Samira Salihovic1, Andrea Ganna2, Tove Fall3, Corey D Broeckling4, Jessica E Prenni4, Bert van Bavel5, P Monica Lind6, Erik Ingelsson7, Lars Lind8. 1. Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden; MTM Research Centre, School of Science and Technology, Örebro University, Örebro, Sweden. Electronic address: samira.salihovic@medsci.uu.se. 2. Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, MA 02142, USA. 3. Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden. 4. Proteomics and Metabolomics Facility, Colorado State University, Fort Collins, CO, USA. 5. MTM Research Centre, School of Science and Technology, Örebro University, Örebro, Sweden. 6. Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University Hospital, Uppsala, Sweden. 7. Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden; Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. 8. Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
Abstract
BACKGROUND: Dichlorodiphenyldichloroethylene (p,p'-DDE) and hexachlorobenzene (HCB) are organochlorine pesticides with well-known endocrine disrupting properties. Exposure to p,p'-DDE and HCB concerns human populations worldwide and has been linked to metabolic disorders such as obesity and type 2 diabetes, but details about these associations in humans from the general population are largely unknown. OBJECTIVES: We investigated the associations between p,p'-DDE and HCB exposure and global metabolomic profiles in serum samples from 1016 participants from the Swedish population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. METHODS: HCB and p,p'-DDE levels were determined using gas chromatography coupled to high-resolution mass spectrometry (GC-HRMS). Metabolite levels were determined by using a non-targeted metabolomics approach with ultra-performance liquid chromatography coupled to time-of- flight mass spectrometry (UPLC-TOFMS). Association analyses were performed using multivariate linear regression. RESULTS: We found circulating levels of p,p-DDE and HCB to be significantly associated with circulating levels of 16 metabolites following adjustment for age, sex, education level, exercise habits, smoking, energy intake, and alcohol intake. The majority of the 16 metabolites belong to lipid metabolism pathways and include fatty acids, glycerophospholipids, sphingolipids, and glycerolipids. Overall, p,p'-DDE and HCB levels were found to be correlated to different metabolites, which suggests that different metabolic fingerprints may be related to circulating levels of these two pesticides. CONCLUSIONS: Our findings establish a link between human exposure to organochlorine pesticides and metabolites of key metabolic processes mainly related to human lipid metabolism.
BACKGROUND:Dichlorodiphenyldichloroethylene (p,p'-DDE) and hexachlorobenzene (HCB) are organochlorine pesticides with well-known endocrine disrupting properties. Exposure to p,p'-DDE and HCB concerns human populations worldwide and has been linked to metabolic disorders such as obesity and type 2 diabetes, but details about these associations in humans from the general population are largely unknown. OBJECTIVES: We investigated the associations between p,p'-DDE and HCB exposure and global metabolomic profiles in serum samples from 1016 participants from the Swedish population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. METHODS:HCB and p,p'-DDE levels were determined using gas chromatography coupled to high-resolution mass spectrometry (GC-HRMS). Metabolite levels were determined by using a non-targeted metabolomics approach with ultra-performance liquid chromatography coupled to time-of- flight mass spectrometry (UPLC-TOFMS). Association analyses were performed using multivariate linear regression. RESULTS: We found circulating levels of p,p-DDE and HCB to be significantly associated with circulating levels of 16 metabolites following adjustment for age, sex, education level, exercise habits, smoking, energy intake, and alcohol intake. The majority of the 16 metabolites belong to lipid metabolism pathways and include fatty acids, glycerophospholipids, sphingolipids, and glycerolipids. Overall, p,p'-DDE and HCB levels were found to be correlated to different metabolites, which suggests that different metabolic fingerprints may be related to circulating levels of these two pesticides. CONCLUSIONS: Our findings establish a link between human exposure to organochlorine pesticides and metabolites of key metabolic processes mainly related to humanlipid metabolism.
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