Cholecystokinin and leptin act synergistically to reduce body weight.

Leptin, the product of the obese gene, reduces food intake and body weight in rats and mice, whereas administration of the gut-peptide CCK reduces meal size but not body weight. In the current experiments, we report that repeated daily combination of intracerebroventricular leptin and intraperitoneal CCK results in significantly greater loss of body weight than does leptin alone. However, leptin plus CCK treatment does not synergistically reduce the size of individual 30-min sucrose meals during this period, and the effect of leptin-CCK combination on daily chow intake, while significant, is small compared with the robust effects on body weight loss. This synergistic effect on body weight loss depends on a peripheral action of CCK and a central action of leptin. These data suggest a previously unsuspected role for CCK in body weight regulation that may not depend entirely on reduction of feeding behavior and suggest a strategy for enhancing the effects of leptin in leptin-resistant obese individuals.