Electrical chronic vagus nerve stimulation activates the hypothalamic-pituitary-adrenal axis in rats fed high-fat diet.

The brain and the gut communicate bi-directionally through the brain-gut axis. The key role in such interactions plays autonomic nervous system and its major component, the vagus nerve. There is growing evidence that vagus nerve stimulation (VNS) has a suppressive effect on both short- and long-term feeding in animal models. In the present study, we investigated the effect of VNS on the hypothalamic pituitary adrenal axis, feeding behavior and appetite in rats fed a high-fat diet. Adult male Wistar rats were implanted with a microstimulator (MS) and fed a high-fat diet throughout the study (42 days). The left vagus nerve was stimulated subdiaphragmatically by electrical pulses (10 ms, 200 mV, 1 Hz or 10 Hz respectively, 12 h a day) generated by the MS. Daily food intake and body weight were measured. At the end of the experiment, animals were euthanized and serum corticosterone levels were assessed by immunoassays. Adipose tissue content was evaluated by measuring epididymal fat pads' weight. To determine whether VNS activated food-related areas of the brain, neuronal c-Fos induction in the nucleus of the solitary tract (NTS) was assessed. Chronic VNS decreased food intake, body weight gain and epididymal fat pad weight in stimulated animals compared to control animals. Serum corticosterone concentrations were significantly elevated following VNS, and neuronal responses in the NTS were observed. The study demonstrates that chronic electrical VNS exerts anorexigenic effects on food intake and body weight gain, and the hypothalamic pituitary adrenal axis activation may contribute to these effects.