Anorectic and aversive effects of GLP-1 receptor agonism are mediated by brainstem cholecystokinin neurons, and modulated by GIP receptor activation

Nov 29, 2021Molecular metabolism

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

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Abstract

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.

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