Cholecystokinin and leptin act synergistically to reduce body weight

Leptin, the prod uct of the obese gene, reduces food intake and body weight in rats and mice, whereas administration of the gut-peptide CCK reduces me al size but not body weight. In the current experiments, we report that rep eated daily combination of intracerebroventricular leptin and intraperitone al CCK results in significantly greater loss of body weight than does lepti n alone. However, leptin plus CCK treatment does not synergistically reduce the size of individual 30-min sucrose meals during this period, and the ef fect of leptin-CCK combination on daily chow intake, while significant, is small compared with the robust effects on body weight loss. This synergisti c effect on body weight loss depends on a peripheral action of CCK and a ce ntral action of leptin. These data suggest a previously unsuspected role fo r CCK in body weight regulation that may not depend entirely on reduction o f feeding behavior and suggest a strategy for enhancing the effects of lept in in leptin-resistant obese individuals.