The long term goal of this research is to apply knowledge of the molecular factors controlling food intake in animals for discovering new ways to help humans limit their food intake. Therefore, food intake will be studied in humans under situations analogous to those which have been shown to lower food intake in animals. A key hypothesis developed from work in animals is that fullness of the stomach combined with intestinal chemostimulation that release cholecystokinin (CCK) can be a powerful combination for reduction of food intake. CCK is released in response to digestion products shortly after a meal starts and participates in the satiating processesa that inhibit eating. CCK has been shown to inhibit food intake in animals best, and in humans possibly only after some food has already been eaten. The goal of this work now is to establish the mechanism of, and optimal conditions for, CCK's food intake-reducing action, so that ultimately it may have therapeutic benefit for those who need to limit food intake. Low energy containing CCK secretagogues which could be given by mouth, under optimal conditions, would be useful in helping those who need to curb food intake, such as diabetics, bulimics, or individuals who must maintain reduced weights and thereby prevent obesity, which is a major risk factor for cardiovascular disease, diabetes and stroke. The proposed work is needed in order to identify the stimuli in the prior food consumption that enhanced CCK's effectiveness for inhibition of food intake. The working hypothesis is that CCK augments food intake-inhibiting action of gastric distention more than it augments the food intake-inhibiting action of tase (i.e., by inducing taste aversion or fatigue with the food's flavor), or intestinal chemostimulation. In order to test the hypothesis, food intake will be measured at test meals after CCK or saline (control) infusion, or CCK's augmented endogenous release, combined with different types of meals, premeal stimulation by food, gastric distention by ballon and gastric and intestinal stimulation by nutrient infusion. These meals will be eaten under controlled conditions, as in laboratory animals. To rule out the possibility that the food intake inhibitory effects are induced by lamaise, rather than satisfaction with eating (i.e., satiety), a newly developed questionnaire, which can discriminate these two modes of intake inhibition, will be employed.
