Does obesity need a vagal reset?

Vagal gut-brain communication is essential for the normal control of eating.

In obesity, however, the sensitivity of vagal neurons to food is blunted, resulting in larger meals and disrupted eating patterns.

But no current therapies aim to restore vagal gut-brain communication in obesity.My research project proposes to seize this missed opportunity: I hypothesize that the loss of vagal sensitivity to food in obese rats results from vagal gene expression changes that can be reversed to induce weight loss.Hence, my overall aim is to induce weight loss in diet-induced obese rats by normalizing vagal gut-brain communication.In the two first parts of this project (years 1-3), I will characterize the functional and molecular changes associated with obesity in vagal afferents.

For this, I will use in vivo fibre photometry to compare vagal sensitivity to food stimuli in lean and obese rats, and single-cell RNA sequencing of vagal neurons to pinpoint the molecular pathways affected by obesity.

In the third part of the project (years 3-4), I will investigate the causality between molecular and functional vagal alterations: for this, I will test whether normalizing the expression of vagal genes in obese rats resets vagal sensitivity to food and results in weight loss.I will conduct this project (100%) with a PhD and a Master student at the Institute of Neuroscience and Physiology of Gothenburg University.

The necessary equipment and collaborations are already in place.