A role for glucagon-like peptide-1 in the central regulation of feeding

THE sequence of glucagon-like peptide-(1) (7-36) amide (GLP-1) is completely conserved in all mammalian species studied, implying that it plays a critical physiological role(1). We have shown that GLP-1 and its specific receptors are present in the hypothalamus(2,3). No physiological role for central GLP-1 has been established. We report here that intracerebroventricular (ICV) GLP-1 powerfully inhibits feeding in fasted rats, ICV injection of the specific GLP-1-receptor antagonist, exendin (9-39)(4), blocked the inhibitory effect of GLP-1 on food intake. Exendin (9-39) alone had no influence on fast-induced feeding but more than doubled food intake in satiated rats, and augmented the feeding response to the appetite stimulant, neuropeptide Y. Induction of c-fos is a marker of neuronal activation(5). Following ICV GLP-1 injection, c-fos appeared exclusively in the paraventricular nucleus of the hypothalamus and central nucleus of the amygdala, and this was inhibited by prior administration of exendin (9-39). Both of these regions of the brain are of primary importance in the regulation of feeding(6). These findings suggest that central GLP-1 is a new physiological mediator of satiety.