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

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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. 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.