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November 9, 2007

Researchers Illuminate Obesity Gene’s Mechanism of Action

  • British scientists discovered that a common obesity gene triggers weight gain in some individuals by expressing an enzyme that changes the expression of other genes. 

     Earlier this year a team of British geneticists discovered that variation in a gene called FTO influences people’s risk of becoming obese. About half the U.K. population carries a copy of the variant and has a 30% increased risk of being obese compared to a person with no copies. Additionally, 16% of the U.K. population carries two copies of the variant, which confers a 70% risk. Carriers of the variant also had an increased risk of diabetes.

    In the current study, investigators found that the FTO gene codes for an enzyme can act directly on DNA to modify it. They also found that, in mice, FTO is highly expressed in the hypothalamus, which has important roles in the control of hunger and satiety, and that, in certain parts of the hypothalamus, the levels of FTO are influenced by feeding and fasting.

    “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 also play a role in influencing how well the brain senses hunger and fullness. As the activity of FTO can be altered by small molecules like metabolites, it is possible, in the future, that FTO could be manipulated therapeutically to help treat obesity,” says Stephen O’Rahilly who led the the University of Cambridge’s efforts and is a professor in and head of the department of clinical biochemistry and medicine.

    The research was performed by scientists from the University of Cambridge, Oxford University, and Cancer Research UK. Their findings are reported online in Science Express.