Mechanisms underlying the efficacy of bariatric surgery – the role gut-brain interactions in the recruitment of brown adipose tissue

Currently the only available effective and durable treatment for morbid obesity is bariatric surgery. Vertical Sleeve Gastrectomy (VSG) is the most widely performed bariatric surgery and it confers both significant weight loss and improved glucose regulation. However, it is agreed that there is a need for viable alternative approaches. Bariatric surgery has small, but well established, attendant risks, including elevated morbidity and even mortality, irreversibility, cost, and surgical wait times. There is also a pervasive and justifiable view that extensive resectional surgery is an inappropriate endpoint to combat obesity. To identify alternatives, an understanding of the physiological underpinnings of the efficacy of procedures like VSG is required. The vagus nerve is an important conduit for information transfer between the gut and brain that underpins some of the efficacy of VSG. Our data, derived from a rat model of VSG, indicate that an increase in energy expenditure via brown adipose tissue (BAT) contributes substantially to the weight loss in VSG. In the proposed experiments, we aim to establish whether vagal afferent neurons are necessary for the efficacy of the VSG surgery and interrogate the role of these neurons in the mediation of the VSG-induced thermogenic response and promotion of weight loss. This will be accomplished in a number of projects that use cutting edge, optogenetic and chemogenetic approaches. The potential to not only characterise the basis of the efficacy of VSG, but to identify the means by which it can be enhanced, has the potential to change the way in which this mainstay of obesity treatment is viewed and practiced. An understanding of the essential physiological drivers of the procedure also opens the possibility of mimicking, then exploiting, these mechanisms in a non-surgical medical setting.