Roux‐en‐Y gastric bypass reverses the effects of diet‐induced obesity to inhibit the responsiveness of central vagal motoneurones

Key points • Diet‐induced obesity (DIO) is known to alter the biophysical and pharmacological properties of gastrointestinal vagal afferent (sensory) neurones and fibres. • Little information is available, however, regarding the effects of DIO on the properties of central neurones involved in vagally mediated visceral reflexes. • The present study was designed to test the hypothesis that DIO alters the biophysical, pharmacological and morphological properties of vagal efferent motoneurones and that these alterations would be reversed following weight loss induced by Roux‐en‐Y gastric bypass. • Our data indicate that DIO decreases the excitability of vagal efferent neurones and attenuates their responses to the satiety neurohormones cholecystokinin and glucagon‐like peptide 1. These DIO‐induced changes were reversed following Roux‐en‐Y gastric bypass, suggesting that the alterations were due to obesity, rather than diet. These findings represent the first direct evidence that Roux‐en‐Y gastric bypass improves the functioning and responsiveness of central vagal neurocircuits by reversing some of the effects induced by DIO. Diet‐induced obesity (DIO) has been shown to alter the biophysical properties and pharmacological responsiveness of vagal afferent neurones and fibres, although the effects of DIO on central vagal neurones or vagal efferent functions have never been investigated. The aims of this study were to investigate whether high‐fat diet‐induced DIO also affects the properties of vagal efferent motoneurones, and to investigate whether these effects were reversed following weight loss induced by Roux‐en‐Y gastric bypass (RYGB) surgery. Whole‐cell patch‐clamp recordings were made from rat dorsal motor nucleus of the vagus (DMV) neurones in thin brainstem slices. The DMV neurones from rats exposed to high‐fat diet for 12–14 weeks were less excitable, with a decreased membrane input resistance and decreased ability to fire action potentials in response to direct current pulse injection. The DMV neurones were also less responsive to superfusion with the satiety neuropeptides cholecystokinin and glucagon‐like peptide 1. Roux‐en‐Y gastric bypass reversed all of these DIO‐induced effects. Diet‐induced obesity also affected the morphological properties of DMV neurones, increasing their size and dendritic arborization; RYGB did not reverse these morphological alterations. Remarkably, independent of diet, RYGB also reversed age‐related changes of membrane