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Insulin and Leptin Combine Additively to Reduce Food Intake and Body Weight in Rats

Departments of Biomedical Sciences (E.L.A.), Cell Biology, Neurobiology and Anatomy (E.L.A.) and Psychiatry (S.C.B., D.J.C., R.J.S., S.C.W.), College of Medicine, University of Cincinnati, Cincinnati, Ohio 45267-0555

Leptin and insulin are distinct adiposity signals that regulate food intake and body weight. Because recent evidence suggests that the central catabolic acition of each is mediated by the hypothalamic melanocortin system, we tested the hypothesis that leptin and insulin interact within the brain, either additively or synergistically, to suppress food intake and reduce body weight. Using a within-subjects design, we co-administered leptin and insulin into the 3^rd cerebral ventricle (i.c.v.) over a wide range of doses, and compared the combined effects to what occurred following the administratioin of each peptide alone. The data suggest that leptin and insulin interact sub-additively to regulate food intake and body weight over the first few hours. That is, the ability of combinatins of leptin and insulin to reduce food intake and body weight was less than what would be predicted by the sum of their independent actions. Over 24 hours, however, the combined doses fit a strictly additive model. These data therefore imply a redundancy in the functional intracellular pathways or neuronal circuits that leptin and insulin utilize in the acute regulation of food intake and body weight, and they further imply that over time, the redundancy dissipates.

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