Scientists at the University of Cambridge found a surprising trick in the brain that can help people lose weight.
They studied mice and learned that a single brain receptor, called GIPR, can be used in two opposite ways. Turning the receptor on in one part of the brain makes mice eat less. Turning the same receptor off in another part also makes them lose weight, but through a different route.
Why the brain matters for weight loss
More than a billion people worldwide have obesity, which raises the risk of diabetes, heart disease, and cancer. Losing weight can lower these risks, yet diet and exercise alone are often not enough.
Modern drugs that talk to the brain
New weight‑loss medicines work by touching brain receptors that control hunger. Drugs such as Wegovy and Ozempic activate a receptor called GLP‑1R, which tells the body to eat less and use sugar better.
Other medicines also target a second receptor, GIPR. Some activate it (like Mounjaro), while others block it (like MariTide). Both actions can lead to weight loss, even though they seem opposite.
Finding the brain region that matters
The Cambridge team used special mice that lacked GIPR in specific brain areas. One group missed the receptor in the brainstem, a spot that helps control appetite and nausea. Another group missed it in the hypothalamus, a region that sets hunger signals.
When the scientists gave the mice a GIPR activator, only the mice with a normal brainstem lost weight. This showed that turning the receptor on works mainly through the brainstem.
How blocking the receptor helps
When they gave a GIPR blocker, the mice without GIPR in the hypothalamus did not lose weight, while normal mice did. This means the blocker works by releasing a “brake” in the hypothalamus, letting fullness signals be stronger.
The researchers also saw that blocking GIPR can make other drugs, such as those aimed at the amylin receptor, work even better.
What this means for future medicines
Understanding that the same receptor can be used in two different brain areas helps explain why drugs like MariTide (which blocks GIPR and activates GLP‑1R) are effective.
Scientists can now think about mixing drugs that act on these separate pathways to create more powerful obesity treatments.
"The brain is a key player in fighting obesity," the study said. "Weight‑loss drugs act on clear brain circuits that control how much we eat."