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。 它的正常运输从 乳糜微粒的肠道与其生理分布有关 到外围的目标 非乳糜微粒转运的膳食脂质 很可能直接进入肝脏 脂质从 肝脏是极低密度脂蛋白，其代谢终产物是低密度脂蛋白， 胆固醇转运蛋白 本提案旨在研究机制 由此可以通过乳糜微粒从肠转运脂质， 调节和从肠到达肝脏的脂质量 记录在案。 将探索五个领域。 (1)由于磷脂酰胆碱 (PC)合成是提供磷脂表面的主要重要因素 乳糜微粒上的涂层，部分周转率和池大小， 将研究促进乳糜微粒形成的肠粘膜。 将研究PC合成的两种途径， 每一个都可以单独调节。 研究将在以下条件下进行 条件，其中进入淋巴的TG输出增加了因子 两个是生理学上的。 (2)将进行类似的研究， 确定粘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 乳糜微粒表面涂层的组分。 缺乏载脂蛋白B 与没有乳糜微粒形成相关，因此其充分的合成是 对乳糜微粒的正常运输至关重要 (3)将进行研究， 记录不通过淋巴转运的脂质的转运。 由于50%的输注脂质不在淋巴中转运，因此这些脂质交替 途径对于了解肠道脂质的定量重要 运输 这在粘膜细胞内发生的机制， 它的运输路线，大概是门静脉， 研究了 (4)吸收脂质的细胞内分布是 重要的是了解它的运输。 将进行研究， 将能够在细胞内识别粘膜乳糜微粒 前体池 更多的研究将集中在是什么导致了 脂质在低离心力下沉淀。 (5)新药能够 至少在肝脏中完全抑制PC合成。 因为相同的 生化途径存在于肠道中，这些药物将被研究 观察其对小肠PC合成的影响， TG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.