Obesity related diseases linked to DNA methylation.
Obesity related diseases are now linked to changes from DNA methylation that might explain why they occur.
The findings that fat and gene dysregulation occur together, raising the chances of heart disease, cancer and diabetes, could lead to new prevention tools.
The discovery comes from researchers at the Medical College of Georgia's Georgia Prevention Institute. According to Dr. Xiaoling Wang, genetic epidemiologist at the 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."
In the study, researchers compared lean teenagers to an obese group. They found higher levels of chemical changes that occur in fat, known as methylation, in a portion of the UBASH3A gene, and lower levels in part of the TRIM3 gene.
Both of the genes play a role in immune function, but the scientists aren't sure whether fat causes the DNA changes, or if gene dysregulation from DNA methylation causes obesity. The researchers plan more studies to clarify which comes first.
Dysregulation of the genes associated with obesity promotes inflammation that might explain the higher risk of heart disease and diabetes - but not in everyone.
Understanding more about the DNA methylation pattern and the specific genes that are affected, could lead to new ways to identify obese individuals at highest risk for chronic disease. Dr. Wang explains, "We generally know they have a dysregulation of the immune function, but we didn't know the specific site."
In an accompanying editorial, Drs. Paul W. Franks and Charlotte Ling of Sweden's Skåne University Hospital, Lund University write, "...the message of 'eat less and exercise more' appears to have fallen on deaf ears. Thus, despite the apparently simple explanation and remedy for obesity, this knowledge is not enough. We are saddled with a challenge, which is to unravel the mechanisms by which obesity emerges and to understand how its presence causes disease and death, with the hope that somewhere within the details hides the solution to the problem."
The researchers plan to confirm DNA methylation changes are the cause of obesity related diseases. The hope is to find ways to intervene. Dr. Wang notes obesity doesn't always cause disease, making it important to find out who is at highest risk.
BMC Medicine 2010, 8:87doi:10.1186/1741-7015-8-87