Effects of peripheral or central GLP-1 receptor blockade on leptin-induced suppression of appetite.

Leptin and glucagon-like peptide-1 (GLP-1) were proved to act in concert to control the activity of feeding centres. Since leptin receptor was identified in the gut endocrine L cells and neurons producing GLP-1, we have checked whether GLP-1 mediates the effects of leptin on feeding and drinking behaviour. To this aim, an intraperitoneal or intracerebroventricular injection of exendin (9 - 39), a GLP-1 antagonist, (50 or 10 microg per rat, respectively) followed by leptin (100 or 5 microg per rat, respectively) was made and 24-hour food intake and body weight changes were measured. Previous injection of exendin (9-39) completely abolished the supressory effect of peripheral leptin on food intake and body weight gain. Moreover, exendin (9-39) significantly attenuated the effect of intracerebroventricular leptin on food but not water consumption. It is concluded that intact GLP-1 signalling is necessary to mediate the effect of leptin on food intake in the rat. Conversely, leptin seems to affect the thirst center function independently of GLP-1. Also, these findings produce further evidence for close interactions between long- and short-term factors regulating the activity of feeding centres.