Maybe your genes are driving you to hunt down that last bit of cake (Image: Anouk de Maar/Getty)

If you can’t resist that extra portion of dessert, maybe it is time to stop bemoaning your lack of willpower and blame your genes instead.

Six years after a gene called FTO was linked with obesity, researchers have shown that it probably makes people plumper by failing to dampen their hunger following meals, and by increasing the allure of mouth-watering, high-calorie foods.

In the same way that people can inherit several different variants of an eye-colour gene, people can inherit two different versions of the FTO gene.


People with two copies of one of those variants – “AA” – are 70 per cent more likely to develop obesity than those who inherit two versions of the other type – “TT”. Even having one version of this obesity-related variant – as half of all white Europeans do – raises the risk by 30 per cent, making FTO the gene most strongly linked with obesity.

But until now, no-one knew why. To investigate, Rachel Batterham of University College London and her colleagues fed identical meals to 10 men with two copies of the obesity-linked variant, and 10 men with two copies of the other type. Afterwards the men were asked to rate how hungry they were on a 10-point scale.

Feed me till I want no more

The men with two copies of the obesity variant ranked themselves 20 to 25 per cent hungrier over the next two hours than the non-carriers did. The concentration in their blood of ghrelin, the only hormone known to stimulate appetite, was also elevated by the same amount.

“People with the gene variant don’t suppress ghrelin properly after a meal, so they remain hungry,” says Batterham. “You become a slave to that extra ghrelin.”

But that’s not all. Further experiments by the team on a different set of 24 men revealed that carriers of the FTO gene are more attracted by the prospect of rich food.

When the volunteers were asked to rate the attractiveness of images of different types of food, having already eaten a meal, carriers rated the most calorie-laden foods as 50 per cent more appealing than non-carriers did. Food that wasn’t particularly rich was found to be equally appealing to both groups.

fMRI scans of the men’s brains as they viewed the images showed that the same regions – such as the nucleus accumbens and the hypothalamus – became active in the carriers as in addicts’ brains when they were asked to think about having their next drink or scoring their next hit. This had previously been seen in people who were given injections of ghrelin.

Empowering knowledge

There are ways of limiting the effects of having the obesity-related FTO gene. Exercise and eating a protein-rich diet both suppress ghrelin, and drugs are being developed to suppress the hormone or the enzyme that makes it.

Knowing they have the obesity-linked FTO gene seems to motivate carriers to behave more healthily, so Batterham suggests that screening could help make people change their lifestyles. “It’s empowering rather than giving them an excuse to overeat,” she says.

“Slowly we are discovering the factors which make us overweight and this study, encompassing not only demonstration of a higher hunger hormone, ghrelin, but also changes in the brain associated with ghrelin’s action, is an important step forward,” says Steve Bloom of Imperial College London.

Andrew Hattersley of the University of Exeter, UK, who was part of the team that discovered the FTO obesity variant, says the new work is exciting. But he says that “further replication studies are needed to make sure the effect is entirely through ghrelin”.

People with two copies of the obesity-linked version of the FTO gene carry just 3 kilograms more fat than people with two copies of the other version on average, so it’s unlikely that this is the end of the story.

Journal reference: Journal of Clinical Investigation, DOI: 10.1172/JCI44403