14 DAY TRIAL // Research carried out by a genetic epidemiologist at the Medical College of Georgia, at Georgia Prevention Institute, concluded that fat is somehow linked to certain chemical changes in the DNA, and this could be the explanation for the high risk of chronic issues, like cardiovascular disease and diabetes, in obese people.
This finding could one day help identify people at risk and prevent the damage instead of just treating it, said Dr. Xiaoling Wang.
She added that “losing fat is very difficult; we know that,” but “we also know it causes many diseases so we want to identify and target pathways to reduce those diseases.
“You need to know disease pathways to find novel medications,” she added.
“We generally know they have a dysregulation of the immune function, but we didn't know the specific site.”
Dr Wang believes she has found at least two sites in the UBASH3A and TRIM3 gene.
She started by carrying out a genome-wide screen of 7 obese and 7 lean adolescents, which allowed her to identify the most different genes between the two groups.
Then, she ranked these differences, and in a larger study, involving 46 obese and 46 lean controls, she looked at the same sites in the top six genes, where she found the distinctive chemical change (methylation) pattern in UBASH3A and TRIM3.
Previously, fat was not considered something very serious for people's health, but now, scientists found out that fat is more like a source of chemicals and compounds, such as hormones and proteins.
In these two groups of obese versus lean teens, the levels of chemical change were very high in a part of the UBASH3A gene, and lower levels in a portion of the TRIM3 gene.
Both these genes are responsible for regulating the immune system, which in obese people is often dysregulated.
This dysregulation can trigger a level of chronic inflammation, contributing to cardiovascular disease, diabetes and even cancer.
Methylation can affect gene expression and, subsequently, impact downstream functions of the proteins produced by the genes.
In an accompanying editorial, Dr Paul W. Franks and Dr Charlotte Ling of Sweden's Skåne University Hospital, Lund University write that “… (T)he public health 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.”
They say that Wang's study provides 'tentative evidence' that DNA methylation at the two gene sites could be implicated in obesity-related disease.
Wang's next step is to clarify whether fat causes changes in the DNA or viceversa, and also to confirm that these changes contribute to the immune dysfunction related to obesity.
She notes that identifying people at risk is very important, since obesity does not always lead to related disease, and there might be other factors that can predict disease, like fitness, body shape and environment.
The findings were published in BMC Medicine.