Polybrominated diphenyl ether congener, BDE-47, impairs insulin sensitivity in mice with liver-specific Pten deficiency

多溴二苯醚同源物 BDE-47 会损害肝脏特异性 Pten 缺乏症小鼠的胰岛素敏感性

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作者:Rebecca L McIntyre, Heidi L Kenerson, Savitha Subramanian, Shari A Wang, Machiko Kazami, Heather M Stapleton, Raymond S Yeung

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

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.

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.

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