your DNA Making You Obese?
Certain DNA might keep people
hungry, study suggests
Researchers have discovered a potential
genetic explanation for why some people overeat and run a greater risk for obesity.
People who carry two copies of a
variant form of the "FTO" gene are more likely to feel hungry soon
after eating a meal, because they carry higher levels of the hunger-producing hormone ghrelin in their
bloodstream, an international team of scientists found.
What's more, brain scans revealed
this double FTO gene variant changes the way in which the brain reacts to food
and ghrelin. People with the double variant displayed different neural
responses in the brain region known to regulate appetite and the
pleasure/reward center that normally responds to alcohol and recreational drug
About one in every six people
carries two copies of this FTO gene variant. These folks are 70 percent more
likely to become obese than people who carry other versions of FTO gene,
according to background information in the study published July 15 in the Journal
of Clinical Investigation.
"We've known for a while that
variations in the FTO gene are strongly linked with obesity, but until now we
didn't know why," said lead author Dr. Rachel Batterham. "What this
study shows us is that individuals with two copies of the obesity-risk FTO
variant are biologically programmed to eat more."
Evolution may be responsible for the
existence of this double variant in so many people.
"For the majority of the time
that humans have existed food has been scarce. Having this genetic variant
would have conferred a survival advantage," said Batterham, head of
obesity and bariatric services and director of Center for Obesity Research at
University College London Hospitals.
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
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
"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
"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
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."