Reduced appetite and unpleasant feelings from activating GLP-1 receptors involve brainstem neurons controlling digestion and are influenced by activating GIP receptors

Cholecystokinin-expressing neurons in the caudal brainstem are required for the anorectic effects of glucagon-like peptide-1 receptor agonists.

• GLP-1 receptor agonists effectively reduce appetite and body weight through central mechanisms.
• These effects are mediated by cholecystokinin-expressing neurons in the caudal brainstem.
• Cholecystokinin-expressing neurons are necessary for both the appetite reduction and body weight loss associated with GLP-1 receptor agonists.
• GLP-1 receptor agonists also induce conditioned taste avoidance, which involves these neurons.
• Activation of GIP receptors does not directly target cholecystokinin-expressing neurons but reduces their recruitment in response to GLP-1 receptor agonists.

Simplified