Scientists solve the mystery of a brain “switch” that can trigger weight loss in opposite ways
Scientists have uncovered why two seemingly opposite ways of targeting the same brain receptor can both promote weight loss. In mice, activating the GIP receptor in the brainstem reduced appetite, while blocking it in the hypothalamus removed a kind of “brake” on fullness signals. The discovery helps explain why very different obesity drugs can achieve similar results and suggests that carefully…
Cambridge scientists have unraveled the puzzling phenomenon where activating and blocking the same brain receptor can lead to weight loss in opposite ways. The study, published in Nature Metabolism, found the outcome depends on which part of the brain receives the treatment. According to the findings, activating the receptor in the brainstem reduces appetite, while blocking it in the hypothalamus promotes weight loss through a different mechanism.
Obesity affects over a billion people worldwide, increasing the risk of diseases like type 2 diabetes, cardiovascular disease, and cancer. The brainstem and hypothalamus are key areas involved in regulating appetite and body weight. Recent obesity medications target specific receptors, including the glucagon-like peptide 1 receptor (GLP-1R) and the glucose-dependent insulinotropic polypeptide receptor (GIPR), to reduce food intake and promote weight loss.
However, GIPR can act in opposing ways when activated or blocked, depending on whether it's in the brainstem or hypothalamus. The Cambridge researchers discovered that GIPR agonists primarily work in the brainstem, reducing appetite and leading to lower body weight. Conversely, blocking GIPR in the hypothalamus acts as a brake on fullness signals, allowing them to have a stronger effect and promoting weight loss.
Combining GIPR antagonists with GLP-1 receptor agonists, as seen in some emerging obesity medications, may further enhance weight loss effects. Dr. Jo Lewis, the study's lead author, explained that understanding these distinct brain pathways could help develop more effective and safer obesity treatments that work well in combination with other drugs.
The research underscores the crucial role of the brain in regulating appetite and weight, moving beyond the traditional focus on the gut or pancreas.
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