Effects of adipocyte aryl hydrocarbon receptor deficiency on PCB-induced disruption of glucose homeostasis in lean and obese mice

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

Research output: Contribution to journalArticlepeer-review

52 Scopus citations


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 (AhRfl/fl) mice but not in adipocyte AhR–deficient mice (AhRAdQ). Unexpectedly, AhRAdQ 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 AhRAdQ mice administered vehicle (VEH) exhibited increased body weight, adipose mass, adipose inflammation, and impaired glucose tolerance compared with AhRfl/fl controls. Impairment of glucose homeostasis in response to PCB-77 was not observed in obese mice of either genotype. However, upon weight loss, AhRfl/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 AhRAdQ 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.

Original languageEnglish
Pages (from-to)944-950
Number of pages7
JournalEnvironmental Health Perspectives
Issue number10
StatePublished - Oct 2015

Bibliographical note

Publisher Copyright:
© 2015, Public Health Services, US Dept of Health and Human Services. All rights reserved.

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis


Dive into the research topics of 'Effects of adipocyte aryl hydrocarbon receptor deficiency on PCB-induced disruption of glucose homeostasis in lean and obese mice'. Together they form a unique fingerprint.

Cite this