Implantable gastric stimulation alters expression of oxytocin- and orexin-containing neurons in the hypothalamus of rats

Background: Implantable gastric stimulation (IGS) has been proposed as a therapeutic option for treating obese patients. We studied the underlying central mechanism behind the reduction of food intake and body weight by gastric electrical stimulation (GES), by studying the expression of anorexigenic and orexigenic-peptide containing neurons in the hypothalamus. Methods: Oxytocin antiserum, orexin antiserum and c-Fos protein-antiserum were used for immunostaining technique. Brain sections were obtained from the control rats and those with 2 hours of GES with parameters typically used in the treatment of obesity in humans. Results: A) 2-hr IGS increased the expression of oxytocin-immunoreactive (IR) neurons in the paraventricular nucleus (PVN, 23.7±1.8 vs 31.1±2.2, P<0.05) and the supraoptic nucleus (SON, 29.0±2.2 vs 39.7±2.5, P<0.01). However, the expression of orexin-IR neurons in the lateral hypothalamic area (LHA) was decreased (27.8±2.6 vs 20.6±1.7, P<0.01). B) The expression of c-Fos positive neurons was increased in the PVN and SON with IGS. A coexistence of oxytocin-IR positive neurons and c-Fos-IR ones in the PVN and SON from the adjacent brain sections was observed, confirming the activation of OT-containing neurons in the PVN and SON following IGS. Conclusion: IGS increases the expression of hypothalamic neurons containing the anorexigenic neuropeptide, oxytocin, and decreases the expression of neurons containing the orexigenic neuropeptide, orexin. This central anorexigenic effect of GES may contribute to the reduced appetite and increased satiety in obese patients with IGS therapy.