Rescue food reward in obesity with neuro-modulation of gut-brain signals

The vagus nerve (VN) carries signals about food from gut to brain. These signals are impacted in animal models of obesity. How does the VN respond to food in humans with and without obesity? Can we modulate this signal to rescue food reward and aid weight loss? The overarching goal of this project is to answer these questions and develop and disseminate an innovative evidence-based, feasible, effective and sustainable intervention in obesity. Approximately two-thirds of the Turkish population has unhealthy body weight and in that group one-third has obesity [1]. Obesity is a gateway disease for developing other chronic health conditions such as cardiovascular disease, diabetes, and cancer. Asian populations have higher health-risks at lower body weights relative to other populations, perhaps due to higher abdominal obesity, which makes the impact of obesity in Turkey higher [2]. The healthcare system in Turkey is universal, so obesity costs the Turkish government tens of millions of Turkish Liras. The service and agriculture sectors give the country a relatively large civilian labor force. As a result, the Turkish economy is sensitive to the pressure of the increasing productivity costs of obesity. Turkish people take pride in health, but obesity is a growing problem that burdens individuals with a reduced quality of life and life expectancy. Popular opinion favors dieting and/or other lifestyle changes like exercise as the best antidote against obesity, but these interventions are usually ineffective in the long term [3,4]. The only method that achieves clinically significant weight-loss in obesity is bariatric surgery. In this surgery the stomach is made smaller among other adjustments. Unfortunately, this procedure is expensive, risky and only available to those with advanced obesity. This means there are practically no options for anyone gaining unhealthy weight. A low-risk, cheap alternative to bariatric surgery is necessary, so interventions can be made available to the entire population with unhealthy weight. One plausible physiological mechanism underlying the success of bariatric surgery is a change in VN function. Interestingly, implantation of a VN stimulation device for treatment of other conditions (like epilepsy or depression) often is accompanied by dramatic weight loss [5]. Recent advances in the treatment of those conditions have identified a non-invasive method for stimulation of the VN (nVNS) via a branch of the nerve in the shell of the outer ear. Here we propose to adapt nVNS for treatment of obesity. There are two major knowledge gaps that hinder immediately application of this method to rescuing food reward. First, we don?t know how the VN responds to food reward in humans. Secondly, the method of nVNS currently used in other conditions may not be optimal for modulating vagal responses to food specifically. We propose a novel approach to these issues by monitoring neural response in the VN ganglions in the neck area with magnetic resonance imaging. More specifically, the research objectives of this project are to: 1) Identify optimal stimulation and observation methods for VN response; 2) Determine the VN response to food in populations with healthy weight, how this response differs in obesity, and if nVNS can be used to make response in obesity resemble response in healthy weight; 3) Test the ability of nVNS to rescue food reward and aid weight loss in populations with obesity; This project will lay the groundwork for this intervention to be commercially scaled up to become available to a large portion of the Turkish population with unhealthy weight with the goal of reducing the personal and societal burden of obesity. The ability to measure VN ganglion responses in humans will be a ground-breaking advance in neuroimaging techniques. We will also educate a new generation of neuroscientists with expertise in neuro-modulation and obesity, advancing Turkey?s eminence in fundamental research.

01.11.2019 – MARIA GERALDINE VELDHUIZEN