Scientists Uncover the Mechanism of Brain's 'Hunger Switch'

Obesity, drugs, and the MC4 receptor

Genetically inherited mutations in this receptor are believed to be a relatively common cause of severe childhood obesity. While companies are racing to make drugs that target MC4, the limited knowledge on the receptor caused the drugs to have various side effects.

By using cryogenic electron microscopy, the 3D structure of the MC4 receptor was uncovered, giving insight into how it functions. The study revealed setmelanotide (Imcivree), which is a medication for the treatment of obesity, activates the MC4 by hitting the switch that causes us to feel full and does this better than the natural satiety hormone. Approved in November by the U.S. FDA, reported side effects of setmelanotide included depression, suicidal thoughts, spontaneous erections in males, and adverse sexual reactions in females, as well as nausea, diarrhea, and abdominal pain.

"Now that we know the precise molecular details of the switch, we can use this to target it very precisely and design drugs that can avoid some of the side effects that have been encountered with this first drug," said Dr. Moran Shalev-Benami of Weizmann Institute to The Times of Israel.

Through other experiments, the scientists were able to uncover that calcium also helps the natural satiety hormone, much like setmelanotide.

Additionally, hotspots that differentiate MC4 from similar receptors in the same family have been identified, which means, scientists can now design drugs that only bind to MC4, thus having fewer side effects.

While the study is directed towards anti-obesity medications and helping people with genetic conditions that directly affect MC4, it could also have implications for those trying to diet.