GUT-BRAIN AXIS: THE ROLE OF GLP1R-VAGAL AFFERENTS IN THE EFFECT OF DIETARY FIBER ON ENERGY BALANCE

The global prevalence of obesity continues to rise, with evidence suggesting that this trend is driven more strongly by dietary intake than by sedentary lifestyle. In parallel, consumption of ultra-processed foods (UPFs) has increased in the same countries experiencing rising obesity rates. UPFs are typically high in sugar and fat but notably low in dietary fiber, which is fermented by the gut microbiota to produce short-chain fatty acids (SCFAs) with key roles in metabolic regulation. Consequently, many UPFs are now reformulated with added fiber, making it essential to understand how this supplementation, and the resulting SCFA production, influences metabolic regulation and feeding behavior. Since SCFAs can directly stimulate glucagon-like peptide 1 (GLP1) production, we hypothesized the fiber-induced SCFA production engages GLP1-dependent gut-brain signaling to promote satiety. To test this, GLP1R-expressing vagal afferents were selectively depleted in mice exposed to a Western- style diet (high fat, high sugar and low fiber) and subsequently supplemented with soluble fiber. Fiber supplementation rapidly increased satiety in control animals without affecting satiation. In contrast, mice lacking GLP1R+ vagal afferents failed to exhibit fiber-induced satiety and instead displayed altered meal termination. These findings identify a critical role for GLP1R-dependent vagal signaling in mediating feeding adaptations to dietary fiber under obesogenic conditions. Ongoing work aims to define the central circuits integrating these gut-brain signals upon fiber nutrition. Overall, the goal is to understand how fiber supplementation in UPFs influences gut-brain signaling to inform obesity prevention strategies and potentially identify new therapeutic targets.