Effects of Adipocyte Aryl Hydrocarbon Receptor Deficiency on PCB-Induced Disruption of Glucose Homeostasis in Lean and Obese Mice

Authors

Nicki A. Baker, University of KentuckyFollow
Robin Shoemaker, University of KentuckyFollow
Victoria English, University of KentuckyFollow
Nika Larian, University of KentuckyFollow
Manjula Sunkara, University of KentuckyFollow
Andrew J. Morris, University of KentuckyFollow
Mary Walker, University of New Mexico
Frederique Yiannikouris, University of KentuckyFollow
Lisa A. Cassis, University of KentuckyFollow

Abstract

BACKGROUND: Coplanar polychlorinated biphenyls (PCBs) promote adipocyte inflammation and impair glucose homeostasis in lean mice. The diabetes-promoting effects of lipophilic PCBs have been observed only during weight loss in obese mice. The molecular mechanisms linking PCB exposures to impaired glucose metabolism are unclear.

OBJECTIVES: In this study we tested the hypothesis that coplanar PCBs act at adipocyte aryl hydrocarbon receptors (AhRs) to promote adipose inflammation and impair glucose homeostasis in lean mice and in obese mice during weight loss.

METHODS AND RESULTS: PCB-77 administration impaired glucose and insulin tolerance in LF (low fat diet)-fed control (AhR^fl/fl) mice but not in adipocyte AhR-deficient mice (AhR^AdQ). Unexpectedly, AhR^AdQ mice exhibited increased fat mass when fed a standard LF or high fat (HF) diet. In mice fed a HF diet, both genotypes became obese, but AhR^AdQ mice administered vehicle (VEH) exhibited increased body weight, adipose mass, adipose inflammation, and impaired glucose tolerance compared with AhR^fl/fl controls. Impairment of glucose homeostasis in response to PCB-77 was not observed in obese mice of either genotype. However, upon weight loss, AhR^fl/fl mice administered PCB-77 exhibited increased abundance of adipose tumor necrosis factor-α (TNF-α) mRNA and impaired glucose homeostasis compared with those administered VEH. In contrast, PCB-77 had no effect on TNF-α or glucose homeostasis in AhR^AdQ mice exhibiting weight loss.

CONCLUSIONS: Our results demonstrate that adipocyte AhR mediates PCB-induced adipose inflammation and impairment of glucose homeostasis in mice. Moreover, deficiency of AhR in adipocytes augmented the development of obesity, indicating that endogenous ligand(s) for AhR regulate adipose homeostasis.

Document Type

Article

Publication Date

10-1-2015

Notes/Citation Information

Published in Environmental Health Perspectives, v. 123, no. 10, p. 944-950.

Reproduced from Environmental Health Perspectives, a public domain publication of the U.S. Federal Government. http://dx.doi.org/10.1289/ehp.1408594

Digital Object Identifier (DOI)

http://dx.doi.org/10.1289/ehp.1408594

Funding Information

This research was supported by National Institute of Environmental Health Sciences, National Institutes of Health (NIH), grant P42 ES 007380 (L.A.C.) and through research cores supported by NIH grant P20 GM103527-06 (L.A.C.); and trainee support (N.A.B.) was provided by NIH T32 3048107792 (L.A.C.).

Repository Citation

Baker, Nicki A.; Shoemaker, Robin; English, Victoria; Larian, Nika; Sunkara, Manjula; Morris, Andrew J.; Walker, Mary; Yiannikouris, Frederique; and Cassis, Lisa A., "Effects of Adipocyte Aryl Hydrocarbon Receptor Deficiency on PCB-Induced Disruption of Glucose Homeostasis in Lean and Obese Mice" (2015). Saha Cardiovascular Research Center Faculty Publications. 15.
https://uknowledge.uky.edu/cvrc_facpub/15