| Objective:To investigate the effect of high frequency (10Hz) VNS on feeding behavior, appetite, peptide secretion in rats fed a high-fat diet, and to explore the mechanisms of VNS on the regulation of feeding and weight.Methods:Adult male Wistar rats were done laparotomy surgery, each implanted subcutaneously with a microstimulator (MS). End of the electrode packaged subdiaphragmal vagus and fed a high-fat diet throughout the entire study period (42days). The left vagus nerve was stimulated by rectangular electrical pulses (10ms,200mV,10Hz,12h a day) generated by the MS. Body weight and food intake were measured each morning. At the end of the experimental period, animals were euthanized and blood samples were taken. Serum levels of ghrelin, leptin and nesfatin-1were assessed using radio immunoassays. Adipose tissue content was evaluated by weighing epididymal fat pads, which were incised at the time of sacrifice. Using immunohistochemical to detecte the expression of c-Fos neurons in solitary nucleus (NTS).Results:Chronic left vagus nerve stimulation significantly decreased food intake(p<0.05), body weight gain (p<0.05)and epididymal fat pad weight(p<0.05) in animals that received VNS compared with control animals. Significant neuronal responses in the NTS were observed following VNS. Finally, compared with control animals and sham group, chronic vagus nerve stimulation group serum concentrations of ghrelin were increased (p<0.05), while serum levels of leptin were decreased (p<0.05). Serum nesfatin-1levels were no change. After left vagus nerve stimulation, bilateral NTS c-Fos immune active cells were significantly increased (P<0.05～0.01), especially the left side (P<0.01).Conclusions:VNS leads to reductions in food intake, body weight gain and adipose tissue by increasing brain satiety signals conducted through the vagal afferents. VNS also evoked a feed-related hormonal response.
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