The long range goal of this project is to elucidate the mechanisms by which the gut peptide cholecystokinin (CCK) interacts with the stomach and with nutrients to reduce food intake in man, and ultimately to use this knowl- edge for controlling food intake In obesity. One hypothesis to be tested is that administration of CCK in conjunction with a preload (item of food, fluid, or bulk consumed before a main meal) can reduce the intake of the meal by an amount which exceeds the energy in the preload. If the hypothesis is correct, the combination of CCK and preloads could then be utilized in weight control to reduce food Intake without increasing hunger. Another hypothesis is that CCK's intake reducing effect, in conjunction with food, involves delay of gastric emptying. In the present revision, the shape of the dose-effect relation of soup preloads to test meal Intake is determined (Experiment 1) and the effect of CCK infusion on the shape of that relation is analyzed (Experiments 4 and 5). In addition the relationship between fullness of the stomach and food intake is determined by measuring gastric emptying of the preload. The effects of CCK infusion on the satiating effects of nutritive and nonnutritive preloads will also be tested (Experiment 6). The possibility that CCK is released by the preload will be tested by measuring levels of CCK after preloads (Experiment 3). These experiments will enable initial exploration of the mechanisms by which CCK interacts with food to reduce food intake. These mechanisms will be tested by having human subjects consume preloads which fill the stomach by different amounts and by simultaneously giving different amounts of CCK (Experiments 2). In addition, measurements of gastric pressure, and sensations of fullness, satiety, and hunger will be made during inflation of a balloon in the stomach with and without CCK infusion. These measurements (experiments 7A and 7B) will enable us to test the hypothesis that CCK may reduce food intake by simultaneously relaxing the stomach and, paradoxically, increasing the signal of fullness, resulting in enhanced perception of satiety, rather than decreasing the signal of fullness as would ordinarily be expected from a relaxed stomach.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK036507-05
Application #
3234954
Study Section
Biopsychology Study Section (BPO)
Project Start
1986-02-01
Project End
1995-04-30
Budget Start
1993-05-01
Budget End
1994-04-30
Support Year
5
Fiscal Year
1993
Total Cost
Indirect Cost
Name
St. Luke's-Roosevelt Institute for Health Sciences
Department
Type
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10019
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Kissileff, Harry R; Carretta, Julie C; Geliebter, Allan et al. (2003) Cholecystokinin and stomach distension combine to reduce food intake in humans. Am J Physiol Regul Integr Comp Physiol 285:R992-8
Kissileff, H R; Guss, J L (2001) Microstructure of eating behavior in humans. Appetite 36:70-8
Guss, J L; Kissileff, H R (2000) Microstructural analyses of human ingestive patterns: from description to mechanistic hypotheses. Neurosci Biobehav Rev 24:261-8
Wentzlaff, T H; Guss, J L; Kissileff, H R (1995) Subjective ratings as a function of amount consumed: a preliminary report. Physiol Behav 57:1209-14
Muurahainen, N E; Kissileff, H R; Pi-Sunyer, F X (1993) Intravenous infusion of bombesin reduces food intake in humans. Am J Physiol 264:R350-4
Geary, N; Kissileff, H R; Pi-Sunyer, F X et al. (1992) Individual, but not simultaneous, glucagon and cholecystokinin infusions inhibit feeding in men. Am J Physiol 262:R975-80
Melton, P M; Kissileff, H R; Pi-Sunyer, F X (1992) Cholecystokinin (CCK-8) affects gastric pressure and ratings of hunger and fullness in women. Am J Physiol 263:R452-6
Muurahainen, N E; Kissileff, H R; Lachaussee, J et al. (1991) Effect of a soup preload on reduction of food intake by cholecystokinin in humans. Am J Physiol 260:R672-80
Muurahainen, N; Kissileff, H R; Derogatis, A J et al. (1988) Effects of cholecystokinin-octapeptide (CCK-8) on food intake and gastric emptying in man. Physiol Behav 44:645-9