Coplanar Polychlorinated Biphenyls Impair Glucose Homeostasis in Lean C57BL/6 Mice and Mitigate Beneficial Effects of Weight Loss on Glucose Homeostasis in Obese Mice
Nicki A. Baker,1 Michael Karounos,1 Victoria English,1 Jun Fang,2 Yinan Wei,2 Arnold Stromberg,3 Manjula Sunkara,4 Andrew J. Morris,4 Hollie I. Swanson,5 and Lisa A. Cassis1,5
1Graduate Center for Nutritional Sciences, 2Department of Chemistry, 3Department of Statistics, 4Division of Cardiovascular Medicine, and 5Department of Molecular and Biomedical Pharmacology, University of Kentucky, Lexington, Kentucky, USA
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.
Objectives: 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.
Key words: adipose, diabetes, glucose tolerance, polychlorinated biphenyl.
Environ Health Perspect 121:105–110 (2013). http://dx.doi.org/10.1289/ehp.1205421 [Online 24 October 2012]
Address correspondence to L.A. Cassis, Department of Molecular and Biomedical Pharmacology, University of Kentucky, Room 521b, Wethington Building, 900 S. Limestone, Lexington, KY 40536-0200 USA. Telephone: (859) 323-4933, ext 81400. Fax: (858) 257-3646. E-mail: firstname.lastname@example.org
Supplemental Material is available online (http://dx.doi.org/10.1289/ehp.1205421).
This work was supported by grant P42ES007380 from the National Institute of Environmental Health Sciences, National Institutes of Health, and through core services supported by a grant from the National Institute of General Medical Sciences (8 P20 GM103527-05).
The author’s freedom to design, conduct, interpret, and publish research was not compromised by any controlling sponsor as a condition of review or publication.
The authors declare they have no actual or potential competing financial interests.
Received 3 May 2012; Accepted 24 October 2012; Online 24 October 2012.
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