The basis of improved glycemic control after bariatric surgery – insights from rodent models

Bariatric surgery has now been accepted as a front-line treatment for type 2 diabetes (T2D) that compares favourably with lifestyle and medicinal interventions. However, the detail of the mechanisms underlying the profound effect of surgery on glucose regulation remains elusive. An understanding of the physiological mechanisms subserving surgical success will allow its replacement with non-surgical approaches - this is the basis of the current application. Our lab has generated preliminary data from a rodent model of vertical sleeve gastrectomy (VSG) which indicates that brown adipose tissue (BAT) is not only necessary for VSG-induced weight loss but is a major contributor to the sequestration of glucose that underpins the improved glucose regulation immediately after VSG. In addition, there is developing evidence that vagal afferent neurons (VANs) are important in relaying sensory information from the gut to the brain to promote the recruitment of BAT. This project aims to understand the nature of changes in glucose regulation following VSG (prior to weight loss), particularly those attributable to effector organs such as BAT. Specifically, this project will evaluate, using in vivo chemogenetic and optogenetic techniques, the extent to which specific vagal afferent neurons contribute to the resolution of T2D after VSG.