NUS team's drug finding could help in obesity

PHOTO: NUS team's drug finding could help in obesity

If you cannot resist fatty food and get hungry soon after a meal, scientists in Singapore may have found a way to help you.

They have discovered several potential drugs which target a genetic variation that greatly increases the risk of obesity in about one in six people.

There are two copies of the gene, called FTO, in each person, but some variations of the gene have been found to make people 70 per cent more likely to become obese.

The scientists said previous research showed the FTO variations' link to obesity exists across age, gender and ethnicity, including the Chinese, Malay and Indian populations in Singapore.

But their FTO research could pave the way for new anti-obesity drugs and treatment that target the disease genetically. This could potentially help people who have had little success in battling the bulge, even with more exercise and healthy eating habits.

The National University of Singapore (NUS) team, led by assistant professor Esther Woon from the Department of Pharmacy, worked with scientists from the Agency for Science, Technology and Research and Nanyang Technological University.

Describing obesity as a widely misunderstood disease, Assistant Prof Woon said: "We frequently hear comments like, 'oh, why don't fat people just exercise more and eat less', but most people fail to appreciate that our body weight is not a personal choice.

"It is very much biologically determined, with strong genetic influences that programme a person's size and appetite."

British scientists had found that people with the FTO variations appeared to be wired to find high-fat foods more appealing.

After those people finished a meal, their levels of ghrelin, which increases hunger, fell less and then climbed more quickly compared with other people who do not have the genetic variations.

The FTO variants have also been linked to higher body mass index in people.

The Singapore scientists experimented with about 30 molecules to find combinations that bind to and inhibit the FTO proteins regulated by the gene.

A drug discovery method, called dynamic combinatorial mass-spectrometry, was used to mix and match the molecules in different ways with the protein, until the most stable and potent combinations were identified.

The scientists then modified the top three combinations to further improve them, such that the inhibitors target only the FTO proteins and not any others.

The research was funded by the National Medical Research Council, and was published online recently in the journal Chemical Science.

The FTO inhibitors have been patented.

The team is working with other NUS scientists in the Yong Loo Lin School of Medicine and the Food Science and Technology Programme to study the inhibitors' effectiveness on other metabolic diseases such as diabetes.

"There is also still a lot to learn about the actual mechanistic link between FTO and obesity. The challenge now is to uncover the mystery through the use of these selective FTO inhibitors," said Assistant Prof Woon.

This article was first published on November 11, 2014.
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