AUGUSTA, Ga. Fat appears to associate with some distinctive chemical changes in the DNA a finding that may help explain why obesity can increase the risk for chronic problems such as cardiovascular disease and diabetes, researchers report.
The finding, published in BMC Medicine, may one day help identify those at risk and reduce it, according to Dr. Xiaoling Wang, genetic epidemiologist at the Medical College of Georgia's Georgia Prevention Institute.
"Losing fat is very difficult; we know that. We also know it causes many diseases so we want to identify and target pathways to reduce those diseases," Wang said.
Fat used to be viewed as essentially padding and a ready energy source but scientists are learning it's more like a factory that makes chemicals and compounds such as hormones and proteins. Studies comparing two groups of obese versus lean teens found higher levels of chemical change, or methylation, in a portion of the UBASH3A gene and lower levels in part of the TRIM3 gene.
Both genes are known to have roles in regulating the immune system, which is often dysregulated in obese individuals. Dysregulation can result in a level of chronic inflammation that contributes to diseases such as cardiovascular disease, diabetes and cancer. Methylation can impact immune function by affecting gene expression levels which ultimately impacts downstream functions of the proteins produced by genes.
"You need to know disease pathways to find novel medications," Wang said. "We generally know they have a dysregulation of the immune function, but we didn't know the specific site." She believes she found at least two sites in the UBASH3A and TRIM3 gene. Her initial search was broad: a genome-wide screen of seven obese and seven lean teens that enabled her to identify genes most different between the two. She ranked the differences and, in a much larger study of 46 obese and 46 lean controls, looked at the same sites in
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Medical College of Georgia