title: Coplanar polychlorinated biphenyls impair glucose homeostasis in lean C57BL/6 mice and mitigate beneficial effects of weight loss on glucose homeostasis in obese mice.
abstract: BACKGROUND
  Previous studies demonstrated that coplanar polychlorinated biphenyls (PCBs) promote proinflammatory gene expression in adipocytes. PCBs are highly lipophilic and accumulate in adipose tissue, a site of insulin resistance in persons with type 2 diabetes.
  
  
  OBJECTIVE
  We investigated the in vitro and in vivo effects of coplanar PCBs on adipose expression of tumor necrosis factor α (TNF-α) and on glucose and insulin homeostasis in lean and obese mice.
  
  
  METHODS
  We quantified glucose and insulin tolerance, as well as TNF-α levels, in liver, muscle, and adipose tissue of male C57BL/6 mice administered vehicle, PCB-77, or PCB-126 and fed a low fat (LF) diet. Another group of mice administered vehicle or PCB-77 were fed a high fat (HF) diet for 12 weeks; the diet was then switched from HF to LF for 4 weeks to induce weight loss. We quantified glucose and insulin tolerance and adipose TNF-α expression in these mice. In addition, we used in vitro and in vivo studies to quantify aryl hydrocarbon receptor (AhR)-dependent effects of PCB-77 on parameters of glucose homeostasis.
  
  
  RESULTS
  Treatment with coplanar PCBs resulted in sustained impairment of glucose and insulin tolerance in mice fed the LF diet. In PCB-77-treated mice, TNF-α expression was increased in adipose tissue but not in liver or muscle. PCB-77 levels were strikingly higher in adipose tissue than in liver or serum. Antagonism of AhR abolished both in vitro and in vivo effects of PCB-77. In obese mice, PCB-77 had no effect on glucose homeostasis, but glucose homeostasis was impaired after weight loss.
  
  
  CONCLUSIONS
  Coplanar PCBs impaired glucose homeostasis in lean mice and in obese mice following weight loss. Adipose-specific elevations in TNF-α expression by PCBs may contribute to impaired glucose homeostasis.
authors.affiliation: Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, Kentucky 40536-0200, USA.
authors.forename: Nicki A
authors.initials: NA
authors.lastname: Baker
authors.forename: Michael
authors.initials: M
authors.lastname: Karounos
authors.forename: Victoria
authors.initials: V
authors.lastname: English
authors.forename: Jun
authors.initials: J
authors.lastname: Fang
authors.forename: Yinan
authors.initials: Y
authors.lastname: Wei
authors.forename: Arnold
authors.initials: A
authors.lastname: Stromberg
authors.forename: Manjula
authors.initials: M
authors.lastname: Sunkara
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Morris
authors.forename: Hollie I
authors.initials: HI
authors.lastname: Swanson
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Cassis
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D015431:Weight Loss / Q000502:physiology*
chemical_list: D011078:Polychlorinated Biphenyls; D005947:Glucose