Environmental chemical burden in metabolic tissues and systemic biological pathways in adolescent bariatric surgery patients: A pilot untargeted metabolomic approach

• Type of Material: Article
• Authors: Damaskini Valvi, Icahn School of Medicine at Mount Sinai; Douglas Walker, Emory University; Thomas Inge, Children's Hospital Colorado and University of Colorado; Scott Bartell, Emory University; Todd Jenkins, Cincinnati Children’s Hospital; Michael Helmrath, Cincinnati Children’s Hospital; Thomas Ziegler, Emory University; Michele A La Merrill, University of California Davis; Sandrah P Eckel, University of Southern California; David Conti, University of Southern California; Yongliang Liang, Emory University; Dean Jones, Emory University; Rob McConnell, University of Southern California; Leda Chatzi, University of Southern California
• Language: English
• Date: 2020-10-01
• Publisher: PERGAMON-ELSEVIER SCIENCE LTD
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2020 The Authors. Published by Elsevier Ltd.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.envint.2020.105957
• Title of Journal or Parent Work: ENVIRONMENT INTERNATIONAL
• Volume: 143
• Start Page: 105957
• End Page: 105957
• Grant/Funding Information: This study was supported by the National Institute of Health, the National Institute of Environmental Health Sciences (R21ES028903, R21ES029328, R21ES029681, R01ES029944, R01ES030364, R01ES024946, U2CES026561, U2CES030163, P30ES023515, P30ES019776, P30ES007048, P01ES022845, R01ES024946, R01ES030691), USDA National Institute of Food and Agriculture (Hatch project: 1002182), and the U. S. Environmental Protection Agency (RD-83544101).
• Keywords: Exposome; Liver; Environmental Sciences; Bariatric surgery; PRENATAL EXPOSURE; Life Sciences & Biomedicine; POLYBROMINATED DIPHENYL ETHERS; SUBCUTANEOUS ADIPOSE-TISSUE; DISRUPTING CHEMICALS; Persistent organic pollutants; WEIGHT-LOSS; Environmental Sciences & Ecology; INSULIN; Science & Technology; PERSISTENT ORGANIC POLLUTANTS; Adipose tissue; OBESITY; ORGANOCHLORINE PESTICIDES; High-resolution metabolomics; POLYCHLORINATED-BIPHENYLS

Abstract

Background: Advances in untargeted metabolomic technologies have great potential for insight into adverse metabolic effects underlying exposure to environmental chemicals. However, important challenges need to be addressed, including how biological response corresponds to the environmental chemical burden in different target tissues. Aim: We performed a pilot study using state-of-the-art ultra-high-resolution mass spectrometry (UHRMS) to characterize the burden of lipophilic persistent organic pollutants (POPs) in metabolic tissues and associated alterations in the plasma metabolome. Methods: We studied 11 adolescents with severe obesity at the time of bariatric surgery. We measured 18 POPs that can act as endocrine and metabolic disruptors (i.e. 2 dioxins, 11 organochlorine compounds [OCs] and 5 polybrominated diphenyl ethers [PBDEs]) in visceral and subcutaneous abdominal adipose tissue (vAT and sAT), and liver samples using gas chromatography with UHRMS. Biological pathways were evaluated by measuring the plasma metabolome using high-resolution metabolomics. Network and pathway enrichment analysis assessed correlations between the tissue-specific burden of three frequently detected POPs (i.e. p,p’-dichlorodiphenyldichloroethene [DDE], hexachlorobenzene [HCB] and PBDE-47) and plasma metabolic pathways. Results: Concentrations of 4 OCs and 3 PBDEs were quantifiable in at least one metabolic tissue for > 80% of participants. All POPs had the highest median concentrations in adipose tissue, especially sAT, except for PBDE-154, which had comparable average concentrations across all tissues. Pathway analysis showed high correlations between tissue-specific POPs and metabolic alterations in pathways of amino acid metabolism, lipid and fatty acid metabolism, and carbohydrate metabolism. Conclusions: Most of the measured POPs appear to accumulate preferentially in adipose tissue compared to liver. Findings of plasma metabolic pathways potentially associated with tissue-specific POPs concentrations merit further investigation in larger populations.