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Obesity gene acts on DNA

5 November 2007 

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: ‘this 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.

For more information contact Professor Chris Schofield on +44 (01865) 275625 or email christopher.schofield@chem.ox.ac.uk or contact Professor Frances Ashcroft on +44 (01865) 285810 or email frances.ashcroft@physiol.ox.ac.uk

Alternatively contact the University of Oxford Press Office on +44 (01865) 283877 or email press.office@admin.ox.ac.uk


Notes to Editors

*A report of the research entitled ‘The Obesity-Associated FTO Gene Encodes a 2-Oxoglutarate-Dependent Nucleic Acid Demethylase’ will be published online in Science Express on 8 November 2007.    

*The team was led by Professor Chris Schofield of Oxford University’s Department of Chemistry with Professor Chris Ponting and Professor Frances Ashcroft from Oxford’s Department of Physiology, Anatomy and Genetics and, at the University of Cambridge, by Professor Steve O’Rahilly.

*In the UK it is estimated that 20% of men and 25% of women are obese, and that as many as 30,000 people die prematurely from obesity-related conditions every year.  At the current rate of increase, three-quarters of the UK population could be overweight by 2025. Obesity-related conditions are expensive to treat and cost the NHS at least £500m a year.

  

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