Glucose-dependent insulinotropic polypeptide receptor (GIPR) signalling in oligodendrocyte cells in the brain increases the weight loss action of anti-obesity medicines.

The next-generation of obesity medicines harness the activity of glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 receptors (GIPR, GLP-1R), but exactly how they work remains unclear.

A recent study published in Cell Metabolism and led by Dr Robert Hansford (PhD student with the Blouet group) and colleagues at the IMS-MRL, has shed light on their mechanism of action.

Glucose-dependent insulinotropic polypeptide (GIP) is a gut hormone released in response to the ingestion of glucose and fat. Working with mice, the study team has found that GIP receptors (GIPRs) are found in brain cells called oligodendrocytes and action on these cells enhances the effects of drugs like Mounjaro^TM (and other weight loss drugs which target GIPRs in the brain). GIPRs help these drugs access the brain to reduce hunger and boost weight loss and without them, the drugs are less effective.

These findings have therefore identified a novel mechanism by which incretin therapies may function to promote synergistic weight loss in the management of obesity.

Hansford et al., Glucose-dependent insulinotropic polypeptide receptor signaling in oligodendrocytes increases the weight-loss action of GLP-1R agonism, Cell Metabolism (2025), https://doi.org/10.1016/j.cmet.2025.07.009