A study by Israeli researchers from the Weizmann Institute of Science, the Queen Mary University of London, and the Hebrew University of Jerusalem, may pave the way for developing drugs that turn off the hunger switch in the brain to inhibit appetite with minimal side effects.
This will hopefully solve the urge to eat even when not hungry that is experienced by many people. Typically, this can be solved through lifestyle changes or being on a diet, but there are cases when medical attention is needed. If not treated, constant hunger could lead to severe obesity.
Researchers identified the melanocortin 4 receptor (MC4 receptor) in the brain that controls the urge to eat, which gives its nickname: the "hunger switch". The MC4 receptor can be found in the hypothalamus where clusters of neurons compute the body's energy balance by processing metabolic-related signals, Weizmann Wonder Wander reported.
The study, entitled "A 3D structure reveals how a unique molecular switch in our brain causes us to feel full - and may help develop improved anti-obesity drugs" published in the journal Science on April 15, sheds new light on the mechanism of hunger and may help develop anti-obesity drugs.
Genetic Mutations Causing Obesity
According to the study's news release, the MC4 receptor is the prime target of anti-obesity drugs, like the setmelanotide, because it is the hunger switch while also bypassing all other energy-related signals. Until now, researchers are still baffled about how this receptor works.
But a genetically inherited malfunction on the MC4 receptor is believed to be the main cause of obesity that is triggered by one genetic mutation that affects 5% of early childhood obesity.
Researchers said that their research could bring about easy manipulation of the receptor among people who inherited that genetic mutation, The Times of Israel reported.
They used a 3D model of the MC4 receptor to give them insights into how the receptor functions. Dr. Moran Shalev-Benami of Weizmann Institute said that they have shown in their study what the receptor looks like and outlined its molecular details.
"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 Shalev-Benami.
Developing New Anti-Obesity Drugs
Interesting Engineering reported that the researchers used cryogenic electron microscopy to create the 3D model of the MC4 receptor.
The study identified setmelanotide (Imcivree), an anti-obesity medication, as a drug that activated the receptor by hitting the switch that signals the brain that the person is full. Researchers noted that it is even better than the natural satiety hormone.
The drug was approved by the FDA last November, with reported side effects of depression suicidal thoughts spontaneous erections in men, and adverse sexual reactions in women. Other side effects also include nausea, diarrhea, and abdominal pains.
Moreover, researchers said that they also found calcium in the MC4 receptor that helps the natural satiety hormone. They also identified different structures MC4 has compared to similar receptors that could help scientists in developing new anti-obesity drugs.
Although their study primarily directed towards developing drugs against obesity, researchers pointed out this also has implications for those who are on a diet.
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