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Identification of metabolic profiles associated with human exposure to perfluoroalkyl substances

Journal of Exposure Science & Environmental Epidemiology volume 29, pages 196–205 (2019)Cite this article

Abstract

Recent epidemiological studies suggest that human exposure to perfluoroalkyl substances (PFASs) may be associated with type 2 diabetes and other metabolic phenotypes. To gain further insights regarding PFASs exposure in humans, we here aimed to characterize the associations between different PFASs and the metabolome. In this cross-sectional study, we investigated 965 individuals from Sweden (all aged 70 years, 50% women) sampled in 2001–2004. PFASs were analyzed in plasma using isotope-dilution ultra-pressure liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS). Non-target metabolomics profiling was performed in plasma using UPLC coupled to time-of-flight mass spectrometry (UPLC-QTOFMS) operated in positive electrospray mode. Multivariate linear regression analysis was used to investigate associations between circulating levels of PFASs and metabolites. In total, 15 metabolites, predominantly from lipid pathways, were associated with levels of PFASs following adjustment for sex, smoking, exercise habits, education, energy, and alcohol intake, after correction for multiple testing. Perfluorononanoic acid (PFNA) and perfluoroundecanoic acid (PFUnDA) were strongly associated with multiple glycerophosphocholines and fatty acids including docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA). We also found that the different PFASs evaluated were associated with distinctive metabolic profiles, suggesting potentially different biochemical pathways in humans.

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Acknowledgements

This study received funding from the Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (FORMAS) under grant numbers 2015-756 and 2013-478. Tove Fall has personal grants from the Göran Gustafsson Foundation and the Swedish Research Council (2015–03477). We greatly acknowledge the contribution of Bert van Bavel (Norwegian Institute for Water Research, Oslo, Norway) with regard to the analytical methodology for PFASs. We greatly acknowledge Erik Lampa (Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden) for statistical assistance.

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Authors and Affiliations

  1. Department of Medical Sciences and Science for Life Laboratory, Molecular Epidemiology Unit, Uppsala University, Uppsala, Sweden

    Samira Salihovic & Tove Fall

  2. MTM Research Centre, School of Science and Technology, Örebro University, Örebro, Sweden

    Samira Salihovic, Tuulia Hyötyläinen & Anna Kärrman

  3. Massachusetts General Hospital, Harvard Medical School and Broad Institute, Boston, MA, USA

    Andrea Ganna

  4. Proteomics and Metabolomics Facility, Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO, USA

    Corey D. Broeckling & Jessica E. Prenni

  5. Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden

    P. Monica Lind

  6. Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA

    Erik Ingelsson

  7. Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden

    Lars Lind

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  1. Samira Salihovic
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Salihovic, S., Fall, T., Ganna, A. et al. Identification of metabolic profiles associated with human exposure to perfluoroalkyl substances. J Expo Sci Environ Epidemiol 29, 196–205 (2019). https://doi.org/10.1038/s41370-018-0060-y

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