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Interviewee: Rob Waterland, Baylor College of Medicine
Obesity in the Womb
By Heather Mayer
With the obesity epidemic in full force, researchers have been puzzled and concerned at the sheer pace of its spread. "This is puzzling because a lot of people have focused on genetics for so many years," says Rob Waterland, assistant professor of pediatrics at the USDA Children’s Nutrition Research Center at Baylor College of Medicine. "But obviously, the genetic background hasn’t changed dramatically enough in such a short period of time to explain this increase in the prevalence of obesity."
So Waterland and others have looked for another explanation of how obesity is inherited. They’ve suggested that obesity isn’t merely genetic — it is somehow triggered in the womb during development. Now Waterland and his team’s latest study in mice shows that mom’s obesity not only generates obesity in her offspring but also magnifies it.
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“They were actually fatter than their mothers, so we saw a population shift in the distribution of body weight,” Waterland explains. “We saw a shift in this distribution toward heavier and heavier body weight with each generation.”
The researchers were able to show that these inherited changes are not due to genetic changes. Instead, they attributed to them to epigenetic changes, which control the way genes are expressed during development. If human obesity through the generations is triggered by epigenetics, it’s possible that a mother’s obesity before and during her pregnancy can permanently affect the development of her baby’s weight regulatory mechanisms.
“So-called epigenetic mechanisms could be playing an important role in determining your body weight regulation throughout your life," Waterland says.
Fat Mice Produce Fatter Mice
The question the researchers set out to answer had to do with a fetus’s environment and how that might affect its weight.
“People have postulated that if an obese woman becomes pregnant, there may be something unique about the intrauterine environment that her fetus is exposed to that may actually change the development of her fetus, and actually alter the development of body weight regulation mechanisms that will then cause her child to be more prone to obesity,” explains Waterland.
Waterland and his team followed three generations of genetically identical mice that had a tendency to overeat and become obese. Because all of the mice were genetically identical , getting fat couldn’t be due to changes in their DNA.
“This was a non-genetic transmission of obesity across generations,” Waterland says.
Obesity Reversal Supplement
Not only did the researchers study the offspring of obese mothers, but they also looked at the effects of feeding the obese pregnant mothers a diet supplemented with substances that are known to donate chemical tags called methyl groups to areas of the DNA that regulate genes.. This supplement was able to reverse the effect of mom’s obesity on her pups.
“It was able to completely eliminate the obesogenic effect, or the obesity-promoting effect, of maternal obesity on the offspring,” Waterland says.
Waterland says it’s possible that DNA methylation plays a significant role in the development of the hypothalamus, which is the part of the brain that regulates appetite. And because the mice studied had genetic tendencies to overeat, it’s possible that the methyl supplements also played a role in the appetite part of the brain, causing a reversal in the obese offspring effect.
“Where my research is going now is to try to understand what are the mechanisms that regulate the hypothalamus, specifically expression of these very important genes, when are they established during development and how are they influenced by environment such as nutrition or maternal obesity,” explains Waterland.
Findings Support Maintaining Healthy Weights
One of the substances in the supplement fed to the mouse moms was folic acid, which women area already advised to take during pregnancy. But Waterland stresses that their findings can’t yet be extended to people. "The supplement we gave included other ingredients in addition to folic acid, so we don’t know whether it might be these other ingredients that are playing the key role. And also, we fundamentally don’t know whether these findings in a mouse model can be directly translated to humans," he says.
But he calls the possibility that supplements could eventually be designed to do the same in people, "tantalizing."
“If we can understand exactly how this supplement works and what it is doing, and if it indeed has the same types of properties in humans, it may someday be possible that an obese woman who is planning on becoming pregnant would be prescribed a type of special dietary supplement that would help to minimize the risk of her child becoming obese,” Waterland says.
For now, Waterland says his studies support recommendations that woman should aim for a healthy weight before becoming pregnant.
“Obese women who are planning on becoming pregnant should try to attain a healthy body weight before pregnancy in order to minimize the risk of pregnancy complications and also maximize the health of their baby,” Waterland says.
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