A study in mice reveals that both activating and blocking the GIPR receptor can trigger weight loss by targeting different regions of the brain.
Key facts
- •The study was conducted by researchers at the Institute of Metabolic Science at the University of Cambridge.
- •Activating GIPR in the brainstem reduces appetite, while blocking it in the hypothalamus increases the effectiveness of fullness signals.
- •The research involved genetically engineered mice with GIPR removed from specific brain regions.
- •Findings suggest GIPR antagonists could improve the efficacy of other obesity treatments, such as those targeting the amylin receptor.
- •The research was funded by the Medical Research Council and Wellcome.
Researchers at the University of Cambridge have discovered why both activating and blocking the GIPR receptor can lead to weight loss. By studying mice, the team found that activating the receptor in the brainstem reduces appetite, while blocking it in the hypothalamus enhances fullness signals. These findings, published in Nature Metabolism, offer new insight into how obesity medications function and could inform the development of more effective combination therapies.
Targeting Different Brain Regions
To determine how GIPR-targeted drugs work, scientists used genetically engineered mice lacking the receptor in specific brain areas. The experiments showed that GIPR agonists, which activate the receptor, primarily function through the brainstem to reduce food intake. Conversely, GIPR antagonists, which block the receptor, promote weight loss through the hypothalamus. In the hypothalamus, the GIPR receptor acts as a 'brake' on signals indicating satiety. By blocking this receptor, the treatment releases the brake, allowing the brain to respond more strongly to signals that the body is full.
Implications for Future Obesity Treatments
The study suggests that GIPR antagonists could be paired with other medications, such as those targeting the amylin receptor or GLP-1 receptors, to enhance weight loss outcomes. This mechanism explains the effectiveness of drugs like MariTide, which is currently in phase 3 clinical trials and combines GIPR antagonism with GLP-1 receptor activation. Dr. Jo Lewis, the study's first author, noted that these findings highlight the brain's central role in obesity treatment. By identifying specific brain circuits involved in these processes, researchers aim to design drugs that provide greater weight loss with fewer side effects.
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This article was independently rewritten by ManyPress editorial AI from reporting originally published by ScienceDaily.
