Effects of exogenous nesfatin-1 on gastric distention-sensitive neurons in the central nucleus of the amygdala and gastric motility in rats

Nesfatin-1 is a novel brain-gut peptide identified in several brain regions associated with feeding and gastrointestinal function. Our study explored the effects of nesfatin-1 in the central nucleus of the amygdala (CNA) on the activity of gastric distention (GD)-sensitive neurons, gastric motility, and the potential regulation mechanisms by the dorsal motor nucleus of the vagus (DMV). Following retrograde injection of fluorogold (FG) into the DMV, we found that nesfatin-1/FG dual-labeled neurons were detected in the CNA, which indicates that some of the nesfatin-1-immunoreactive neurons arising from the DMV may project to the CNA. Single unit discharges in the CNA were recorded extracellularly, and gastric motility was monitored by implantation of a force transducer into the stomach of conscious rats. These results showed that nesfatin-1 administration to the CNA excited most of the GD-excitatory neurons, inhibited GD-inhibitory neurons, and dose-dependently reduced gastric motility. All of the above effects induced by nesfatin-1 could be partially blocked by pretreatment with the melanocortin 3/4 receptors antagonist, SHU9119. Electrical stimulation of the DMV excited the majority of the nesfatin-1-responsive GD neurons in the CNA. Additionally, pretreatment with an anti-NUCB2/nesfatin-1 antibody in the CNA increased the firing rate of nesfatin-1-responsive GD-inhibitory neurons but decreased the firing rate in nesfatin-1-responsive GD-excitatory neurons following electrical stimulation of the DMV. Finally, a subdiaphragmatic vagotomy eliminated the diminished gastric motility induced by nesfatin-1 injection. Taken together, these findings suggest that nesfatin-1 regulates the activity of GD-sensitive neurons and gastric motility via the melanocortin pathway in the CNA. Furthermore, the DMV may be involved in this regulatory pathway.