P112: Novel neuropeptide spexin reduces appetite by POMC activation via galanin receptor 2 in mice

Objective: A novel neuropeptide spexin (SPX) is widely expressed in a variety of tissues, and activates galanin receptor 2 (GALR2) and 3 (GALR3). SPX is associated with multiple functions including appetite regulation, however, its precise role is still largely unknown. We investigated the mechanism by which SPX regulates appetite and body weight in C57Bl/6 mice. Methods: Changes of food intake, body weight, and gene expression of neuropeptides in the mediobasal hypothalamus were measured, and a conditioned taste aversion (CTA) test was performed after intra-third ventricular administration (I3V) of SPX (3 and 10 μg), SPX-based GALR2-specific agonist (3 μg) or vehicle in C57BL/6J mice. In addition, changes of body weight and food intake were measured after I3V co-administration of SPX (10ug) and GLAR2 antagonist M871 (10 ug). Results: I3V administration of SPX (10 μg) reduced food intake at 12 and 24 h, and attenuated weight gain with significant elevation of proopiomelanocortin (POMC) mRNA level in the mediobasal hypothalamus compared to vehicle. I3V administration of SPX injection did not result in CTA. Furthermore, I3V administration of SPX-based GALR2-specific agonist (3 μg) decreased food intake and weight gain while I3V administration of SPX at the same dose did not, and co-administration of SPX (10 ug) and GALR2 antagonist M871 (10u g) restored decreased food intake and weight gain by a single treatment with SPX (10 ug), emphasizing the important role of GALR2 in central SPX-induced anorexia. Conclusion: SPX plays an important role in the regulation of food intake, potentially via GALR2 by activating POMC neurons in the mediobasal hypothalamus of mice.