Role of neurotensin receptor 1 in the regulation of food intake by neuromedins and neuromedin-related peptides

Central administration of neuromedins and neuromedin-related peptides suppresses food intake in rodents. Neurotensin- and neuromedin U (NMU)-induced anorexia is mainly mediated through neurotensin receptor 1 (Ntsr1) and NMU receptor 2, respectively. Xenin belongs to the neurotensin family and suppresses food intake via an unknown receptor. It has been suggested that Ntsr1 also mediates biological actions of xenin and NMU. Therefore, we examined the effect of intracerebroventricular injection of xenin and NMU on food intake and body weight in wild-type and Ntsr1-deficient mice. The feeding-suppressing and weight gain-inhibiting effects of xenin were abolished in Ntsr1-deficient mice, but NMU reduced food intake and body weight gain in both wild-type and Ntsr1-deficient mice. These findings support the role for Ntsr1 in the mediation of the metabolic effect of xenin as well as neurotensin. Therefore, enhancement of signaling through the Ntsr1 receptor is a potential strategy to reduce appetite and ameliorate obesity.