REGULATION OF INTESTINAL LIPID TRANSPORT

肠道脂质运输的调节

• 批准号: 6176424
• 负责人: CHARLES Milton MANSBACH
• 金额: $ 22.01万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-05-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6176424
• 关键词: Golgi apparatus; acyl group; apolipoprotein B; apolipoproteins; blood lipoprotein metabolism; chylomicrons; endoplasmic reticulum; fatty acid transport; gastrointestinal absorption /transport; glycerol; high density lipoproteins; intracellular membranes; intracellular transport; laboratory rat; lipid metabolism; lipid transport; lymph; nutrition related tag; phosphatidylcholines; protein binding; triglycerides; vesicle /vacuole

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.

描述：三酰甘油（TG）从肠腔中的运动 在乳糜微粒中的淋巴是一个重要的功能， 肠粘膜细胞，因为对代谢的乳糜微粒，以产生一个 乳糜微粒残余物，HDL作为产物产生。 新的证据表明 残余物的产生导致了大部分HDL颗粒在 等离子体 由于HDL是胆固醇的反向转运颗粒， 这一建议的主题，这是为了了解 吸收的TG直接形成乳糜微粒的机制 而不是通过门静脉直接进入肝脏， 重要. TG从其在内质网中的合成位点的移动 (ER)一直是一个重要但尚未探索的研究领域， TG是如何通过肠上皮细胞的 PI的近期细胞生物学研究 实验室提供了大量证据，证明了一种独特囊泡运输 机制对此。 TG在ER和ER之间移动的速度 高尔基体与肠道将TG转运到胃肠道的能力相关。 乳糜微粒。 初步数据显示，载脂蛋白AI是 存在于ER中，但不存在于运输囊泡中。 这导致了建议 实验来定义apoAI不与 内质网中乳糜微粒的发育以及apoAI在内质网增生中的作用 在急诊室里用环微球检测TG 蛋白质负责 TG转运中乳糜微粒对肠高尔基体的靶向 囊泡，负责使融合的细胞质蛋白质， TG-转运囊泡与高尔基体，以及高尔基体上的对接蛋白 其功能是给予肠高尔基体所需的结合特异性， 将被确定。 研究还将确定 囊泡，并将决定TG和apoB-48从ER到 TG-运输囊泡到高尔基体。 研究人员发现，静脉内给予 乳糜微粒增加了淋巴瘘中TG向淋巴的输出 大鼠 申请的第二个目的是审查这是否是由于 利用乳糜微粒残留物中的磷脂酰胆碱（PC） TG转运囊泡膜或乳糜微粒表面形成。 新 合成PC也将研究其优先利用， 与ER相比，TG转运囊泡膜或乳糜微粒表面 膜PC。 为了确定是PC还是apo-B48驱动TG运输， 在这一过程中，还将对胆瘘、TG输注和 TG+ PC输注大鼠，以确定淋巴TG输出是否可以与 淋巴apoB-48输出。