Scientists have found that a gene linked with obesity triggers weight gain by failing to dampen hunger after meals, paving way for new treatments to tackle the condition.
The study led by scientists at University College London, the Medical Research Council (MRC) and King's College London Institute of Psychiatry shows that people with the obesity-risk FTO variant have higher circulating levels of the 'hunger hormone', ghrelin, in their blood.
This means they start to feel hungry again soon after eating a meal, researchers said.
Real-time brain imaging also showed that the FTO gene variation changes the way the brain responds to ghrelin, and to images of food, in the regions linked with the control of eating and reward.
Together these findings explain for the first time why people with the obesity-risk variant of the FTO gene eat more and prefer higher calorie foods compared with those with the low-risk version, even before they become overweight.
Scientists led by Dr Rachel Batterham recruited 359 healthy male volunteers to examine the 'real life' effects of the FTO variation in humans.
They studied two groups of participants - those with two copies of the high obesity-risk FTO variant (AA group) and those with the low obesity-risk version (TT group).
A group of 20 participants (10 AA and 10 TT) were asked to rate their hunger before and after a standard meal, while blood samples were taken to test levels of ghrelin - a hormone released by cells in the stomach that stimulates appetite.
Normally ghrelin levels rise before meals and fall after eating, but in the study men with the AA variation had much higher circulating ghrelin levels and felt hungrier after the meal than the TT group.
This suggests that the obesity-risk variant (AA) group do not suppress ghrelin in a normal way after a meal.
The researchers then used functional magnetic resonance imaging (fMRI) in a group of 24 participants to measure how brain responds to pictures of high-calorie and low-calorie food images, and non-food items, before and after a meal.
Individuals with the obesity-risk FTO variant rated pictures of high-calorie foods as more appealing after a meal than the low-risk group.
In addition, the results revealed that the brains of the two groups responded differently to food images (before and after a meal) and to circulating levels of ghrelin.
Finally, the scientists looked at mouse and human cells to uncover what causes increased ghrelin production at a molecular level. They over-expressed the FTO gene and found that this altered the chemical make-up of ghrelin mRNA (the template for the ghrelin protein) leading to higher levels of ghrelin itself.
Blood cells taken from the obesity-risk group also had higher levels of FTO gene expression and more ghrelin mRNA than the low-risk group.
The study was published in the Journal of Clinical Investigation.
