An international group of scientists have solved the mystery of a genetic flaw which greatly increases the risk of obesity in one in six people.
A version of an obesity gene, called FTO, had been linked to a bigger belly, but the reason why was uncertain.
A study, published in The Journal of Clinical Investigation, showed FTO gene made fatty foods more tempting and altered levels of the hunger hormone, ghrelin.
Obesity experts said drugs targeting ghrelin might reduce weight gain.
There is a strong family link with obesity, and a person’s genetic code is thought to play a major role in the risk of them becoming overweight.
People have two copies of the FTO gene – one from each parent – and each copy comes in a high and a low-risk form. Those with two-high risk copies of the FTO gene are thought to be 70% more likely to become obese than those with low-risk genes.
But no-one knew why.
FTO gene made fatty foods more tempting and altered levels of the hunger hormone, ghrelin
A team, led by researchers at University College London, tested two groups of men. All were a normal weight, but one group had the high-risk FTO genes and the other was low risk.
The first tests looked at levels of the hormone ghrelin either side of a meal in 10 men from each group.
Levels of the hormone, which makes people hungry, did not fall as far in the high-risk patients after the meal. Their ghrelin levels also began to climb more quickly.
In separate tests, a series of brain scans after a meal showed further differences between the two groups. Men with the high-risk genes found pictures of high-fat foods more appealing than the low-risk men.
Dr. Rachel Batterham, the head of the centre for obesity research at University College London, said: “Their brain is set up to be particularly interested in anything to do with high-calorie food.”
She said they were “biologically programmed to eat more”.
Dr. Rachel Batterham said understanding how FTO affected the odds of becoming overweight would help patients.
She said exercise such as cycling was an excellent way to lower ghrelin levels and there was a significant amount of research from pharmaceutical companies working on the hormone.
Dr. Rachel Batterham added: “Also protein meals do lower ghrelin more, so anything that suppresses ghrelin is more likely to be effective in FTO patients.”
The FTO mutations were probably life-saving at one point in human history when piling on the pounds in the summer would help people survive the winter.
A genetic flaw may explain why some people get more ill with flu than others, say scientists.
Published in Nature, the research found that a variant of the IFITM3 gene was much more common in people hospitalized for flu than in the general population.
It controls a malformed protein, which makes cells more susceptible to viral infection.
Experts said those with the flaw could be given the flu jab, like other at-risk groups.
Researchers removed the gene from mice. They found that when they developed flu, their symptoms were much worse than those seen in mice with the gene.
Evidence from genetic databases covering thousands of people showed the flawed version of the gene is present in around one in 400 people.
The scientists, who came from the UK and US, then sequenced the IFITM3 genes of 53 patients who were in hospital with flu.
Three were found to have the variant – a rate of one in 20.
The researchers say these findings now need to be replicated in bigger studies. And they add it is probably only part of the genetic jigsaw that determines a person’s response to flu.
A genetic flaw may explain why some people get more ill with flu than others, say scientists
Professor Paul Kellam of the Wellcome Trust Sanger Institute, who co-led the research, said: “At the moment, if someone is in a more vulnerable group because of co-morbidity [another health problem], they would be offered the flu vaccine.
“This is the idea here.”
But he said having this variant would not make any difference to how people were treated.
Prof. Paul Kellam added: “Our research is important for people who have this variant as we predict their immune defences could be weakened to some virus infections.
“Ultimately as we learn more about the genetics of susceptibility to viruses, then people can take informed precautions, such as vaccination to prevent infection.”
Professor Peter Openshaw, director of the Centre for Respiratory Infection at Imperial College London, said: “This new discovery is the first clue from our detailed study of the devastating effects of flu in hospitalized patients.
“It vindicates our conviction that there is something unusual about these patients.”
Sir Mark Walport, director of the Wellcome Trust, said: “During the recent swine flu pandemic, many people found it remarkable that the same virus could provoke only mild symptoms in most people, while, more rarely, threatening the lives of others.
“This discovery points to a piece of the explanation: genetic variations affect the way in which different people respond to infection.
“This important research adds to a growing scientific understanding that genetic factors affect the course of disease in more than one way. Genetic variations in a virus can increase its virulence, but genetic variations in that virus’s host – us – matter greatly as well.”
