The genes which protect around four million people in the UK from obesity have been discovered following a major research project.
Scientists at Cambridge University say drugs to keep people slim are now a possibility after they identified the handful of genetic factors that prevent overeating.
Medics have known for several years that genes can influence a person’s weight.
However, the new study is significant because it reveals in granular detail which variants suppress or encourage appetite.
The research team analysed the genetic profiles of more than half a million volunteers from the UK Biobank.
They found that around six per cent of British people with European ancestry have a particular combination which means they are more likely to avoid putting on weight regardless of their lifestyle.
Published in the journal Cell, the study focused on a gene known as MC4R which was previously identified by the same Cambridge scientists to play a role in appetite by controlling a receptor in the brain called melanocortin 4.
People who had certain variants of MC4R which disrupted this receptor tended to gain weight easily, the study found, while those who had a different combination caused the receptor to stay “switched on”, enjoying the opposite effect.
Participants with these variants would eat less, which probably explaining their lower weight.
The team found that people with two copies of these particular variants – one in over 1,000 people in the UK – were on average 2.5 kg lighter than people without the variants and had a 50 per cent lower risk of type 2 diabetes and heart disease.
Professors Sadaf Farooqi, who co-led the project, said: “This study drives home the fact that genetics plays a major role in why some people are obese – and that some people are fortunate enough to have genes that protect them from obesity.
“It doesn’t mean that we can’t influence our weight by watching what we eat, but it does mean the odds are stacked against some people and in favour of others.”
Through laboratory experiments, Professor Farooqi and his colleagues established that MC4R can send signals through a pathway, known as the beta-arrestin pathway, that had not previously been linked to weight regulation.
Genetic variants that sent signals preferentially through this route were the ones driving the association with protection against obesity and its complications and, importantly, were also associated with lower blood pressure.
The insight forms a platform for the development of new drugs which mimic the newly identified pathway.
“Genetic studies of thousands of people and a functional understanding of the mechanisms behind protective genetic variants can really help us inform the development of a new generation of medicines for common diseases like obesity and diabetes that affect millions of people globally,” said Professor Nick Wareham, who also took part in the study.
Almost one in three adults are now estimated to be obese – which is set to rise to 48 per cent in the next three decades.
The figure is more than double the forecast global average of 22 per cent, said the University College London report.
The US the only developed country predicted to fare worse – reaching 55 per cent.
Around 10 per cent of adults in the UK already have type two diabetes, which is closely linked to excess weight.
The data presented at the European Congress on Obesity in Vienna last year suggested this will reach almost 13 per cent by 2045.
Story cited here.
