<p>INTRODUCTION</p><p>Xenin is a 25-amino acid peptide identified from human gastric mucosa. Centrally and peripherally administered xenin decreases food intake in rodents. A previous study showed that xenin-induced anorexia was mediated by the neurotensin and CRF receptors. However, the central mechanism of xenin-induced anorexia has been unclear yet. Nesfatin-1/NucB2 (nesfatin-1) is newly identified as an anorexia neuropeptide. We examined the central effects of xenin on food intake, water intake and Nesfatin-1 like immunoreactivity (nesfatin-1-LI) neurons in rat.</p><p>METHODS</p><p>After intracerebroventricular (icv) administration of xenin, we examined the Fos like immunoreactivity (Fos-LI) and nesfatin-1-LI expression by immunohistochemistry in rat brain. We also measured food and water intake, after icv administration of xenin with pretreatment of nesfatin-1 antisense.</p><p>RESULTS</p><p>Fos-LI expressed in the supraoptic nucleus (SON), paraventricular nucleus (PVN), arcuate nucleus, central amygdaloid nucleus, area postrema, and nucleus of the solitary tract after icv administration of xenin. Icv administered xenin caused significant increases the number of Fos-LI in expressing nesfatin-1-LI neurons in the SON and PVN. Furthermore, icv administration of xenin significantly decreased food intake. This xenin-induced food suppression was significantly attenuated by pretreatment with icv administration of antisense nesfatin-1.</p><p>CONCLUSION</p><p>These results indicate that nesfatin-1 may play an important role in xenin-induced food suppression in rats.</p>