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Cell-free DNA

Cell-free DNA may be involved in inflammation in obese patients

Study may provide a novel mechanism for the development of sterile inflammation in adipose tissue and a potential therapeutic target for insulin resistance

A team of Japanese researchers has found that as fat cells die due to an increase in obesity, more cell-free DNA is released into tissue causing inflammation. In their paper ‘Obesity-induced DNA released from adipocytes stimulates chronic adipose tissue inflammation and insulin resistance’, published in the journal Science Advances, the team describes their study of mice, inflamed tissue and Toll—like receptor 9 (TLR9).

People who gain weight become more susceptible to chronic inflammation and there is a link between inflammation and the protein TLR9, as well as a link between obesity, inflammation and insulin resistance (the underlying cause of diabetes). In this new study, the researchers found that as people become obese more and more cell-free DNA is released into nearby tissue as fat cells degenerate and break apart, the result is inflammation, an increased expression of TLR9 and insulin resistance.

The team conducted tests with mice that involved causing them to express more or less TLR9, higher levels were found in obese mice but reducing the levels even in obese mice, led to less inflation and insulin resistance.

More specifically, the researchers found that the expression of TLR9 had an impact on the amount of accumulation of macrophages in murine fat tissue. Mice that were made obese, but who were caused to express less TLR9, had less accumulation of macrophages in their fat tissues, than those with higher levels of TLR9, which caused them to be more sensitive to insulin. Re-introducing TLR9, on the other hand, caused the inflammation and insulin resistance to rebound. This suggests that developing a therapy that reduces TLR9 levels in humans may help to reduce inflammation due to obesity.

The team also found that people with higher than normal levels of visceral fat in their blood also had increased levels of cell-free DNA suggesting the findings in mice likely compare to humans. They also note that it is still not clear why it is that certain fat cells die off as people become obese or whether the cell-free DNA that circulates in the body has any sort of impact on other tissue types.

The researchers concluded that, “Our study may provide a novel mechanism for the development of sterile inflammation in adipose tissue and a potential therapeutic target for insulin resistance.”

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