Hormonal
Pharmacologic activation of GIP and GLP-1 receptors rapidly inhibits AgRP neurons, and this neural inhibition contributes to the appetite-suppressing effects of incretin-based obesity therapies.
Incretin-based medications (like semaglutide and tirzepatide) work in part by shutting down hunger-promoting brain cells (AgRP neurons). This mechanism is driven by both GIP and GLP-1 pathways, with dual-action drugs being more effective than single-action ones. This neural inhibition helps explain why these drugs successfully reduce food intake, even in individuals with obesity.
Our results have revealed a role for endogenous GIP in gut-brain appetite regulation and indicate that incretin analogs act in part via AgRP neurons to mediate their anorectic effects.
Why this rating
High-quality in vivo mechanistic evidence using fiber photometry and optogenetics in mice, though not a human clinical trial.
Source
Incretin receptor agonism rapidly inhibits AgRP neurons to suppress food intake in mice
Hayley E. McMorrow et al. · Journal of Clinical Investigation · 2025
DOI 10.1172/jci186652
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