THE ROLE OF THE CEPHALIC PHASE OF FEEDING IN THE REGULATION OF GASTROINTESTIN

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 摘要 在禁食状态下，胃会分泌一种新的胃肠肽Ghrelin，并受到食物摄入量的抑制。当给人类服用时，它被发现增加了卡路里的摄入量。在动物研究中，它增加了食物的摄入量、体重和脂肪沉积。 相比之下，胃肠肽YY3-36(PYY3-36)最近被认为是一种饮食调节的饱腹感信号。它在餐后立即从胃肠道释放，并抑制食欲素信号神经肽Y的释放。尽管Ghrelin和PYY显然都是热量摄入和食欲的重要调节因素，但调节它们合成和分泌的因素尚不清楚。当一个人咀嚼食物但不吞下食物时，以及在服用M受体阻滞剂后，血浆中的Ghrelin水平会因假喂食而降低。这些发现表明，Ghrelin的分泌，以及其他调节食欲的胃肠激素的潜在分泌，可能受到与食物的思想、气味或味道有关的神经和/或其他激素因素的控制。这项研究的目的是确定这些神经感觉输入是否可以调节这些胃肠激素的释放，这些神经感觉输入共同构成了进食的“头部阶段”。 为了验证我们的假设，我们将在禁食期间测量10名瘦身受试者和10名肥胖但其他方面健康的受试者的血清Ghrelin、PYY 3-36和其他与食欲有关的“肠道”激素水平，并在每隔20分钟测量一次，每次持续140分钟，进行以下干预：在房间里安静休息时；观察和闻一闻标准餐；观察、闻、尝和咀嚼标准餐，但不摄入；以及观察、闻、尝、嚼和吞食标准餐。 假设 1.假喂食试验引起瘦肉型个体胃促生长素水平的变化。 2.这些变化也出现在肥胖者身上。 具体目标 1.测定10名瘦(BMI 18-25)健康成人空腹及下列各项情况下的血清Ghrelin、PYY 3-36及其他与食欲有关的“胃肠”激素水平： A.安静地在房间里休息； 观察和闻一顿标准的食物； 观察、闻和品尝标准的食物，但不能吞食； 观察、闻、尝和摄取标准的食物。 2.对10名肥胖(BMI 30-35)的健康人重复同样的程序。 背景和意义 Ghrelin是一种新的胃肠肽，被认为可以增加食欲。在禁食状态下，胃会分泌胃促生长素，在进食或交感神经活动增强的状态下，如甲亢时，胃促生长激素会受到抑制。当给人类服用时，它被发现增加了卡路里的摄入量。在动物研究中，它可以增加食物的摄入量、体重和脂肪沉积。因此，Ghrelin似乎起到了膳食调节的食欲信号的作用。 相比之下，胃肠肽YY3-36(PYY3-36)最近被认为是饮食调节的厌食症或饱腹感信号。这种多肽是Y2R受体的激动剂。它在餐后立即从胃肠道释放，并集中作用于下丘脑的弓状核，以抑制促食欲素信号的释放，神经肽Y.PYY已被证明在给药时降低食欲和食物摄入量。 虽然Ghrelin和PYY显然都是食物大小、卡路里摄入量、食欲和饱腹感的重要调节者，但调节它们合成和分泌的因素仍不清楚。上胃肠道中食物的存在很可能只是几个因素中的一个，这些因素可能以相互的方式调节它们的分泌。Arosio等人最近的一项初步实验的结果。研究表明，当一个人咀嚼食物但不吞下食物时，以及服用毒扁豆碱阻滞剂后，血浆中的Ghrelin水平会因假喂食而降低。这些具有挑衅性的发现表明，Ghrelin的分泌，以及潜在的其他调节食欲的胃肠激素的分泌，可能受到与食物的思想、气味或味道有关的神经和/或其他激素因素的控制。这项研究的目的是确定这些神经感觉输入是否可以调节Ghrelin和PYY的释放，这些神经感觉输入共同构成了进食的“头部阶段”。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. ABSTRACT In the fasting state the stomach secretes Ghrelin, a novel gastrointestinal peptide, and it is suppressed by food intake. When administered to humans, it was found to increase caloric intake. In animal studies, it increases food intake, body weight and fat deposition. In contrast, the gastrointestinal peptide YY 3-36 (PYY 3-36) recently has been proposed to be a meal-regulated satiety signal. It is released from the gastrointestinal tract in the immediate postprandial state, and inhibits the release of the orexigenic signal neuropeptide Y. Although both ghrelin and PYY are clearly important regulators of caloric intake and appetite, the factors that regulate their synthesis and secretion remain unclear. Plasma levels of ghrelin decrease in response to sham feeding (i.e., when a person chews food but does not swallow it), and after administration of a muscarinic blocker. These findings suggest that the secretion of ghrelin, and potentially tht of other appetite-regulating gastrointestinal hormones as well, might be controlled by neural and/or other hormonal factors related to the thought, smell or taste of food. The purpose of this study is to determine whether these neurosensory inputs, that together constitute the "cephalic phase" of feeding, can regulate the release of these gastrointestinal hormones. To test our hypotheses, serum levels of ghrelin, PYY 3-36 and other "gut" hormones related to appetite will be measured in 10 