Scientists at the University of Cambridge say they have figured out why two opposite approaches to the same brain receptor can both lead to weight loss. The findings, published in Nature Metabolism, could help guide future obesity treatments, according to ScienceDaily.
In mouse experiments, the researchers found that activating the glucose-dependent insulinotropic polypeptide receptor, or GIPR, in the brainstem reduced appetite and body weight. Blocking the same receptor produced a similar weight-loss effect, but through a different area of the brain.
The team used genetically engineered mice to test where the treatments were working by removing GIPR from either the brainstem or the hypothalamus. They then gave the animals combinations of GIPR activators, GIPR blockers and GLP-1 drugs while monitoring food intake, body weight, fat mass and blood sugar control.
According to the study, the brainstem appears to be the main site where GIPR activators work, while GIPR blockers act mainly through the hypothalamus. The researchers also found signs that blocking GIPR could strengthen the effects of some medicines that target the amylin receptor.
The results may help explain why drugs such as MariTide, which is in phase 3 clinical trials, can be effective even though it blocks GIPR rather than activates it. The researchers say understanding these brain pathways could help scientists design obesity medicines that work better alone or in combination.
