Roux‐en‐Y Gastric Bypass Surgery Increases The Response Of Central Vagal Neurons To Satiety Neuropeptides

Abstract

Roux‐en‐Y gastric bypass surgery (GBS) is the most effective treatment for morbid obesity although the effects on brainstem neurons responsible for vagal control of the viscera are unknown. The aim of the present study was to investigate the effects of obesity and GBS on the pharmacological responses of rat dorsal motor nucleus of the vagus (DMV) neurons.4‐week old Sprague‐Dawley rats were fed a high fat diet (60% kcal from fat) for 44–59 weeks prior to GBS surgery. Sham rats received the same surgical protocol except intestinal manipulation was performed instead. Three weeks post‐surgery, whole‐cell patch clamp recordings were made from DMV neurons in brainstem slices (300μm) and the effects of perfusion with either GLP‐1 or CCK8s (both 100nM) on neuronal excitability were measured.In GBS rats, 5 of 5 neurons tested responded to GLP‐1 with an increase in action potential firing rate (219±35%) whereas only 2 of 9 Sham neurons were similarly responsive (P<0.05). In contrast, while 3 of 6 GBS neurons responded to CCK8s with an increase in firing rate (190±21%) this was not significantly different from the response of Sham neurons (2 of 12 responsive neurons, 230±70%, P>0.05).These results suggest that the effects of GBS to reset obesity‐related alterations in ingestive behavior also involves modulation of the responsiveness of central vagal neurons to gastrointestinal satiety neuropeptides.Supported by NIH DK080899