Dissecting vagal mechanisms to untangle homeostatic and reward processes in obesity – HERO

The regulation of feeding behavior relies on the integration of both metabolic and reward signals, which collectively ensure adaptive strategies to maintain body homeostasis. However, our modern food environment and the overconsumption of palatable energy-dense food constantly challenges such strategies and can lead to obesity. Indeed, the latest alarming estimations of the World Health Organization (WHO) reveal that in Europe over half of all men and women are overweight, and roughly one-third are obese. While some genetic traits (monogenic causes) have been identified and extensively studied, it is widely recognized that the metabolic syndrome is in essence a multifactorial and multidimensional disorder that encompass complex networks of, yet unclear, feed-forward physiopathological maladaptations.
Emerging evidence indicates that obesity may result from a maladapted communication between peripheral organs and the brain. Here, supported by studies and current results, we tackle the hypothesis that the interoceptive gut-brain vagal axis, a rapid relay of viscerotopic information toward the brain, may represent a key site of such maladaptive distortion and may scale obesity-associated metabolic and reward dysfunctions.
This project is built upon three main aims:
(1) Establishing the role of gut-brain vagal afferents in scaling the adaptive responses of the reward circuit in obesity: from feeding to nutrients-sensing
(2) Interrogating the gut-brain vagal axis to restore hedonic and metabolic functions
(3) Leveraging the molecular signature of vagal neurons to identify new targets for obesity
Using multi-scale in vivo approaches (from networks to targeted pharmacology to molecular cartography), HERO promotes a novel conceptual framework that sees in the vagal axis a functional element to (i) explore new integrative mechanisms underlying obesity and (ii) establish innovative therapeutic strategies for obesity-induced homeostatic and reward dysfunctions.