Salmon calcitonin - a potent inhibitor of food intake in states of impaired leptin signalling in laboratory rodents

To compare the anorectic effectiveness of leptin and the amylin analogue salmon calcitonin (sCT), rodents were treated on I day with subcutaneous injections. In chow-fed C57Bl/6J mice, leptin and sCT reduced energy intake and acted additively. After C57Bl/6J mice had become leptin-resistant on being fed chocolate as a palatable high-caloric supplement to chow, their sCT-induced decrease in energy intake was more pronounced than in chow-fed mice with differential changes in the intake of chocolate (strong reduction) and chow (slight increase). Dose-response relationships for sCT-induced reductions in energy intake were analysed in chow-fed C57Bl/6J mice and two obese strains, ob/ob mice and melanocortin-4 receptor knockout (MC4-r-KO) mice, as well as in wild-type and fatty (fa/fa) rats. Compared to C57Bl/6J mice, reduction in food intake induced by sCT was attenuated in MC4-r-KO mice, and nearly absent in ob/ob mice, over the dose range investigated. Compared to C57Bl/6J mice, wild-type rats responded more sensitively to sCT and its efficiency was only slightly reduced in fatty (fa/fa) rats. Thus, while genetically induced failures of leptin signalling reduce the action of sCT, it effectively inhibits the intake of a palatable, high fat-high sugar diet even in states of diet-induced obesity with functional leptin resistance.