Opposite Actions on the Same Brain Receptor Both Reduced Food Intake in Mice, Cambridge Team Reports

Activating the glucose-dependent insulinotropic polypeptide receptor, known as GIPR, in the brainstem reduced food intake. MariTide, an investigational drug in phase 3 trials that pairs GLP-1 receptor agonist peptides with an antibody that blocks GIPR, does the opposite. To test where the difference lies, the team used genetically engineered mice and selectively removed GIPR from different brain regions. This work was done in mice, and mouse metabolic physiology differs from human physiology in ways that have derailed obesity drug candidates before. In mice, activating GIPR in the brainstem and blocking it in the hypothalamus both reduced food intake, through different circuits.