Fat associated with chemical changes in DNA that may help explain obesity-related disease

January 20, 2011
The research of Dr. Xiaoling Wang, genetic epidemiologist at the Medical College of Georgia's Georgia Prevention Institute, is providing insight as to how fat causes disease. Credit: Phil Jones, Campus Photographer

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 the top six genes and found again the distinctive methylation pattern in UBASH3A and TRIM3.

Wang now wants to clarify whether fat causes the DNA changes or vice versa and confirm that the changes contribute to the immune dysfunction associated with obesity.

She notes that because obesity does not always lead to related diseases, it's important to have a way to not just intervene, but to identify those most at risk. Factors such as fitness, body shape and environment probably are also predictors for related disease.

"... (T)he public health message of 'eat less and exercise more' appears to have fallen on deaf ears," Drs. Paul W. Franks and Charlotte Ling of Sweden's Skåne University Hospital, Lund University write in an accompanying editorial. "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 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." They note that Wang's study provides "tentative evidence" that methylation at the two gene sites may be implicated in obesity-related .

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5 / 5 (1) Jan 20, 2011
"Losing fat is very difficult; we know that"
nonsense, if you know simple rules, its easy.
I lost 25 kg (from 122 to 97kg now) just in 18 months.
Without diet or tedious exercises. I eat what I want, just replaced junk meals and added a physical activity for at least an hour a day (like walking or cycling). Thats it.
1 / 5 (1) Jan 20, 2011
Overall cause mortality isn't higher among heavier/fatter people, the inverse actually (except the very extremes obviously) . Just the causes of death are different.
If one calculates the vast sums wasted on sportrelated injuries for example, it easily balances out a correlation (no causation) between certain diseases and weight.

This study is yet another attempt to cash in on the obesity scare. Keep that grantmoney flowing we've got another tenuous link.

1 / 5 (1) Jan 20, 2011
If obesity isn't bad for your health, then how come I've never seen an obese centenarian.

(Maybe they all go through a massive diet just before the photo??)
not rated yet Jan 20, 2011
You mean to say all centenarians have their photo's made and you've seen them all?
Facts, look them up yourself: (if you put a link here you end up in spamcountry prison)
The majority of people in retirement homes are overweight, the oldest have the highest levels of cholesterol.
People with lower bodymasses suffer more from general diseases, take longer to recover, are more likely to have complications during/after surgery.

Sure fat augments the risk of certain specific diseases, but lowers the risk of most others balancing out in a positive effect for bodymasses around BMI 20-32.

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