A new study shows that oral GLP-1 receptor agonists can curb pleasure-driven eating in mice by acting on a brain reward circuit. The research, supported by the National Institutes of Health, examined drugs including orforglipron and danuglipron.
Researchers at the University of Virginia found that these small-molecule drugs activated the central amygdala, a region involved in desire and reward. This activation reduced dopamine release during hedonic feeding, or eating for enjoyment rather than energy needs.
The findings come from experiments on gene-edited mice designed to have human-like GLP-1 receptors. The drugs also influenced areas tied to appetite regulation, but the effect on the deeper reward circuit was previously unrecognized.
"We've known that GLP-1 drugs suppress feeding behavior driven by energy demand. Now it seems oral small-molecule GLP-1s also dial back eating for pleasure by engaging a brain reward circuit," said co-corresponding author Ali Guler.
Lorenzo Leggio of the National Institute on Drug Abuse noted the importance of understanding these mechanisms as medication access grows. The study was published in Nature and was not a clinical trial.
