title: Polybrominated diphenyl ether congener, BDE-47, impairs insulin sensitivity in mice with liver-specific Pten deficiency.
abstract: 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.
authors.affiliation: Department of Surgery, University of Washington, 1959 NE Pacific, Seattle, WA 98195 USA.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: McIntyre
authors.affiliation: Department of Surgery, University of Washington, 1959 NE Pacific, Seattle, WA 98195 USA.
authors.forename: Heidi L
authors.initials: HL
authors.lastname: Kenerson
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA USA.
authors.forename: Savitha
authors.initials: S
authors.lastname: Subramanian
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA USA.
authors.forename: Shari A
authors.initials: SA
authors.lastname: Wang
authors.affiliation: Department of Surgery, University of Washington, 1959 NE Pacific, Seattle, WA 98195 USA.
authors.forename: Machiko
authors.initials: M
authors.lastname: Kazami
authors.affiliation: Nicholas School of Environment, Duke University, Durham, NC USA.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Stapleton
authors.affiliation: Department of Surgery, University of Washington, 1959 NE Pacific, Seattle, WA 98195 USA.
authors.forename: Raymond S
authors.initials: RS
authors.lastname: Yeung
keywords: BDE-47; Insulin resistance; Metabolic disruption; Pten-/- mice; Tsc1-/- mice