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Mechanism of BDE209-induced impaired glucose homeostasis based on gene microarray analysis of adult rat liver

  • Toxicogenomics
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Abstract

Several persistent organic pollutants are reported to be potentially associated with the risk of human diabetes that has become rapidly epidemic in China currently. 2,2′,3,3′,4,4′,5,5′,6,6′-decabromodiphenyl ether (BDE209) is commercially most important both in the production and in the use of polybrominated diphenyl ethers (PBDEs). It might bioaccumulate in wildlife and human and is the only PBDEs mixture still used today. In the present study, male adult rats treated with BDE209 (0, 0.05, 1, and 20 mg/kg) for 8 weeks were used to explore the effects of BDE209 on glucose homeostasis and possible mechanisms; 0.05 mg/kg of BDE209 induced dose-related hyperglycemia. Then, we performed the full-genome gene expression microarrays, gene ontology analysis, and pathway analysis in this group and control. BDE209 induced 1,257 liver gene transcript changes, and 18 canonical pathways were significantly enriched. Four of them were involved in immune diseases, including autoimmune thyroid disease, graft-versus-host disease, allograft rejection, and type I diabetes mellitus (T1MD), which was confirmed by the decrease in serum insulin. Subsequently, gene act network and gene co-expression network found that some MHC molecules and TNF-α were involved in T1DM pathway, which was then confirmed by the increase in serum TNF-α. Additionally, reduced glutathione and superoxide dismutase in plasma indicated that oxidative damage might partly contribute to BDE209-induced hyperglycemia. The results of this study provide some new experimental evidence that the exposure to high levels of BDE209 may contribute to the onset of diabetes in human populations. Further work needs to be done to confirm this link.

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Abbreviations

BDE209:

2,2′,3,3′,4,4′,5,5′,6,6′-decabromodiphenyl ether

PBDEs:

Polybrominated diphenyl ethers

OH-BDEs:

Hydroxylated polybrominated diphenyl ether

POPs:

Persistent organic pollutants

CHOL:

Total cholesterol

TG:

Triglyceride

ROS:

Reactive oxygen species

MDA:

Malondialdehyde

GSH:

Reduced glutathione

SOD:

Superoxide dismutase

TNF-α:

Tumor necrosis factor α

MHC:

Major histocompatibility complex

T1DM:

Type I diabetes mellitus

NOD:

Nonobese diabetic

GO:

Gene ontology

ELISA:

Enzyme-linked immunosorbent assays

qRT-PCR:

Real-time quantitative reverse transcription polymerase chain reaction

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Acknowledgments

The authors wish to thank Drs. Dai Chen and Jie Zong (Novel Bioinformatics Ltd., Co, Shanghai, China) for their technical assistance in bioinformatics analysis. This work was supported by Environmental Protection Research Special Funds for Public Welfare Projects (200909054), National 973 program (2009CB941701), National Natural Science Foundation of China (81172695, 30972508), Doctoral Fund of Ministry of Education of China (20093234110002), Six talents peak project of Jiangsu province (DG216D5047), and a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), China.

Conflict of interest

No competing financial interests exist.

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Authors and Affiliations

  1. Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 818 East Tiangyuan Rd., Nanjing, 211166, China

    Zhan Zhang, Zhen-Zhen Sun, Xue Xiao, Xi-Chen Wang, Jun Gu, Liang-Lin Qiu, Xu-Hui Zhang, Xinru Wang & Shou-Lin Wang

  2. Stem Cell Research Center and Department of Cell Biology, Peking University Health Science Center, Beijing, 100083, China

    Shixin Zhou

  3. Lake Research Center, Chinese Research Academy of Environmental Sciences, Beijing Anwai Beiyuan, Beijing, 100012, China

    Qiujin Xu & Binghui Zhen

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  1. Zhan Zhang
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Correspondence to Shou-Lin Wang.

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Zhan Zhang and Zhen-Zhen Sun contributed equally to this work.

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Zhang, Z., Sun, ZZ., Xiao, X. et al. Mechanism of BDE209-induced impaired glucose homeostasis based on gene microarray analysis of adult rat liver. Arch Toxicol 87, 1557–1567 (2013). https://doi.org/10.1007/s00204-013-1059-8

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