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Polychlorinated biphenyl 126 exposure in L6 myotubes alters glucose metabolism: a pilot study

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Abstract

Polychlorinated biphenyls (PCBs) are increasingly recognized as metabolic disruptors. Due to its mass, skeletal muscle is the major site of glucose disposal. While muscle mitochondrial dysfunction and oxidative stress have been shown to play a central role in metabolic disease development, no studies to date have investigated the effect of PCB exposure on muscle energy metabolism and oxidative stress. In this pilot study, we tested the effect of exposure to PCB126 in L6 myotubes (from 1 to 2500 nM for 24 h) on mitochondrial function, glucose metabolism, and oxidative stress. Exposure to PCB126 had no apparent effect on resting, maximal, and proton leak-dependent oxygen consumption rate in intact L6 myotubes. However, basal glucose uptake and glycolysis were inhibited by 20–30 % in L6 myotubes exposed to PCB126. Exposure to PCB126 did not appear to alter skeletal muscle anti-oxidant defense or oxidative stress. In conclusion, our study shows for the first time that exposure to a dioxin-like PCB adversely affects skeletal muscle glucose metabolism. Given the importance of skeletal muscle in the maintenance of glucose homeostasis, PCB126 could play an important role in the development of metabolic disorders.

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Acknowledgments

This work was supported by operating fundings from Institut de Recherche de l’Hôpital Montfort to CA and NSERC (Natural Sciences and Engineering Research Council of Canada) Discovery grants (grant numbers 2015–06263 to CA and 418312–2012 to NC). Master scholarships to LN were provided by the Institut de Recherche de l’Hôpital Montfort and Canadian Institutes of Health Research (CIHR). The authors would like to thank Dr. Amira Klip for her generous gift of L6 myoblasts and Dr. Mary-Ellen Harper for the use of the XF-24 analyzer (Seahorse Bioscience) and the provision of her lab for radiation experiments.

Author contributions

Experiments were performed in Dr. Aguer’s laboratory at the Institut de Recherche de l’Hôpital Monfort (Ottawa, ON, Canada) except for Seahorse and radiation experiments that were conducted in Dr. Harper’s laboratory (Biochemistry, Microbiology, and Immunology Department, University of Ottawa). Conception and design of the experiments were done by NC and CA; collection, assembly, analysis, and interpretation of data by JFM, LN, AC, NC, and CA; drafting the article or revising it critically for important intellectual content by JFM, LN, AC, NC, and CA; and approval of the final version by JFM, LN, AC, NC, and CA.

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    1. Institut de recherche de l’Hôpital Montfort, 713 Montreal Rd, 1E113, Ottawa, ON, K1K 0T2, Canada

      Jean-François Mauger, Lucien Nadeau, Audrey Caron, Natalie Ann Chapados & Céline Aguer

    2. Faculty of Medicine, Biochemistry, Microbiology and Immunology Department, University of Ottawa, Ottawa, ON, K1H 8L1, Canada

      Lucien Nadeau & Céline Aguer

    3. Faculty of Health Sciences, Interdisciplinary School of Health Sciences, University of Ottawa, Ottawa, ON, K1S 5N5, Canada

      Audrey Caron

    4. Faculty of Health Sciences, School of Human Kinetics, University of Ottawa, Ottawa, ON, K1S 5N5, Canada

      Natalie Ann Chapados

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    1. Jean-François Mauger
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    Correspondence to Céline Aguer.

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    Jean-François Mauger and Lucien Nadeau contributed equally to this work.

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    Fig. S1

    Effect of 4- or 48-h PCB126 exposure in L6 myotube on mitochondrial respiration. Oxygen consumption rate measured in L6 myotubes exposed for the last 4 h (a) or 48 h (b) of differentiation to the vehicle (DMSO) or 100, 1000, or 2500 nM PCB126. Oxygen consumption rates were measured in resting, oligomycin (state 4), FCCP (maximal OCR), and anti-mycin A (non-mitochondrial OCR) conditions. Mean ± SEM. Each condition was done in five replicates (PPTX 40 kb)

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    Mauger, JF., Nadeau, L., Caron, A. et al. Polychlorinated biphenyl 126 exposure in L6 myotubes alters glucose metabolism: a pilot study. Environ Sci Pollut Res 23, 8133–8140 (2016). https://doi.org/10.1007/s11356-016-6348-3

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