal transport from the intestine in chylomicrons is associated with its physiological distribution to targets in the periphery. Non-chylomicron transported dietary lipid is likely to be delivered directly to the liver. Lipid transport from the liver is in VLDL whose metabolic end product is LDL, the major serum cholesterol transporter. This proposal is designed to study mechanisms whereby lipid transport from the intestine via chylomicrons can be modulated and the amount of lipid reaching the liver from the intestine documented. Five areas will be explored. (1) Since phosphatidylcholine (PC) synthesis is of major import in providing the phospholipid surface coat on chylomicrons, the fractional turnover rate and pool size in intestinal mucosa which subserves chylomicron formation will be studied. Both routes by which PC can be synthesized will be investigated because each may be separately regulated. The studies will be performed under conditions in which TG output into the lymph is increased by a factor of two by physiological means. (2) Similar studies will be performed to determine the mucosal precursor pool size and fractional turnover rate for apo-lipoproteins B48 and A1. These apo-lipoproteins are major protein components of the chylomicron surface coat. The absence of apo-B is associated with no chylomicron formation so that its adequate synthesis is crucial to normal chylomicron transport. (3) Studies will be performed to document the transport of lipid that is not transported via the lymph. Since 50% of infused lipid is not transported in the lymph, these alternate pathways are quantitatively important to understanding intestinal lipid transport. The mechanism by which this occurs within the mucosal cell and the route of its transport, presumedly the portal vein, will be investigated. (4) The intracellular distribution of absorbed lipid is important in understanding its transport. Studies will be performed which will enable the intracellular identification of the mucosal chylomicron precursor pool. Additional studies will focus on what induces absorped lipid to pellet under low centrifugal force. (5) New drugs are able to completely inhibit PC synthesis at least in liver. Since the same biochemical pathways are present in intestine, these drugs will be studied to observe their effect on PC synthesis in the intestine and its effect of TG transport.