REGULATION OF INTESTINAL LIPID TRANSPORT

描述：三酰甘油(TG)从肠腔的运动 乳杆菌微粒对淋巴的一个重要作用 肠粘膜细胞对乳糜粒的新陈代谢产生 乳杆菌残留物，高密度脂蛋白是作为产品生产的。新证据表明 这种残留物的产生导致了大多数高密度脂蛋白颗粒在 血浆。由于高密度脂蛋白是反向的胆固醇运输颗粒， 这项提案的主题，旨在理解 吸收的甘油三酯导向乳胶粒形成的机制 而不是通过门静脉直接进入肝脏，在临床上 很重要。 甘油三酯在内质网合成部位的运动 (呃)到高尔基山脉一直是一个重要但未被探索的研究领域 甘油三酯如何转运肠道细胞。PI的细胞生物学研究近况 实验室为一种独特的囊泡运输提供了大量证据 实现这一点的机制。Tg在内质网和内质网之间的移动速度 高尔基体与肠道将甘油三酯输送到 淋巴就像乳糜粒。初步数据显示，载脂蛋白AI是 存在于内质网，但不存在于运输小泡中。这导致建议 用实验来定义载脂蛋白AI与 内质网中发育中的乳糜粒及载脂蛋白AI在内质网沉积中的作用 ER中的环美康对Tg的影响。这些蛋白质负责 乳胶粒靶向TG转运过程中的肠道高尔基体 囊泡是一种胞质蛋白，负责融合 TG-运输囊泡与高尔基体结合，以及高尔基体上的对接蛋白 使肠道高尔基体具有所需的结合特异性， 将会被确定。研究还将确定 囊泡，并将确定TG和apoB-48从内质网到内质网的流动 TG-将囊泡运输到高尔基体。 调查人员发现，静脉注射阿司匹林 乳杆菌微粒子增加淋巴瘘患者淋巴中甘油三酯的输出 老鼠。应用程序的第二个目标是检查这是否是由于 乳胶粒残渣中磷脂酰胆碱的利用 TG-运输囊泡膜或乳胶粒表面形成。新开 合成的PC也将被研究，因为它优先用于 TG转运泡泡膜或乳胶粒表面与内质网的比较 膜PC。要确定是PC还是apo-B48驱动TG传输 在此过程中，还将进行胆瘘、甘油三酯注射和 TG+PC输注大鼠，以确定淋巴TG输出是否可以从 淋巴载脂蛋白B-48输出。

DESCRIPTION: The movement of triacylglycerol (TG) from the intestinal lumen to the lymph in a chylomicron particle is an important function of the intestinal mucosal cell since on metabolism of the chylomicron to produce a chylomicron remnant, HDL is produced as a product. New evidence suggests that remnant production results in the majority of the HDL particles in the plasma. Since HDL is the reverse cholesterol transport particle, the subject of this proposal, which is directed toward understanding the mechanisms by which absorbed TG is directed toward chylomicron formation rather than going directly to the liver via the portal vein, is clinically important. The movement of TG from its site of synthesis in the endoplasmic reticulum (ER) to the Golgi has been an important but unexplored area of research in how TG transits the enterocyte. Recent cell biological studies in the PI's laboratory provide considerable evidence for a unique vesicular transport mechanism for this. The rapidity of movement of TG between the ER and the Golgi correlates with the ability of the intestine to transport TG into the lymph as chylomicrons. Preliminary data show that apolipoprotein AI is present in the ER but not in the transport vesicle. This leads to proposed experiments to define the mechanism by which apoAI does not associate with the developing chylomicron in the ER, and the role of apoAI in the accretion of TG by the cylomicron in the ER. The proteins responsible for the targeting of chylomicrons to the intestinal Golgi in the TG-transport vesicle, the cytosolic protein responsible for enabling fusion of the TG-transport vesicle with the Golgi, and the docking protein on the Golgi that functions to give intestinal Golgi the required binding specificity, will be determined. Studies will also determine the composition of the vesicles, and will determine the flow of TG and apoB-48 from ER to TG-transport vesicle to Golgi. The investigator has found that the intravenous administration of chylomicrons increases the output of TG into the lymph in lymph fistula rats. The second aim of the application is to examine if this is due to the utilization of phosphatidylcholine (PC) from chylomicron remnants for either TG-transport vesicle membrane or chylomicron surface formation. Newly synthesized PC will also be studied for its preferential utilization for TG-transport vesicle membrane or chylomicron surfaces as compared to ER membrane PC. To determine whether PC or apo-B48 drives the TG transport process, studies will also be done in bile fistula, TG-infused and TG+PC-infused rats, to determine if lymph TG output can be dissociated from lymph apoB-48 output.