Building Better Babies 

How Obesity Develops In the Womb

By Mark Couch

(December 2015) The children of obese mothers are more likely to become obese themselves in part due to traits they inherit while they are still in the womb, according to research presented earlier this year by a University of Colorado School of Medicine scientist.

Kristen Boyle, PhD, assistant professor of pediatrics, identified some of these traits by studying stem cells from umbilical cords and she hopes that by identifying a cause for greater obesity risk future research could inform ways to break the chain of obesity.

“My goal would be to introduce exercise or dietary interventions during pregnancy in obese mothers to see if there was the capacity to ameliorate any ill effects of the womb environment and hopefully then the trajectory of obesity for the child,” says Boyle.

Boyle and her team took stem cells from donated umbilical cords of babies of normal-weight and obese mothers and grew those cells into fat and muscle cells in the lab. The researchers found a 30 percent higher fat content in both the fat and muscle cells of children of obese mothers compared with the cells of children of normal-weight mothers, and the fat content of the cells corresponded to the fat mass of the babies. Boyle presented the finding at the American Diabetes Association’s 75th Scientific Sessions in summer 2015. It was one of eight abstracts, from more than 3,000 submitted, selected for presentation.

“I think people were excited, but I wouldn’t necessarily say they were surprised because the research in animal models has been leading up to this for a long while,” says Boyle.

“What makes this research exciting is that, by using this infant stem cell model we can begin to address the same questions in humans as have been done in the animals. Using these cells, we may soon be able to define why children born to obese mothers are at increased risk of developing obesity and metabolic disease. In the same vein, we may be able to identify specific characteristics from mom or the intrauterine environment that are contributing to these risk factors in the baby.”

Boyle’s research training began with clinical intervention studies using exercise and nutrition.

“That’s one of the reasons I really wanted to do this,” she says. “The whole impetus for looking at these infant stem cells was so that I could find stem cell markers associated with obesity in mom but also with the outcomes in the children later in life, then maybe we could use them to understand how interventions in pregnancy affect outcomes in the children.”

Boyle earned a BS in exercise physiology and nutrition from the University of Massachusetts at Amherst in 2001, a master’s in exercise physiology from Ohio University and a PhD in bioenergetics from East Carolina University.

“Even as an undergrad, I was always interested in scientific research and knew this type of career would be a good fit for me,” says Boyle.

 “I came to Anschutz to complete my post-doc studying gestational diabetes with Jed Friedman,” says Boyle. “He had recently begun work in this field of fetal programming, aiming to understand how the environment in utero affects the disease risk for the child later in life, particularly for diseases such as obesity, diabetes, or cardiovascular disease.”

Friedman, PhD, professor of pediatrics, biochemistry and molecular genetics and director of the NIH Center for Human Nutrition Research Metabolism Core Laboratory, says, “We’re trying to build better babies.”

He calls Boyles work “groundbreaking” in its exploration of the pathways for obesity and how they might be modified.

Previously, while at East Carolina, Boyle had studied stem cells cultured from the muscle biopsy tissue of adult patients.

“The interesting thing about these adult stem cells is that they retain metabolic characteristics from their donor,” Boyle says. “What we see with obese adults is that their muscle has less capacity to use fats. And we see those same characteristics in stem cells cultured from their muscle. This was a very interesting concept to me. How are these cells retaining metabolic characteristics?

“Did the cells always have these characteristics, providing clues as to why these individuals became obese? Or was there something in the adult stem cells that changed when the individual became obese? We don’t really know the answer to this question and I decided that best place to start would be at the beginning.”

Obviously that’s easier said than done.

“I really didn’t have a good way to test cellular metabolism in infants,” Boyle says. “We can’t take biopsies from babies, so how do we perform these invasive metabolic measures that are not only my expertise, but may be very informative as to the metabolic disease risk of these babies when they grow up?

“I started by reading some papers from other scientists who were culturing stem cells from umbilical cord tissue of newborn babies. But mostly these researchers were using the cells for regenerative medicine or tissue engineering. No one was really looking at whether these cells were in any way reflective of the baby. So I joined those two ideas together.”

At the University of Colorado Anschutz Medical Campus, she found the infrastructure was already in place to help with the research she wanted to do and a group of researchers working on obesity-related issues.

Boyle’s research is part of an ancillary project to the Healthy Start study, led by principal investigator Dana Dabelea, MD, PhD, in the Colorado School of Public Health. It is a 10-year study funded by the National Institutes of Health aimed at understanding the contribution of metabolic and behavioral factors during pregnancy to the development of obesity, insulin resistance and inflammatory markers in newborns and infants. The Healthy Start study is following more than 1,400 ethnically diverse pregnant women to assess the impact of intrauterine exposures on neonatal outcomes.

“My research would not be nearly as successful without using the infrastructure of the Healthy Start study,” Boyle says. “As a young investigator coming in, there was no way I could have obtained so many samples from such well-characterized moms and babies to really help my research get off the ground.

“Similar types of research are performed at other hospitals and universities around the world, but at these places there may be only a handful of investigators engaged in pregnancy and fetal programming research. Here, I think we have a much larger con-centration of investigators performing research in pre-conception, during pregnancy, and in infancy and early childhood—from basic science to clinical intervention to epidemiology. And all of this is done with the goal of improving outcomes for healthier children and healthier families. By working together, the scientists here at Anschutz have created a very collaborative research environment that fosters scientific discussion, which in turn fosters better science.”