"We want to understand the mechanisms behind the current epidemic of childhood obesity," said Dr. Kjersti M. Aagaard-Tillery, assistant professor of obstetrics and gynecology at BCM. "What efforts can we take in pregnancy to affect this problem? Is it that the mom is obese or is exposure to a high fat diet the problem?"
A consortium of researchers from BCM, the University of Utah Health Sciences in Salt Lake and the Oregon National Primate Research Center teamed up to study what happens to the offspring of non-human primate mothers fed a diet consisting of 35 percent fat. When compared to those who ate a 13 percent fat diet, the offspring of these animals had non-alcoholic fatty liver disease (comparable to that found in obese human youngsters). In fact, their triglycerides (one form of fat measured in blood) were three times higher than those of the normal offspring.
In some cases, the mothers on the high fat diet did not become obese themselves but their offspring suffered the same ill effects as those of moms who did become obese.
At a molecular level, Aagaard and her collaborators found modifications in the DNA backbone – the histones – of the offspring of the mothers who ate a high fat diet. This is called an epigenetic change, which means that while it does not affect the DNA code per se, it still affects the way that the genes are regulated and the degree to which they are expressed (the so-called "histone code").
"We found that there were genes that were differentially regulated in the livers of the offspring whose mothers had a high fat diet, and that these changes were associated with histone alterations," she said. "The genes affected were not always those associated with obesity."
She is now trying to find out why these gene changes exist and how they might affect the animals later in life. She is interested in looking at whether they are the direct result of permanent modifications in the histones in both the liver and brain, and whether they further relate to specific changes in the chemical modifications (or methylation) of the regulatory regions of genes.
Others who took part in this work include Kevin Grove and Jacalyn Bishop of the Oregon Health Science University, Oregon National Primate Research Center and Xingrao Ke, Qi Fu, Robert McKnight, and Robert H. Lane of the University of Utah Health Sciences in Salt Lake.
Funding for this work came from the 2007 National Institutes of Health Director's New Innovators Award to Aagaard, the National Institute of Digestive and Diabetes and Kidney Diseases and the National Institute of Child Health and Human Development.