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Liver metabolic disruption induced after a single exposure to PCB126 in rats

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Abstract

Polychlorinated biphenyls (PCBs) have been recognized as metabolic disruptors. The liver plays a pivotal role in detoxification of an organism. Fatty liver results from altered intra-, and extra-hepatic mediators and is associated with increased glucose-related protein 78 (GRP78), commonly used as a marker for endoplasmic reticulum (ER) stress signaling. This pilot study aimed to study the effects of a single exposure on fatty liver metabolic parameters. The objective of the study is to characterize the effects of 3,3′,4,4′,5-pentachlorobiphenyl (PCB126) on ER stress protein chaperon GRP78 and CCAAT-enhancer-binding protein homologous protein (CHOP) and intra-hepatic mediators such as microsomal triglyceride transfer protein (MTP), sterol regulatory element-binding protein 1c (SREBP1c), and peroxisome proliferator-activated receptor alpha (PPARα), as well as extra-hepatic factors such as non-esterified fatty acid (NEFA) and tumor necrosis factor alpha (TNFα). Hepatic GRP78 mRNA and protein levels, indicating the presence of ER stress, were significantly increased following a single PCB126 exposure in rats. Intra-hepatic mechanisms such as lipoprotein secretion pathway (i.e., MTP), lipogenesis de novo (i.e., SREBP1c), and oxidation (i.e., PPARα) were altered in PCB126-treated rats. In addition, a state of inflammation measured by higher TNFα plasma levels was present in contaminated rats. These data indicate that a single injection of PCB126-modulated expression of GRP78 associated with hepatic ER stress and systemic inflammation in rats.

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Acknowledgments

This project was funded by the Natural Sciences and Engineering Research Council of Canada (NSERC 418312-2012) (to NAC).

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Authors and Affiliations

  1. Institut de recherche de l’Hôpital Montfort, Institut du savoir Montfort, 713 Montreal Road, Pavillon E, Ottawa, Ontario, K1K 0T2, Canada

    Natalie A. Chapados

  2. Shcool of Human Kinetics, Faculty of Health Sciences, University of Ottawa, Ottawa, Ontario, Canada

    Natalie A. Chapados

  3. La Cité, Ottawa, Ontario, Canada

    Marie-Pier Boucher

Authors
  1. Natalie A. Chapados
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  2. Marie-Pier Boucher
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Correspondence to Natalie A. Chapados.

Ethics declarations

All procedures were approved by the Animal Care Committee of the University of Ottawa and adhered to the guidelines established by the Canadian Council on Animal Care.

Funding

This project was funded by the Natural Sciences and Engineering Research Council of Canada (NSERC 418312-2012) (to NAC).

Conflict of interest

The authors declare that they have no conflict of interest.

Authors contribution

MPB carried out the molecular studies on rats and helped drafted the manuscript. NAC conceived the study and its design, as well ascoordinated and helped to draft the manuscript. All authors read and approved the final manuscript.

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Responsible editor: Markus Hecker

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Chapados, N.A., Boucher, MP. Liver metabolic disruption induced after a single exposure to PCB126 in rats. Environ Sci Pollut Res 24, 1854–1861 (2017). https://doi.org/10.1007/s11356-016-7939-8

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  • DOI: https://doi.org/10.1007/s11356-016-7939-8

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