09 Nov 07

Obesity is a rapidly growing problem worldwide

British scientists have made a second breakthrough in under a year in understanding why some people are more liable to gain weight than others.

The Oxford University team, led by Professor Chris Schofield, has been studying FTO, a gene that earlier this year was linked to obesity. In a report of their research, published online this week in Science, the scientists show that the protein corresponding to the FTO is an enzyme, or biological catalyst, that modifies DNA.

Previously, researchers discovered that one variant of the FTO gene causes an average increase in weight of 3kg. However, they were unable to determine what the gene does and why the variant leads to weight gain.

In the new study the team found that, remarkably, the FTO protein resembles enzymes that produce the penicillin antibiotics in bacteria and others that enable humans to sense and respond to changes in oxygen levels – for instance at high altitude. FTO is most closely related to the AlkB family of enzymes that in bacteria repair DNA damaged by chemicals.

The team of Oxford, Cambridge and London scientists went on to show that purified FTO can carry out this repair role and that the FTO protein is targeted to the cell nucleus as expected for a protein that modifies DNA.

Oxford researcher Professor Chris Ponting, one of the key scientists involved, commented: Tthis is an astonishing finding. We never expected this first ‘obesity gene’ to have such a direct effect on DNA’. The Cambridge group led by Professor Steve O’Rahilly discovered that the FTO gene is turned on in regions of the brain concerned with appetite regulation and that FTO levels decrease following fasting.

Professor Frances Ashcroft, a member of the Oxford team, said: ‘Obesity is a rapidly growing problem worldwide that significantly enhances the risk of diabetes, cardiac disease, high blood pressure and cancer.’

This breakthrough provides new leads for investigations into how chemical changes to our DNA cause an increase in fat mass and will ultimately help in the development of new drugs to treat obesity.