By Kathleen Doheny
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Reviewed by Michael W. Smith, MD
Aug. 1, 2013 -- For people who often feel hungry right after eating, a recent finding about genetics and obesity was, if not welcome news, at least thought-provoking.
People who have two copies of a modified form (or variant) of a certain gene are much more likely to feel hungry after eating a meal, says researcher Rachel Batterham, MD, PhD, of the University College London.
One in six people has two copies of the modified "fat mass and obesity associated" (FTO) gene. That could help explain some obesity. People with this gene have high levels of the hormone ghrelin, which increases hunger.
Batterham and a U.S. expert in genetics and obesity talked about the finding and what it might mean.
Batterham is head of the University College London Centre for Obesity Research and head of Obesity and Bariatric Services at the UCL Hospital. Her study, published July 15 in the Journal of Clinical Investigation, was funded by the Rosetrees Trust and others.
Lu Qi, MD, PhD, is an assistant professor of nutrition at the Harvard School of Public Health.
Q: Can you put this new discovery in perspective with other obesity and genetics findings, since many genes have been linked with body mass index and obesity?
The effect of FTO on obesity, so far, is that it's the most common "genetic contributor to overweight and obesity, and is estimated to affect 1 billion people worldwide," Batterham says.
This is one piece of the puzzle, she says, but possibly a key piece.
Qi agrees. But he cautions that scientists must test many more people to confirm Batterham's results.
Q: At this point, how big of a role might genes play in obesity?
"From previous studies, it is estimated that 40% to 70% of a person's BMI is inherited," Batterham says, but it's complex and not as simple as just giving a percent.
Overall, the role of any single gene [in obesity] is not big, Qi says. However, if all the obesity-related genes are considered, "the effect would be sizable."
Q: Is it possible to be tested for the FTO variant?
Several companies already offer direct-to-customer testing for variants, including FTO, Batterham says. But she wants to study whether knowing that you have the FTO variant would help people make better lifestyle choices.
Q: If you have two copies of the FTO variant, what can you do to avoid obesity?
More research is needed, Batterham says, but she cited studies showing that aerobic exercise and a high-protein diet may help such people. Results of the research have been mixed, she says.
Behavioral therapy might help people who have the double FTO variant avoid temptation, she says.
Q: Could the new findings, as well as other findings, lead to a treatment?
Possibly, Batterham says. She's now looking at lifestyle factors that control ghrelin and also exploring whether lowering ghrelin levels with drugs might help.
Q: Can you give some background on FTO?
"Since 2007, it has been known that people who carry two copies of the obesity-risk variant form of the FTO gene are 70% more likely to be overweight or obese," Batterham says. These people also ate more calories and preferred high-calorie foods, according to research. But no one knew why.
Batterham's team studied 20 men. Half of them had two copies of the FTO variant. The other 10 had a version linked with lower obesity risk. The men rated their hunger before and after eating and had their ghrelin levels measured. The researchers also did brain scans to compare how the brain responds to food images and ghrelin levels between the two groups.
Q: What did you find?
Healthy-weight people with two [modified FTO] copies "fail to suppress their hunger appropriately after eating, so they feel more hungry," Batterham says. After a meal, she says, they have higher levels of ghrelin.
"Their brains respond differently to pictures of food in both the fasted and fed states in key brain regions known to regulate appetite, reward, and motivated behavior," she says. Key regions of the brain that control eating behavior respond to the ghrelin circulating. People with two copies of the FTO variant find high-calorie food images more appealing after a meal than those with the low-risk variant.
Q: What would you tell people with these genetic variants so they don't get discouraged or feel doomed to obesity?
''There is some evidence that telling people that they are at risk and will find it harder to control their weight leads to increased motivation to exercise," Batterham says. Dispensing simple advice, such as ''don't even look at the dessert menu,'' may also help.
"We have shown [in other research] that dietary factors and lifestyle may modify the genetic effects," Qi says. Among the helpful measures are cutting back on sugary drinks and TV-watching time.
SOURCES: Rachel Batterham, MD, PhD, head of the University College London Centre for Obesity Research; head of Obesity and Bariatric Services, UCL Hospital.Karra, E. Journal of Clinical Investigation, July 15, 2013.Lu Qi, MD, PhD, assistant professor of nutrition, Harvard School of Public Health, Boston.
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