This project will extend our previous demonstration that food intake is reduced by intravenous infusion of cholecystokinin octapeptide (CCK-8) in both nonobese and obese men. Our objectives are to study four related aspects of this pnenomenon: 1) its relation to stomach fullness, 2) its extension to women, 3) its persistance in the reduced obese individual, 4) the effect of endogenously released as opposed to exogenously administered CCK. The first objective will be accomplished by giving subjects different amounts of soup to consume before a main course, simultaneously infusing CCK or saline intravenously, and measuring both plasma CCK levels and gastric emptying of the soup. Our hypothesis is that CCK will be more effective in reducing intake when the stomach is relatively full than when it is relatively empty. Second, this experiment will also tell us whether CCK is effective in women, perhaps even more so than in men. Third, we will compare the effects of intravenous CCK infusions among nonobese, obese, and reduced obese women, to determine whether CCK could be effective in reducing and maintaining weight by causing reduced food intake. Fourth, we will determine, by direct measurement of plasma CCK levels, the effects on CCK release induced by two amino acids, tryptophan and phenylalanine, which are reputed to release CCK. If these substances are found to release CCK in a pattern which mimics that of the exogenous infusion of CCK, we will determine their effects on food intake. The significance of this work is that it will enable us to determine whether CCK could have a practical role in the treatment of obesity, and whether CCK's release could be effected naturally, by nutrients present in foods.
