Intestinal Electrical Stimulation Alters Hypothalamic Expression of Oxytocin and Orexin and Ameliorates Diet-Induced Obesity in Rats.

Abstract

Intestinal electrical stimulation (IES) has been proposed as a potential treatment for obesity. The aim of this study was to explore the central mechanism underlying the reduction of food intake and body weight by IES by studying the expression of anorexigenic- and orexigenic-peptide-containing neurons in the hypothalamus. Diet-induced obese (DIO) rats were divided into three groups to receive sham, IES, and pair-feeding for 4weeks. Food intake was measured automatically and presented as daily and body weight measured weekly. The expressions of oxytocin, an anorexigenic neuropeptide, in the paraventricular nucleus of the hypothalamus (PVN) and the supraoptic nuclei of the hypothalamus (SON) and orexin-A, an orexigenic neuropeptide, in the lateral hypothalamic area (LHA) were studied using immunohistochemistry. Compared with sham, IES reduced daily food intake by 28.3% at week 1, 35.6% at week 2, 15.6% at week 3, and 27.1% at week 4. Consistently, IES reduced body weight by 6.3%, compared with a weight gain of 7.2% in sham, and a slight weight loss of 0.5% in pair-feeding. Compared with sham, IES increased the expression of oxytocin-immunoreactive neurons in PVN and SON. Compared with sham, IES decreased the expression of orexin-immunoreactive neurons in LHA. Rats with pair-feeding also showed a relative decease in weight without any changes in the central hormones. IES reduces food intake and body weight and improves glucose tolerance and insulin sensitivity in DIO rats. Its central mechanisms involve enhancement of anorexigenic peptides and suppression of orexigenic peptides in the hypothalamus.