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

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.