Ghrelin levels normally increase before meals and fall afterward, but researchers found the men with the double FTO variant had much higher ghrelin levels after a meal and felt hungrier after eating than men who had the variation that carries lower obesity risk.
In the next step, the research team used functional MRI to measure how the brain responds to food images and ghrelin levels before and after a meal, using a different group of 24 men.
MRI scans revealed altered brain activity in the double-variant men, both in the appetite-controlling hypothalamus and the brain's "reward" regions, which are known to respond to alcohol and recreational drugs. The altered activity occurred in response to food images and to the ghrelin in their bloodstream.
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."