title: Impaired lipid and glucose homeostasis in hexabromocyclododecane-exposed mice fed a high-fat diet.
abstract: BACKGROUND
  Hexabromocyclododecane (HBCD) is an additive flame retardant used in the textile industry and in polystyrene foam manufacturing. Because of its lipophilicity and persistency, HBCD accumulates in adipose tissue and thus has the potential of causing metabolic disorders through disruption of lipid and glucose homeostasis. However, the association between HBCD and obesity remains unclear.
  
  
  OBJECTIVE
  We investigated whether exposure to HBCD contributes to initiation and progression of obesity and related metabolic dysfunction in mice fed a normal diet (ND) or a high-fat diet (HFD).
  
  
  METHODS
  Male C57BL/6J mice were fed a HFD (62.2 kcal% fat) or a ND and treated orally with HBCD (0, 1.75, 35, or 700 μg/kg body weight) weekly from 6 to 20 weeks of age. We examined body weight, liver weight, blood biochemistry, histopathological changes, and gene expression profiles in the liver and adipose tissue.
  
  
  RESULTS
  In HFD-fed mice, body and liver weight were markedly increased in mice treated with the high (700 μg/kg) and medium (35 μg/kg) doses of HBCD compared with vehicle. This effect was more prominent in the high-dose group. These increases were paralleled by increases in random blood glucose and insulin levels and enhancement of microvesicular steatosis and macrophage accumulation in adipose tissue. HBCD-treated HFD-fed mice also had increased mRNA levels of Pparg (peroxisome proliferator-activated receptor-γ) in the liver and decreased mRNA levels of Glut4 (glucose transporter 4) in adipose tissue compared with vehicle-treated HFD-fed mice.
  
  
  CONCLUSIONS
  Our findings suggest that HBCD may contribute to enhancement of diet-induced body weight gain and metabolic dysfunction through disruption of lipid and glucose homeostasis, resulting in accelerated progression of obesity.
  
  
  BACKGROUND
  Yanagisawa R, Koike E, Win-Shwe TT, Yamamoto M, Takano H. 2014. Impaired lipid and glucose homeostasis in hexabromocyclododecane-exposed mice fed a high-fat diet. Environ Health Perspect 122:277-283; http://dx.doi.org/10.1289/ehp.1307421.
authors.affiliation: Center for Environmental Health Sciences, National Institute for Environmental Studies, Tsukuba, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Yanagisawa
authors.forename: Eiko
authors.initials: E
authors.lastname: Koike
authors.forename: Tin-Tin
authors.initials: TT
authors.lastname: Win-Shwe
authors.forename: Megumi
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Takano
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D059305:Diet, High-Fat / Q000009:adverse effects*; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000633:toxicity*; D005411:Flame Retardants / Q000633:toxicity; D006706:Homeostasis / Q000187:drug effects*; D006842:Hydrocarbons, Brominated / Q000633:toxicity*; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008659:Metabolic Diseases / Q000139:chemically induced*; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000139:chemically induced*; D016133:Polymerase Chain Reaction; D059467:Transcriptome / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D004785:Environmental Pollutants; D005411:Flame Retardants; D006842:Hydrocarbons, Brominated; C089796:hexabromocyclododecane