Scientists have discovered a ‘switch’ in the brain that controls appetite which explains why some individuals find it hard to stop eating – even when they are full.
Known as MC4 (melanocortin receptor 4), it should be mostly activated or ‘on’, but in some, it is mutated and always shut down. They pile on the pounds.
Lead author Dr. Moran Shalev-Benami, of the Weizmann Institute of Science, London, said: “Our findings can help develop improved and safer anti-obesity drugs.
- Scientists in Fear of This New Predator From Red Sea Eating Native Species in Mediterranean
- Does This Mean We Stopped Being Animal and Started Being Human Due to ‘Copy Paste’ Errors?
- The One Lifestyle Choice That Could Reduce Your Heart Disease Risk By More Than 22%
- Aging: This Is What Happens Inside Your Body Right After Exercise
- Immune-Boosting Drink that Mimics Fasting to Reduce Fat – Scientists ‘Were Surprised’ By New Findings
“They will target MC4R with greater precision.”
A new medication that triggers the gene was approved by the US Federal Drug Administration in November.
Setmelanotide is being given to children who are genetically prone to severe obesity.
The study in Science sheds fresh light on its mechanism – and is a potential ‘game changer’ in the war on obesity.
The MC4R gene lies in a brain region called the hypothalamus. Normally, it should send out commands that cause us to feel full. Our default state is satiety.
When energy levels drop, a ‘time to eat’ hormone turns it off – and we become hungry.
Afterwards, a second ‘I’m full’ hormone is released – and turns the gene back on.
Variants that permanently turn MC4 off cause people to feel constantly hungry. This makes the ‘master switch’ a prime target for medication, such as Setmelanotide.
Switching it on can stop hunger while bypassing all other energy-related signals, but it was not known how it works – until now.
The project was based on a severely obese family of eight in Israel plagued by persistent hunger.
Most had a BMI (body mass index) of over 70, triple the norm.
Their devastating condition was traced to an MC4R mutation that ran in the family.
Powerful microscopes determined its 3D structure in extraordinary detail – down to nucleus level.
Images revealed Setmelanotide activates the gene by entering its ‘binding pocket.’
It directly hits the molecular switch that signals satiety – even more potently than the natural hormone.
The drug also has a surprising helper – an ion of calcium that boosts contact. Further experiments showed it assists in a similar way.
Coauthor Dr. Peter McCormick, of Queen Mary University of London, explained:
“Calcium helped the satiety hormone activate the MC4 receptor while interfering with the hunger hormone and reducing its activity.”
Dr. Shalev-Benami described the phenomenon as “truly unexpected.”
He said:
“Apparently, the satiety signal can successfully compete with the hunger signal because it benefits from the assistance of calcium, which helps the brain restore the ‘I’m full’ sensation after we eat.”
The groundbreaking analysis also revealed the drug’s entry causes structural changes in the gene.
They appear to initiate the signals within the neurons that lead to the sensation of fullness.
It shows mutations interfere with them – leading to never-ending hunger and ultimately obesity.
What is more, the study identified hotspots that crucially distinguish MC4 from similar receptors in the same family.
Added Dr Shalev-Benami:
“This should make it possible to design drugs that will bind only to MC4, avoiding side effects that may be caused by interactions with other receptors.”
Setmelanotide, sold under the brand name Imcivree, leads to weight loss by altering eating behavior.
- Scientists in Fear of This New Predator From Red Sea Eating Native Species in Mediterranean
- Does This Mean We Stopped Being Animal and Started Being Human Due to ‘Copy Paste’ Errors?
- The One Lifestyle Choice That Could Reduce Your Heart Disease Risk By More Than 22%
- Aging: This Is What Happens Inside Your Body Right After Exercise
- Immune-Boosting Drink that Mimics Fasting to Reduce Fat – Scientists ‘Were Surprised’ By New Findings
The latest findings open the door to drugs that treat or cure the underlying genetic problem.