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.
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.
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.
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
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.
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.
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.”
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.
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.
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
“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.
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.”