Cambridge researchers map brain regions that let opposite GIP-receptor actions both cut weight
A Cambridge team discovered that activating the GIP receptor in the brainstem and blocking it in the hypothalamus each lead to weight loss in mice, explaining why different obesity drugs can work alike.
Scientists at the University of Cambridge’s Institute of Metabolic Science have clarified why two opposite strategies—activating or blocking the same brain receptor—both promote weight loss. In mouse models, stimulating the GIP receptor in the brainstem curbed food intake, whereas inhibiting the receptor in the hypothalamus removed a restraint on satiety signals, yielding similar reductions in body weight. By engineering mice lacking the receptor in specific brain regions, the team mapped these divergent pathways.
The work also revealed that combining GIP-targeted compounds with GLP-1 receptor agonists, like those used in Wegovy and Ozempic, may produce stronger effects, and that GIP antagonists could enhance amylin-based treatments. Lead author Jo Lewis emphasized that understanding these circuits can guide the design of more potent, side-effect-friendly obesity medicines. The research was funded by the Medical Research Council and Wellcome and appears in Nature Metabolism.
Why it matters
It explains how different obesity drugs work and could lead to more effective weight-loss therapies.
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