The pesky gene that could make you 20kg heavier: Leading expert reveals how mutation can leave you a

Every day we choose what meals, snacks and drinks we’d like to tuck into.

But rather than this choice being completely within our control, genes could be dictating what, and how much, we eat.

One in particular, called MC4R, is vital for regulating body weight.

While everyone has two copies of it, some people who have a mutated version find it much harder to resist the urge to eat.

Studies suggest that people who carry the variant weigh nearly 20kg (3st 2lbs) more than their peers.

One gene in particular, called MC4R, is vital for regulating body weight. While everyone has it, some people who have a mutated version find it much harder to resist the urge to eat

Melanocortin-4 receptors (MC4R) have been linked to obesity since the 1990s.

When it works properly, it produces a protein that signals to the brain’s appetite sensors when the body has enough fat stored and, therefore, when it is full, experts say.

However, if one or both copies of this gene are faulty, it can incorrectly flag to the brain that it is lacking in fat stores — fuelling a desire to overeat.

NHS genetic tests for severe early-onset obesity can detect the mutation and some online tests, costing up to £800, claim to spot it as well. 

A 2021 study by researchers at the University of Bristol and the University of Cambridge revealed just how much of an impact this genetic quirk can have.

They looked at the data of 5,724 children born in Bristol between 1990 and 1991.

What is melanocortin-4 receptors (MC4R)?

Melanocortin-4 receptors (MC4R) have been linked to obesity since the 1990s.

Everyone has two copies of the gene.

When it works properly, it produces a protein that signals to the brain’s appetite sensors when the body has enough fat stored and, therefore, when it is full, experts say.

However, if one or both copies of this gene are faulty, it can incorrectly flag to the brain that it is lacking in fat stores — fuelling a desire to overeat.

A Cambridge University study suggests that three in 1,000 people have the mutation.

This group were 17.8kg (39lbs) heavier by age 18, on average, than those who did not have it, according to the findings.

They also had a BMI score that was 4.8 points higher and carried 14.8kg more fat. 

However, studies also show that there are nine mutations to the MC4R gene can help people stay skinny and dodge type 2 diabetes and coronary artery disease. Around six per cent of people are thought to be carrying these. 

Results showed 17 (0.3 per cent) had mutations in one of their copies of MC4R, which caused their brains to sense that they had less body fat than they actually did.

At the age of 18, those with the mutation were 17.8kg (39lbs) heavier, on average, than those who did not have it, according to the findings. 

They also had a BMI score that was 4.8 points higher and carried 14.8kg more fat.

The scientists, who shared their results in the journal Nature Medicine, warned that those who carry the variant risk entering adult life with a ‘substantial burden’ of excess fat. 

They suggested that the so-called obesity mutation may affect up to 200,000 Brits and 1million Americans.

Professor Giles Yeo, a geneticist who studies obesity at the University of Cambridge and co-author of that study, discussed the research this week at a Royal Society conference.

He said: ‘You can’t magic energy into your body and you certainly can’t magic the energy away. 

‘The only way you’re going to be able to gain weight is to eat more than you burn, and ergo, the only way to lose weight is to burn more than you eat. Clearly your body weight is a function of physics — but that is the how.

‘Where the biological variation lies, where the interesting things that we can do and think about lies, comes in the why — why do people behave so very differently around food?’

He said genetic modifiers, such as MC4R mutations, run through the entire process of food intake, which is controlled by the brain.

Discussing whether obesity is a choice, he said: ‘Am I giving anyone any excuse? Hopefully the answer is no. 

‘But I think you’ve got to consider your genes like a hand of cards — you get bad hands.

‘And the only people you can blame are your parents because that’s where it’s come from. But you can win with a bad hand, it’s just more difficult.’

Professor Yeo said: ‘We do not lose or gain weight overnight. We just don’t. Any given meal, no matter how big, is not going to perceptibly change your body weight. Your body weight is a function of thousands of different feeding events over the past few years. 

‘But imagine if because of your genetic hand of cards, you’re a few percentage points less likely to say no [to overeating] — five per cent. 

‘Five per cent over thousands of eating events is hundreds of thousands of calories.’

He added: ‘Until we in society understand that for people with obesity, it’s always going to be more difficult, they’re fighting their biology, we’re never going to be able to fix the problem.’ 

A separate study suggested that mutations in the MC4R gene fuels unhealthy food choices. 

Researchers at Cambridge recruited people who had a healthy weight and were obese, with some of the latter having MC4R mutations.

They were offered three bowls of chicken korma and three bowls of Eton mess — each of which either had a low, medium or high fat or sugar content — and told to pick the option they liked the most and eat as much as they wanted.

Those with the mutation ate almost twice the amount of high-fat curry than their slimmer counterparts and 65 per cent more than others who were obese but did not have the genetic quirk. However, they ate significantly less of all Eton mess variations compared to the other two groups.

The team concluded that those with the gene prefer high-fat food without realising it, a habit which contributes to their weight problem. 

They suggested that the MC4R mutation may be a way of the body protecting against starvation by encouraging the consumption of high-fat food.

Research has also suggested that MC4R is involved in the development of obesity-related health conditions, such as type 2 diabetes and high blood pressure.

Scientists believe this is down to the molecule having a role in maintaining healthy insulin levels and blood pressure.

Yet, being obese can lead to both conditions and may be a simpler explanation. 

However, studies also show that there are nine mutations to the MC4R gene can help people stay skinny and dodge type 2 diabetes and coronary artery disease. Around six per cent of people are thought to be carrying these.

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