Scientists gain new insights into 'obesity gene'

EU-funded scientists have gained new insights into how the ‘obesity gene’, FTO, causes people to gain weight. Writing in the journal Science, they explain that the gene is most active in the
hypothalamus, the part of the brain responsible for controlling hunger and satiety.

Earlier this year, researchers discovered that people with a certain variant of the FTO gene tend to be heavier than other people and have an increased risk of diabetes. Since then scientists
have been hard at work trying to find out how FTO influences our body weight.

EU funding for the research came from the Sixth Framework Programme DIABESITY project, which is investigating the action of genes implicated in obesity with a view to exploiting them as drug
targets.

‘This is the very first glimpse into the possible mechanisms whereby this very common genetic variant might influence a person’s risk of obesity,’ commented Professor Stephen O’Rahilly of the
University of Cambridge.

The researchers found that the FTO gene codes for an enzyme which is able to act on our DNA and modify it. This suggests it may be responsible for turning other genes on and off.

Furthermore, the FTO gene is particularly active in the hypothalamus, the part of our brain which controls hunger levels, and levels of FTO are influenced by feeding and fasting.

‘The finding that FTO is an enzyme with these actions on DNA is very surprising and a lot of work is still needed to work out how its actions influence body weight,’ said Professor O’Rahilly.
‘The finding that FTO may have some involvement in the control of the function of the hypothalamus suggests that, like other obesity genes previously discovered, it may play some role in
influencing how well the brain senses hunger and fullness.’

According to Professor O’Rahilly, the fact that the activity levels of FTO can be altered by small molecules means it could be possible to manipulate it therapeutically to treat obesity.

‘This is an important piece of research,’ said Sara Hiom of Cancer Research UK, which also funded the study. ‘We know that obesity increases people’s risk of developing a range of cancers as
well as other diseases, and the increasing number of people who are overweight will have significant implications for cancer in the future. Unravelling how this gene works is very exciting and
may one day lead to new treatments for obesity.’

One in six white Europeans carries two copies of the obesity-linked variant of FTO. These people are, on average, three kilos heavier and 70% more likely to be obese than people with no copies
of the ‘obesity’ gene. People with just one copy of the ‘obesity’ variant of FTO are 1.6kg heavier and have a 30% increased risk of obesity compared with someone with no copies.

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