'Convincing proof' of obesity link to Fto gene

Scientists have found a direct link between the 'fat mass and obesity associated' (Fto) gene and increased weight. Research published in 2007 uncovered an association between variations in the Fto gene and increased body weight in humans.

The Fto gene is not the only gene associated with increased predisposition to obesity, but it is the most significant genetic factor so far identified. Seventeen percent of Europeans have two copies of a common Fto variant. On average, this population is 3kg heavier and has a 1.3 times greater likelihood of being obese.

Until now it was not known whether the link between obesity and Fto was direct or caused by some other factor. The team at MRC Harwell in Oxford predicted that increased expression of Fto may be causing obesity since the Fto variant in humans has been linked to increased expression of the gene in some tissues. To test this, they bred mice with extra copies of the Fto gene.

The team found that the test mice became fatter than the normal mice. What's more, the increase in weight gain was greater the more copies of the gene the test mice had. The researchers attributed the weight gain to an increase in food intake rather than differences in the way the mice metabolise their food.

Chris Church, a PhD student and first author on the paper, said the results were 'convincing proof' that the Fto genetic variants contributed directly to obesity. One of the senior authors of the study, Professor Frances Ashcroft of Oxford University said: 'This work makes us confident that Fto is an important gene that contributes to obesity. Too much activity of this gene can lead to putting on weight by overeating'.

'We see an increase in actual fat mass (in the laboratory mice), which demonstrates that this gene is regulating body weight and regulating it by appetite - the mice eat more and put on more weight as a result,' she said. Professor Ashcroft added that the development of drugs that turn down the activity of the Fto gene as anti-obesity pills is an 'enticing prospect', although a long way off yet.

This present study shows a direct link between Fto and increased weight but does not tell us how Fto works. The team at Oxford think it may involve leptin, a hormone released from fat that affects appetite. Professor Roger Cox, who led the study said: 'This gene is novel to obesity research and it is going to be exciting to find out how it works. We have the mouse models now to address these questions'. The team published their findings in Nature Genetics.