Regulatory signals from the brain and gut control appetite. Two neuropeptides thought to have a primary role in the hypothalamic feeding centers are neuropeptide Y (NPY), an orexigenic, and cholecystokinin (CCK) a satiety factor. Gut signals appear to act through hypothalamic brain peptides to regulate feeding. Signals sent to the hypothalamus during gastric distension, intestinal passage of nutrients, and postabsorptive sensation of caloric intake, may influence satiety. Unfortunately, the current body of information is not adequate for a full understanding of the neuropeptidergic control of the satiety cascade. Our preliminary experiments in a canine feeding model have begun to clarify some of these central and peripheral satiety signals. This model of cerebroventricular cannulation and true sham feeding in the dog is the basis for the studies detailed in the following seven specific aims: 1. Characterize the central and peripheral effects of NPY on sham feeding and determine whether central NPY is a physiologic stimulator of feeding in the dog. 2. Determine if central NPY is the final event in the initiation of feeding by characterizing its effects against several known satiety signals (i.e., gastric distension, intestinal and intravenous nutrients, central CCK and naloxone). 3. Characterize central CCK's satiety inducing effect against a variety of feeding signals (i.e., starvation, central endorphine and NPY and highly palatable food). 4. Determine whether there is a relationship between the central effect of CCK/NPY on feeding and gastric emptying. 5. Determine whether gastric distension-induced satiety is mediated by the central release of CCK, and if that release is vagal mediated. 6. Determine the effect of intestinal perfusion (jejunal, ileal or colonic) with nutrients (fats, carbohydrates, proteins) on sham feeding. 7. Study the effect of chronic intravenous feeding (fats, carbohydrates, proteins or mixed) versus enteral feeding on sham feeding. From these studies we hope to better understand the relative importance of a variety of signals and eventually construct an integrated satiety cascade. This information is a necessary prerequisite to our understanding of disease processes associated with disturbances in nutrient intake, such as anorexia nervosa and bulemia.

Project Start
1988-12-01
Project End
1993-11-30
Budget Start
1989-12-01
Budget End
1990-11-30
Support Year
2
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Duke University
Department
Type
Schools of Medicine
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705
Geoghegan, J; Pappas, T N (1997) Clinical uses of gut peptides. Ann Surg 225:145-54
Geoghegan, J G; Cheng, C A; Lawson, C et al. (1997) The effect of caloric load and nutrient composition on induction of small intestinal satiety in dogs. Physiol Behav 62:39-42
Lee, M C; Mannon, P J; Grant, J P et al. (1997) Total parenteral nutrition alters NPY/PYY receptor levels in the rat brain. Physiol Behav 62:1219-23
Lawson, D C; Mantyh, C R; Pappas, T N (1994) Effect of CGRP antagonist, alpha-CGRP 8-37, on acid secretion in the dog. Dig Dis Sci 39:1405-8
Mantyh, C R; Vigna, S R; Maggio, J E et al. (1994) Substance P binding sites on intestinal lymphoid aggregates and blood vessels in inflammatory bowel disease correspond to authentic NK-1 receptors. Neurosci Lett 178:255-9
Geoghegan, J G; Lawson, D C; Cheng, C A et al. (1994) Intracerebroventricular neuropeptide Y increases gastric acid secretion by decreasing tonic adrenergic inhibition of acid in dogs. Brain Res 635:118-24
Mantyh, C R; Pappas, T N; Vigna, S R (1994) Localization of cholecystokinin A and cholecystokinin B/gastrin receptors in the canine upper gastrointestinal tract. Gastroenterology 107:1019-30
Lee, M C; Lawson, D C; Pappas, T N (1994) Neuropeptide Y functions as a physiologic regulator of cephalic phase acid secretion. Regul Pept 52:227-34
Geoghegan, J G; Lawson, D C; Cheng, C A et al. (1993) Intracerebroventricular neuropeptide Y increases gastric and pancreatic secretion in the dog. Gastroenterology 105:1069-77
Cheng, C A; Geoghegan, J G; Lawson, D C et al. (1993) Central and peripheral effects of CCK receptor antagonists on satiety in dogs. Am J Physiol 265:G219-23

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