Background
The potential health effects of polybrominated diphenyl ethers (PBDEs) that are widely used as flame-retardants in consumer products have been attributed, in part, to their endocrine disrupting properties. The purpose of this study is to examine the in vivo effects of an early exposure to PBDEs on the development of insulin resistance in mice.
Results
The metabolic consequences of BDE-47 in mice with varying insulin sensitivities secondary to liver-specific activation of Akt ( Pten fl/fl ; Alb Cre ) and mTORC1 ( Tsc1 fl/fl ; Alb Cre ) as well as wild-type littermates, were studied. BDE-47, a dominant congener of PBDE, was given daily (1 mg/kg/day) for six weeks by oral gavage in young mice following weaning.
At the end of the exposure, there were no significant differences in total body, liver, or white adipose tissue weights between the BDE-47-treated vs. DMSO-treated mice for each respective genotype. Metabolic studies revealed significant impairment in insulin sensitivity in the BDE-47-treated Pten fl/fl ; Alb Cre mice, but not in wild-type or Tsc1 fl/fl ; Alb Cre mice. This was not accompanied by significant alterations in plasma insulin levels or hepatic triglyceride accumulation in the Pten fl/fl ; Alb Cre mice. The mean plasma BDE-47 level in the wild-type mice was 11.7 ± 2.9 ng/g (wet weight).
Conclusions
Our findings indicate that BDE-47 exposure during the early post-natal period induces a mild disturbance in glucose metabolism in susceptible mice with increased baseline insulin sensitivity. These results suggest an interaction between BDE-47 and genetic factors that regulate insulin signaling, which may result in long-term consequences.