REGULATION OF FED INTESTINAL MOTILITY BY FAT

脂肪对进食肠道蠕动的调节

• 批准号: 2668309
• 负责人: HENRY C. LIN
• 金额: $ 11.9万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-03-15 至 2001-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2668309
• 关键词: biological signal transduction; chemoreceptors; cholecystokinin; chylomicrons; dietary lipid; dogs; gastrointestinal hormones; gastrointestinal motility /pressure; gastrointestinal nutrient absorption; hormone regulation /control mechanism; neural information processing; neuroendocrine system; neuropeptides; nutrition related tag

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.

脂肪的最佳消化和吸收取决于调节的呈现 这种营养素的吸收部位的小肠。 脂肪以负荷依赖性方式抑制肠道转运， 提供这种受控的营养输送， 脂肪仅限于近端肠道（空肠制动）或延伸到 远端肠（回肠制动）。为了让小肠做出反应 适当的脂肪进入，脂肪的存在，在管腔必须 被发现。传入神经，专门响应 在固有层中已经发现腔脂肪（脂肪化学感受器）。 由于这些神经的末端不与神经元接触， 与管腔接触的肠内分泌细胞可以充当肠内分泌细胞。 “味蕾”的小肠和行动的传入途径， 释放肽产物。我们的初步数据显示，PYY， 一种抑制肠道转运的肽，是吸收前信号 转换器和乳糜微粒（或其载脂蛋白组分，apo A-IV）是 吸收后信号转导器由于PYY细胞主要存在于 在远端肠道中，PYY可以通过近端肠道中的脂肪通过 神经依赖性，CCK刺激释放机制（空肠制动），但 远端肠道的脂肪可以通过神经独立的非神经依赖的方式释放PYY。 CCK刺激机制（回肠制动）。在项目的第一阶段，我们 将检查脂肪负荷的影响，脂肪暴露区域（近端 vs.远端肠道）和假设的介质对肠道运输和 释放PYY。在第二期工程中，我们会进一步研究 回肠PYY短期培养释放PYY的条件 细胞这一建议将提供基本的生理以及 机械信息来解释肠道传输的控制， 腔脂肪需要这些信息来开发新的，基于营养的 对因快速运输而出现症状的患者的治疗，包括 倾倒综合征，短肠综合征，迷走神经切断术后腹泻， 肠内喂养相关腹泻、胃切除术或回肠-肛门吻合术。