title: The metabolic fingerprint of p,p'-DDE and HCB exposure in humans.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: 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.
authors.forename: Samira
authors.initials: S
authors.lastname: Salihovic
authors.affiliation: 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.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ganna
authors.affiliation: Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Tove
authors.initials: T
authors.lastname: Fall
authors.affiliation: Proteomics and Metabolomics Facility, Colorado State University, Fort Collins, CO, USA.
authors.forename: Corey D
authors.initials: CD
authors.lastname: Broeckling
authors.affiliation: Proteomics and Metabolomics Facility, Colorado State University, Fort Collins, CO, USA.
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Prenni
authors.affiliation: MTM Research Centre, School of Science and Technology, Örebro University, Örebro, Sweden.
authors.forename: Bert
authors.initials: B
authors.lastname: van Bavel
authors.affiliation: Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: P Monica
authors.initials: PM
authors.lastname: Lind
authors.affiliation: 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.
authors.forename: Erik
authors.initials: E
authors.lastname: Ingelsson
authors.affiliation: Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Lind
mesh_terms: D000368:Aged; D003633:Dichlorodiphenyl Dichloroethylene / Q000097:blood*; D004785:Environmental Pollutants / Q000097:blood*; D005260:Female; D006581:Hexachlorobenzene / Q000097:blood*; D006801:Humans; D050356:Lipid Metabolism / Q000502:physiology*; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010575:Pesticides / Q000097:blood*; D011446:Prospective Studies; D013548:Sweden
chemical_list: D004785:Environmental Pollutants; D008055:Lipids; D010575:Pesticides; D003633:Dichlorodiphenyl Dichloroethylene; D006581:Hexachlorobenzene
keywords: DDT; HCB; Human exposure; Metabolic effects; Metabolomics; Organochlorine pesticides