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Background & Aims: Nesfatin-1 is a polypeptide recently discovered in the rat hypothalamus and shown to reduce food intake.The expression ofnesfatin-1 throughout the brain and, in particular, in the nucleus of the solitary tract, a medullary structure with important roles in the regulation of feeding.Nesfatin-1/NUCB2 was shown to co-localize in a high percentage of in medullary catecholamine cell groups which have been shown to be glucose-responsive.In the present study, we evaluated nesfatin-1 action to modulate food intake response upon injection into the dorsal vagal complex (DVC) in freely fed rats during the dark phase.Methods: All rats were surgically implanted with indwelling cannulas in the DVC for microinjection of nesfatin-l.Neuronal activity was recorded extracellularly in order to examine the effects of nesfatin-1 on the glucosensing neurons and the gastric distension (GD) sensitive neurons in the DVC.Results: Nesfatin-1 (15 pM, 25 pM, 50 pM) decreased cumulative food intake by 31.25% (69.23%, 80.00%), 40.91% (52.63%, 57.14%), 28.07% (30.43%, 29.17%), 25.58% (19.44%,30.77%), and 20.19% (15.48%, 27.17%), respectively, compared with vehicle-injected controls at the end of 1,2, 3, 4 and 5 h after nesfatin-1 injection.The 109 neurons were recorded in DVC, of which 31 were activated by glucose and identified as glucose-excited (G-E) neurons;46 were depressed and identified as glucose-inhibited (G-I) neurons;other 32 failed to respond to glucose.Of 26 G-E neurons examined in response to nesfatin-1, 20 were activated, 3 failed to respond to nesfatin-1.Of 39 G-I neurons examined in response to nesfatin-1, 33 were suppressed, 1 was activated, and 5 failed to respond to nesfatin-1.Sixty-nine neurons in the DVC responded to gastric distension (GD), 48 were excited (GD-E), 21 were inhibited (GD-I).32 out of 42 GD-E neurons were excited, whereas 16 out of 18 GD-I neurons were suppressed by nesfatin-l.Conclusion: Nesfatin-1 is involved in the modulation the electric activity of GD-sensitive neurons and glucosensing neurons in DVC.Our data demonstrate that this newly-discovered peptide may exert at least a part of its physiological actions on the control of food intake as a direct result of its role in controlling the excitability of neurons in the DVC.