REGULATION OF FED INTESTINAL MOTILITY BY FAT

脂肪的最佳消化和吸收取决于调节的呈现方式 将这种营养物质转移到小肠的吸收部位。 脂肪以一种负荷依赖的方式抑制肠道转运 提供这种受控的营养输送，无论接触的区域 脂肪仅限于近端肠道(空肠制动)或延伸至 远端肠道(回肠制动)。为了让小肠有反应 适当地将脂肪输入，管腔内脂肪的存在必须 被发现。一种传入神经，专为响应 腔脂肪(脂肪化学感受器)已在固有层中被发现。 由于这些神经的末端不与 管腔，与管腔接触的肠道内分泌细胞可以起到 “味蕾”的小肠和作用于传入通路通过 释放一种多肽产品。我们的初步数据显示，PYY，a 抑制肠道转运的多肽是前吸收信号 转导子和乳胶粒(或其载脂蛋白成分，载脂蛋白A-IV)是 后吸收信号换能器由于PYY细胞主要被发现 在远端肠道中，PYY可能通过近端肠道中的脂肪通过 神经依赖，CCK刺激的释放机制(空肠制动)，但 远端肠道中的脂肪可能通过一种神经独立的、非 CCK刺激机制(回肠制动)。在计划的第一阶段，我们 将检查脂肪负荷的影响，脂肪暴露的区域(近端 Vs.远端肠道)和假想的肠道转运介质和 PYY的发布。在第二期工程中，我们会进一步研究 短期培养回肠PYY的释放条件 细胞。这项提议将提供基本的生理学和 解释肠道转运控制的机制信息 流明脂肪。这些信息是开发新的、以营养为基础的 对因快速运输而出现症状的患者的治疗包括 有倾倒综合征，短肠综合征，迷走神经切断术后腹泻， 肠内喂养引起的腹泻、胃切除或回肠肛管吻合术。

Optimal digestion and absorption of fat depend on regulated presentation of this nutrient to the absorptive sites of the small intestine. Intestinal transit is inhibited by fat in a load-dependent fashion to provide this controlled nutrient delivery whether the region of exposure to fat is limited to the proximal gut (jejunal brake) or extended to the distal gut (ileal brake). In order for the small bowel to respond appropriately to the fat entered, the presence of fat in the lumen must be detected. Afferent nerves that fire specifically in response to luminal fat (fat chemoreceptors) have been found in the lamina propria. Since the terminal ends of these nerves are not in contact with the lumen, a gut endocrine cell in contact with the lumen may serve as a "taste bud" for the small intestine and act on the afferent pathways by releasing a peptide product. Our preliminary data showed that PYY, a peptide that inhibits intestinal transit, is the preabsorptive signal transducer and chylomicron (or its apoprotein component, apo A-IV) is the postabsorptive signal transducer. Since PYY cells are principally found in the distal gut, PYY may be released by fat in the proximal gut via a neurally dependent, CCK-stimulated release mechanism (jejunal brake) but fat in the distal gut may release PYY via a neurally independent, non CCK-stimulated mechanism (ileal brake). In Phase I of the project, we will examine the effect of fat load, the region of fat exposure (proximal vs. distal gut) and the hypothesized mediators on intestinal transit and the release of PYY. In Phase II of the project, we will further examine the conditions for PYY release in a short term culture of ileal PYY cells. This proposal will provide the fundamental physiologic as well as mechanistic information to explain the control of intestinal transit by luminal fat. Such information is needed to develop novel, nutrient-based treatments for patients who are symptomatic from rapid transit including those with dumping syndrome, short bowel syndrome, postvagotomy diarrhea, enteral feeding related diarrhea, gastrectomy, or ileo-anal anastomosis.