Around four million people in the UK carry genetic variants that protect them from obesity, type 2 diabetes and heart disease, suggests new research from the University of Cambridge. The team say the discovery could lead to the development of new drugs that help people lose weight.
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
Sadaf Farooqi
Scientists have known for several years that genes can influence a person’s weight. One of the genes that is known to play a key role in regulating weight is MC4R, which codes for the melanocortin 4 receptor. This receptor acts like a switch in the brain to suppress appetite. People who have genetic variants that disrupt this receptor gain weight easily.
Now, in a study published today in the journal Cell, researchers have shown that other genetic variants in the MC4R gene that increase the activity of this brain receptor can protect people from becoming overweight, a finding that could lead to the development of new medicines that ‘copy’ the protective effect of these genetic variants to achieve or maintain weight-loss.
A team led by Professors Sadaf Farooqi and Nick Wareham and Dr Claudia Langenberg at the Wellcome Trust-MRC Institute of Metabolic Science in Cambridge looked at the MC4R gene in half a million volunteers from the UK population who have taken part in the UK Biobank study, finding 61 distinct naturally-occurring genetic variants. While some of these genetic variants predisposed people to become obese, other variants provided protection against obesity and some of its major complications, such as type 2 diabetes and heart disease.
To investigate the reasons for this mystery, Professor Farooqi’s team, who previously showed that MC4R works in the brain as a ‘switch’ to tell us to stop eating after a meal, studied the function of these genetic variants in a number of laboratory experiments. They found that MC4R gene variants linked to higher obesity risk stopped the gene from working, whereas variants that offered protection against obesity kept the gene ‘switched on’.
Around six per cent of study participants carried genetic variants that caused the receptor to remain ‘switched on’. People with these variants would eat less, which could explain their lower weight. People with two copies of these particular variants (1 in over 1,000 people) were on average 2.5 kg lighter than people without the variants and had a 50% lower risk of type 2 diabetes and heart disease.
The discovery adds to recent work by the team which showed that some slim people have a genetic advantage when it comes to maintaining their weight.
“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,” says Professor Farooqi of the University of Cambridge Metabolic Research Laboratories.
The work was funded by the MRC and Wellcome, with support from the NIHR Cambridge Biomedical Research Centre.
To read the full article please visit the University of Cambridge Website