Role of cholecystokinin in the control of food intake

CCK appears to regulate short-term control of food intake by acting as a satiety signal. Larger doses of CCK may decrease food intake by aversive actions (malaise, nausea, cramps), presumably by effects on gastrointestinal motility. In rats and most likely humans CCK is released from the upper intestine after a mixed meal and appears to activate afferent vagal fibers by causing pyloric contraction with resultant gastric distention or directly binding to the gastric afferent vagus which courses to the nucleus solitarius with further projections to the paraventricular nucleus and ultimately the ventromedial hypothalamus. Peripherally released CCK may also bind to CNS receptors in the area postrema overlying the nucleus solitarius. Central nervous system CCK released from the paraventricular nucleus may also exert a satiety effect. The satiety effect of CCK appears to be a physiologic action of the peptide since antibodies to CCK and CCK receptor antagonists can increase food intake. CCK is probably just one of several satiety signals but can cause a profound decrease in food intake when administered exogenously in pharmacologic doses. Administration of exogenous CCK, as well as endogenous CCK released by oral protease inhibitors, can decrease food intake in humans. Studies designed to examine the effect of chronic administration of CCK on food intake will be necessary to determine if the peptide has a role in the management of obesity and bulimia.