Novel peptide-peptide cooperation may transform feeding behavior.

There is need for a new approach to the suppression of feeding. Here, we show that two of the most potent endogenous satiety peptides interact in a novel way to cross the blood-brain barrier (BBB) and to suppress food intake. Combined peripheral administration of leptin and urocortin (UCN) significantly decreased food intake, whereas neither one showed an effect when given alone in the same doses. We further provide a mechanism whereby this novel cooperativity can occur by demonstrating that UCN, which by itself does not cross the BBB, can readily enter the brain by associating with leptin. Such a novel interaction between two peptides at the BBB opens new approaches for general study of the dynamic regulatory role of the BBB in brain-body communication as well as the specific study of obesity.