lean and 10 obese but otherwise healthy subjects while fasting, and again every 20 minutes for 140 minutes with each of the following interventions: while resting quietly in a room; observing and smelling a standard meal; observing, smelling, tasting and chewing the standard meal, but not ingesting it; and observing, smelling, tasting, chewing and ingesting the standard meal. HYPOTHESIS 1. The sham-feeding test induces changes in ghrelin levels in lean individuals. 2. These changes also are seen in obese individuals. SPECIFIC AIMS 1. To measure the serum levels of ghrelin, PYY 3-36 and other "gut" hormones related to appetite in 10 lean (BMI 18-25) healthy adults while fasting, and again after each of the following conditions: a. resting quietly in a room; b. observing and smelling a standard meal; c. observing, smelling and tasting the standard meal, but not ingesting it; d. observing, smelling, tasting and ingesting the standard meal. 2. To repeat the same procedure in 10 obese (BMI 30-35), healthy persons. BACKGROUND AND SIGNIFICANCE Ghrelin, a novel gastrointestinal peptide, is thought to increase appetite. In the fasting state the stomach secretes ghrelin, and it is suppressed by food intake or during states of increased sympathatic activation such as hyperthyroidism. When administered to humans, it was found to increase caloric intake. In animal studies, it icnreases food intake, body weight and fat deposition. Ghrelin thus appears to function as a meal-regulated orexigenic signal. In contrast, the gastrointestinal peptide YY 3-36 (PYY 3-36) has been recently proposed as a meal-regulated anorexigenic or satiety signal. This peptide is an agonist of the Y2R receptor. It is released from the gastrointestinal tract in the immediate postprandial state, and it acts centrally in the arcuate nucleus of the hypothalamus to inhibit the release of the orexigenic signal, neuropeptide Y. PYY has been shown to decrease appetite and food intake when administered to humans. Although both ghrelin and PYY are clearly important regulators of meal size, caloric intake, appetite and satiety, the factors that regualte their synthesis and secretion remain unclear. It is likely that the presence of food in the upper gastrointestinal tract is only one of several factors that might regulate their secretion in a reciprocal fashion. Results of a very recent preliminary experiement by Arosio et al. show that plasma levels of ghrelin decrease in response to sham feeding (i.e., when a person chews food but does not swallot it), and after administration of a muscarinic blocker. These provocative findings suggest that the secretion of ghrelin, and potentially that of other appetite-regulating gastrointestinal hormones as well, might be controlled by neural and/or other hormonal factors related to the thought, smell or taste of food. The purpose of this study is to determine whether these neurosensory inputs, that together constitute the "cephalic phase" of feeding, can regulate the release of ghrelin and PYY.