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的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 摘要 在禁食状态下，胃分泌Ghrelin，一种新的胃肠道肽，它被食物摄入抑制。 当给予人类时，发现它会增加热量摄入。 在动物研究中，它会增加食物摄入量，体重和脂肪沉积。 相反，最近已经提出胃肠道肽YY 3-36（PYY 3-36）是膳食调节的饱腹感信号。 它在餐后立即从胃肠道释放，并抑制食欲信号神经肽Y的释放。 虽然生长激素释放肽和PYY都是热量摄入和食欲的重要调节因子，但调节其合成和分泌的因素仍不清楚。 饥饿素的血浆水平响应于假喂食而降低（即，当人咀嚼食物但不吞咽时），以及在施用毒蕈碱阻断剂之后。 这些发现表明，生长激素释放肽的分泌，以及其他可能调节食欲的胃肠激素的分泌，可能是由神经和/或其他与食物的思想，气味或味道有关的激素因素控制的。 本研究的目的是确定这些神经感觉输入，共同构成的“头阶段”的喂养，可以调节这些胃肠激素的释放。 为了检验我们的假设，将在10名瘦的和10名肥胖的但在其他方面健康的受试者中测量饥饿素、PYY 3-36和其他与食欲相关的“肠道”激素的血清水平，同时禁食，并且每隔20分钟测量一次，持续140分钟，同时进行以下干预：在房间里安静地休息;观察和闻标准餐;观察、闻、尝、嚼标准餐，但不摄入;观察、闻、尝、嚼、摄入标准餐。 假设 1. 假喂养试验诱导瘦个体生长激素释放肽水平的变化。 2. 这些变化也见于肥胖个体。 具体目标 1. 测量10名瘦型（BMI 18-25）健康成年人空腹时以及在以下每种情况下再次测量胃饥饿素、PYY 3-36和其他与食欲相关的“肠道”激素的血清水平： a.在房间里安静地休息; B.观察并闻一闻标准的食物; C.观察、嗅闻和品尝标准餐，但不吃; D.观察、闻、尝和消化标准餐。 2. 在10名肥胖（BMI 30-35）健康人中重复相同的程序。 背景和意义 Ghrelin是一种新型的胃肠道肽，被认为可以增加食欲。 在禁食状态下，胃分泌胃饥饿素，它被食物摄入或在交感神经激活增加的状态下（如甲状腺功能亢进症）抑制。 当给予人类时，发现它会增加热量摄入。 在动物研究中，它增加食物摄入量，体重和脂肪沉积。 因此，Ghrelin似乎起着膳食调节食欲信号的作用。 相比之下，胃肠道肽YY 3-36（PYY 3-36）最近被提出作为膳食调节的促食欲或饱腹感信号。 该肽是Y2 R受体的激动剂。 它在餐后立即从胃肠道释放，并在下丘脑弓状核中枢作用，以抑制食欲信号神经肽Y的释放。 PYY已被证明在施用于人类时降低食欲和食物摄入。 虽然Ghrelin和PYY都是膳食量、热量摄入、食欲和饱腹感的重要调节因子，但调节其合成和分泌的因素仍不清楚。 上消化道中食物的存在可能只是以相互作用的方式调节其分泌的几个因素之一。 阿罗西奥等人最近的初步实验结果表明，饥饿素的血浆水平响应于假喂食而降低（即，当一个人咀嚼食物但不吞咽时），以及在施用毒蕈碱阻断剂之后。 这些令人激动的发现表明，生长激素释放肽的分泌，以及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。 本研究的目的是确定这些神经感觉输入，共同构成了“头相”的喂养，可以调节释放的ghrelin和PYY。

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.