Los Angeles: Scientists have discovered a destructive brain mechanism that prevents the neurons from signaling that the stomach is full, causing one to overeat.
Researchers found that mice fed a high-fat diet produce an enzyme named MMP-2 that clips receptors for the hormone leptin from the surface of neuronal cells in the hypothalamus.
This blocks leptin from binding to its receptors, which in turn keeps the neurons from signaling that your stomach is full and you should stop eating. This is the first time that a destructive molecular mechanism has been observed and described.
Scientists showed that when MMP-2 is blocked, leptin can still bind to the receptors and signal satiety. They hope that in the future, clinicians will be able to treat leptin resistance in humans by blocking MMP-2. They also have evidence that their findings have a broader scope.
"We need to ask what other pathways, in addition to leptin and its receptors, undergo a similar destructive process and what the consequences might be," said Rafi Mazor, a research scientist at the University of California San Diego in the US.
While other research efforts have focused on studying pathways that block leptin from doing its job, Mazor and colleagues decided to investigate the leptin receptor in the brain itself.
"Our hypothesis was that an enzyme breaking down proteins into amino acids and polypeptides can cleave membrane receptors and lead to dysfunctional activity," Mazor said.
Researchers are calling for a large-scale clinical trial to investigate whether MMP-2 inhibitors might help people lose weight. Those in the early stages of being overweight might be clipping their leptin receptors, but their neural pathways are still HEALTH-BRAIN-EATING intact.
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