There are many obvious causes for obesity — overeating and lack of exercise among them — but there are also some less obvious ones.
After an arduous search, scientists in Britain think they have found a common gene that may explain why some people put on unwanted weight. The gene clearly isn't the entire explanation for the obesity epidemic, but it may provide some clues to solving it.
There is no question that genetics play some kind of role in obesity and the related problem of diabetes, but finding the specific genes has been extremely difficult. So a team led by Andrew Hattersley of the Peninsula Medical School in Exeter, England has tried a new approach: looking directly at DNA samples of overweight and non-overweight people.
The team identified a particular variant of a gene linked to obesity; people with one or two copies of the gene's variant were more likely to be overweight than those who had no copies at all. The results of the study appear in the journal Science.
A New Approach
In the past, Hattersley says, scientists used biology to try to find genes for diabetes and obesity; researchers would look for an enzyme, or protein or other body chemical that was different between overweight and non-overweight individuals. Researchers would then try to find the gene that makes that particular enzyme or protein or chemical.
"It hasn't been a very successful approach," Hattersley says.
Hattersley and his colleagues decided to abandon the old approach and look directly at DNA samples. His team looked at the genes of obese and non-obese people to see if there were any differences between the two populations.
They found that a particular form – or variant – of a gene called FTO was related to weight.
"The people who have two copies of this variant," Hattersley says, "were more likely to be fatter than those who had one copy, [who] in turn, were fatter than those who had no copies."
As Hattersley and his colleagues report, the weight gain was relatively modest. They had to analyze the DNA of nearly 40,000 people to be certain that their gene really was related to gaining weight, and not some statistical fluke.
Joel Hirschhorn of Children's Hospital Boston and the Broad Institute is also in the hunt for obesity genes. He says it is easy to miss something real unless you look for it in a lot of people. He has a Las Vegas analogy that might be useful in understanding this concept.
"If you have a pair of dice," Hirschhorn said, "and they're slightly loaded... you might not notice if you rolled them a few times. But if you rolled them many thousands of times, and you start seeing a few more double sixes than you would expect, you can become very convinced that these are loaded dice."
Hirschhorn says no one thinks this is the whole explanation for why so many people are overweight.
"This is far and away the best evidence that there is for an obesity gene," Hirschhorn says, "but we should be able to find lots of other genes that give us lots of other clues to what causes obesity in people."
Finding a gene is one thing, but figuring out what it does is another. Hattersley says that is what will happen next with FTO. At the moment, no one knows very much about it.
"Because this gene is completely unknown," Hattersley says, "there have only been two scientific papers written about it. In many ways the excitement is what it will teach us in the future."
It may turn out that scientists will find an easy way of blocking it, so that people who have the fat form of the gene can lose weight more easily. Wouldn't that be a lucky roll of the dice?