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Cell-free DNA triggers obesity-related inflammation

The release of cell-free DNA from dying fat cells may contribute to obesity-linked tissue inflammation and metabolic dysfunction, a new study in mice suggests. The findings help to explain why obese individuals tend to suffer from chronic inflammation, and point to a specific protein called TLR9 as a possible therapeutic target. Chronic inflammation is a hallmark of obesity and obesity-related complications such as insulin resistance, yet the underlying mechanism remains largely unknown.

The release of cell-free DNA from degenerating fat tissue cells called adipocytes may contribute to obesity-linked inflammation, Sachiko Nishimoto et al. now show. In mice that were fed a high-fat diet for twelve weeks, the authors observed increased expression of the TLR9 protein in adipose tissue, as well as higher levels of circulating cell-free DNA.

Taking a closer look, the authors determin ed that macrophages, a key player in adipose tissue inflammation, express TLR9, adding further evidence of the protein’s role in inflammation. Treating the mice with a TLR9-inhibiting compound reduced the accumulation of macrophages in adipose tissue and improved insulin resistance. And analyzing human plasma samples, the authors found that circulating cell-free DNA positively correlated with obesity and insulin resistance in patients. The results hint that circulating cell-free DNA released by obesity-triggered adipocyte degeneration plays a causal role in the development of tissue inflammation.

Article: Obesity-induced DNA released from adipocytes stimulates chronic adipose tissue inflammation and insulin resistance, Sachiko Nishimoto, Daiju Fukuda, Yasutomi Higashikuni, Kimie Tanaka, Yoichiro Hirata, Chie Murata, Joo-ri Kim-Kaneyama, Fukiko Sato, Masahiro Bando, Shusuke Yagi, Takeshi Soeki, Tetsuya Hayashi, Issei Imoto, Hiroshi Sakaue, Michio Shimabukuro and Masataka Sata, Science Advances, doi: 10.1126/sciadv.1501332, published 25 March 2016.