Scientists at the Medical Research Council (MRC) have provided convincing proof of the direct connection between the FTO gene and obesity, obtaining the first direct evidence that overactivity of the gene leads to overeating and obesity in mice.

The findings by research team from MRC Harwell and the University of Oxford suggest that the gene could be a promising target for developing anti-obesity drugs that act by turning down the gene's activity.

Chris Church, a Ph.D student from MRC Harwell and first author on the study, said:

"For the first time we have provided convincing proof that the FTO gene causes obesity. The next step is to understand how it does this, for instance whether it increases appetite by influencing our brain or alters messages from our fat stores and other tissues. Once we know how FTO causes obesity we have the potential to look at developing drugs to treat it."

"Genome-wide association studies have done a fantastic job narrowing down the areas in the genome responsible for obesity. They've provided signposts of where to look, but these areas still need pinning down to a precise gene, as we have done here for the first time with FTO. The mouse model has enabled us to achieve this in just a few years, and we hope the same process will now be applied to the other gene areas implicated in obesity, enabling scientists to confirm precisely which other genes can predispose us to become overweight." Earlier genome-wide association studies have flagged the FTO gene as an area of importance for obesity. In this study, the researchers set out determine whether it was differences in the activity of the FTO gene itself that was directly causing the increase in body weight.

The scientists bred mice with extra copies of the FTO gene. These mice were healthy, but ate more and became fatter than normal mice. Female mice with two extra copies of the FTO gene, when fed a standard diet, became 22 per cent heavier than normal female mice after 20 weeks. The difference in weight for male mice was 10 per cent. The researchers also showed that the difference came because mice with FTO overactivity consumed more food. There is no suggestion that weight differences in humans with FTO variants would be as large or necessarily affect the sexes in a similar proportion.

Professor Roger Cox of the Medical Research Council's Mammalian Genetics Unit at Harwell, and one of the leaders of the research, said:

"This gene is novel to obesity research and it is going to be exciting to find out how it works,' says 'We have the mouse models now to address these questions." Almost 1 in 3 people in the UK are overweight or obese, placing them at greater risk of other diseases, such as heart disease, type 2 diabetes and cancer. The MRC funds research which seeks to understand the links between genetics and disease and will pave the way for new drugs to counter the obesity epidemic. The estimated cost of obesity to the NHS is approximately £1 billion a year.

The paper 'Overexpression of Fto leads to increased food intake and results in obesity' by Chris Church and colleagues is published in the journal Nature Genetics on Sunday 14 November 2010. The study was funded by the Wellcome Trust and MRC.

Medical Research Council