For some people, the quest to lose weight feels like a constant struggle.
Now, scientists have revealed that a newly discovered ‘fat gene’ could be to blame.
Experts from the University of Cambridge say that a mutation to a gene called DENND1B reduces the ability for some people to resist food.
The same genetic mutation is also found in Labrador retrievers, and could explain why this breed is particularly prone to obesity.
According to the experts, the mutation may also be linked to the development of childhood asthma and immune disorders.
‘DENND1B acts as a dimmer switch to change the brain’s response to food,’ lead study author Dr Eleanor Raffan told MailOnline.
‘In people, the effect of DENND1B is very subtle – it makes about 0.01 of a BMI point’s difference. This is a small effect size and just one of over 1,000 discovered genetic variations across the genome which can increase or decrease a person’s tendency to weight gain.
‘But these variations add up such that their net effect makes a “genetic risk burden” making a person prone to obesity, or relatively resistant to developing it.’
Obesity means you carry way too much body fat – but it isn’t just caused by how much you eat, according to researchers. As many as 400 genes have been shown to affect body weight in one way or another (file photo)
In humans, obesity is measured using the body mass index (BMI).
But in dogs, it is measured by the body condition score (BCS).
The BCS assesses dogs on a scale of one to nine, from ’emaciation’ with no visible body fat to ‘excessive’ body fat with no discernible waist (severely overweight).
For this study, the experts recruited 241 pet Labrador retrievers of both sexes, with a BCS ranging from three (slightly underweight) to nine (severely overweight).
Dogs are a good model of human obesity, partly because they develop obesity due to similar environmental influences as people, such as limited exercise and eating too much.
The scientists assessed each dog’s ‘greediness’, by seeing how much it pestered their owner for food and whether it was a fussy eater.
Next, the researchers took saliva samples from the dogs and scanned markers across the complete sets of DNA to find genetic variations.
They identified multiple genes linked to obesity in dogs, but the team identified a rare and harmful DENND1B mutation which had the strongest genetic link with canine obesity, influencing both BCS and body weight.
Under the BMI system, a score of 18.5 to 25 is healthy. A score of 25 to 29 counts as overweight, and 30-plus means a person is obese, the stage at which chances of illness rocket
Researchers performed a canine genome-wide association study for body condition score, a measure of obesity, in 241 Labrador retrievers
The genetic variant was found to directly affect the so-called ‘leptin melanocortin pathway’ in the brain, responsible for regulating hunger.
Dogs with a genetic mutation to the DENND1B gene had around eight per cent more body fat than those without it – and larger than in humans.
The researchers stress that no single gene determined whether the dogs were prone to obesity, but the DENND1B mutation has the strongest link.
It was somewhat unsurprising then that the dogs at higher genetic risk of obesity showed signs of having higher appetite.
‘We also identified a single [human] patient who had very severe obesity early in life and who had two copies of a mutation in DENND1B,’ Dr Raffan added.
The new study, published in the journal Science, adds to a body of evidence that obesity is influenced by biological as well as environmental factors.
However, the prevalence of the gene variant does not mean humans and dogs are destined to be obese.
The study found owners who strictly controlled their dogs’ diet and exercise managed to prevent them from becoming obese even if they had the high genetic risk.
DENND1B is a gene which acts as the blueprint to build a protein. DENND1B acts as a dimmer switch to change the brain’s response to food – but a DENND1B mutation makes humans and Labradors more likely to become obese
Being overweight or obese results in about 2.8 million deaths a year, according to the World Health Organisation (WHO). Pictured, an obese woman
So even those who are genetically predisposed for obesity can effectively fight the condition by eating in moderation and exercising frequently.
In absence of exercise and a good diet, the affect the mutation has on our ability to resist food may be particularly lethal.
‘If you have a high genetic risk of obesity, then when there’s lots of food available you’re prone to overeating and gaining weight unless you put a huge effort into not doing so,’ said Dr Raffan.
Past research has already demonstrated significant links between DENND1B variants and body mass index (BMI) in humans, the team add.
Unfortunately, genes associated with obesity are not obvious targets for weight-loss drugs, according to study co-author Alyce McClellan.
‘These genes control other key biological processes in the body that should not be interfered with,’ she said.
‘But the results emphasise the importance of fundamental brain pathways in controlling appetite and body weight.’
