Physiological Low Doses of Leptin and Cholecystokinin Induces Body Weight-Loss in Juvenile and Lean, but not in Adult-Obese Rats

Leptin and cholecystokinin (CCK) are two hormones involved in body weight regulation and feeding behavior. Leptin, an adiposity-derived signal, and CCK, a gut-satiety signal, interact in a synergistic manner and their concomitant treatment causes more weight loss than any hormone administered alone. The synergistic interaction between CCK and leptin has been widely characterized in lean rats, but there are a few studies performed in obese rats. Herein, in the same individual, we compared the sensitivity to CCK, leptin and the combined treatment, leptin + CCK, on body weight and food intake in two experiments one performed in juvenile-lean rats, and in a second experiment comparing adult Chow-fed versus adult-high fat diet (HFD) rats. We found that only the combined treatment had a long-term effect on food intake and caused a substantial and synergistic body weight loss, in juvenile rats. However, the same combined treatment failed to induce weight loss in both Chow-fed and HFD rats. We thus conclude that the sensitivity to leptin + CCK was age dependent, and at the doses used ineffective in adult and obese rats.