Science, has revealed how the master switch for hunger in the brain, the melanocortin receptor 4 (MC4), works.
The research team, including scientists from the Weizmann Institute of Science, Queen Mary University of London and the Hebrew University of Jerusalem, also clarified how this switch is activated by setmelanotide (Imcivree), a drug recently approved for the treatment of severe obesity caused by certain genetic changes.
The findings shed new light on the way hunger is regulated and could help to develop improved anti-obesity medications.
Unexpected finding
The study uncovered the 3D structure of the MC4 receptor, through the use of recent advances in cryogenic electron microscopy. The 3D structure revealed that setmelanotide activates the MC4 receptor by entering its binding pocket –directly hitting the molecular switch that triggers us to feel full- even more potently than the natural satiety hormone. It also turned out that the drug has a surprising helper: an ion of calcium that enters the pocket, enhancing the drug's binding to the receptor. In biochemical and computational experiments, the scientists found that similarly to the drug, calcium also assists the natural satiety hormone.