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.
