Could a Gene Help Make You Obese?
Certain DNA might keep people hungry, study suggests
Further, men with the double FTO variant rated images of high-calorie foods more appealing after a meal that people with the low-risk variant.
"Not only do these people have higher ghrelin levels and therefore feel hungrier, their brains respond differently to ghrelin and to pictures of food -- it's a double hit," Batterham said.
The doctors then took their research one final step further, using mouse and human cells to figure out what causes increased levels of ghrelin in men with the double FTO variant.
They found that increased expression of FTO gene "unlocks" the genetic template used to create ghrelin, leading to increased production of the hunger hormone.
The study provides "an important contribution to understanding the mechanistic process of how the FTO gene affects hunger and obesity," said Emmanuel Pothos, an associate professor in the department of molecular physiology and pharmacology at Tufts University School of Medicine, in Boston. He was not involved with the study.
However, he noted that the FTO gene alone cannot explain the obesity epidemic. Other studies have found that people with the high-obesity-risk FTO variant weigh on average only 6.5 extra pounds more than people without the variant.
"There certainly are other factors here that are important that we don't know about," Pothos said. "The FTO gene has an important role here, but it's not the only factor."
The possibility exists that other hormonal and neural pathways related to obesity are unlocked through the same mechanism that causes increased ghrelin production, said Ruth Loos, director of the genetics of obesity and related metabolic traits program at the Icahn School of Medicine at Mount Sinai, in New York City.
"It's a very complex interaction they describe. It's a very nice story. It all fits nicely together, and it provides the first insights into how FTO might contribute to obesity," Loos said. "But more research is required."
Study author Batterham said this in no way should convince people with this genetic variant that they are helpless against obesity.
"At a therapeutic level, this arms us with some important new insights to help in the fight against the obesity pandemic," she said. "For example, we know that ghrelin can be reduced by exercise like running and cycling, or by eating a high-protein diet. There are also some drugs in the pipeline that suppress ghrelin, which might be particularly effective if they are targeted to patients with the obesity-risk variant of the FTO gene."