Exposure to low doses of Dechlorane Plus promotes adipose tissue dysfunction and glucose intolerance in male mice

2020-06-18

The prevalence of type 2 diabetes (T2D) continues to increase worldwide. It is well established that genetic susceptibility, obesity, overnutrition and a sedentary life style are risk factors for the development of T2D. However, more recently, studies have also proposed links between exposure to endocrine-disrupting chemicals (EDCs) and altered glucose metabolism. Human exposure to environmental pollutants suspected to have endocrine disruptor activity is ubiquitous. One such chemical is Dechlorane Plus, a flame retardant, that is now detected in humans and the environment. Here we show that exposure of mice to low, environmentally relevant doses of Dechlorane Plus (DP), promoted glucose intolerance in mice fed high fat diet independent of weight gain. Further, DP had pronounced effects on the adipose tissue, where it induced the development of hypertrophied white adipose tissue (WAT), and increased serum levels of resistin, leptin, and plasminogen activator inhibitor-1. Further, DP exposure induced “whitening” of brown adipose tissue (BAT), and reduced BAT uncoupling protein 1 expression. Importantly, some of these effects occurred even when the mice were fed regular, low fat, diet. Finally, WAT adipogenic markers were reduced with DP treatment in the WAT. We also show that, DP directly inhibited insulin signalling in murine adipocytes and human primary subcutaneous adipocytes in vitro. Taken together, our results show that the exposure to low and environmentally relevant levels of DP may contribute to the development of T2D.

Authors: Endocrinology. 2020 Jun 18;bqaa096. doi: 10.1210/endocr/bqaa096. Online ahead of print.
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