PMID- 36822003 OWN - NLM STAT- MEDLINE DCOM- 20230321 LR - 20230322 IS - 1873-6750 (Electronic) IS - 0160-4120 (Linking) VI - 173 DP - 2023 Mar TI - Metabolome-wide association study of four groups of persistent organic pollutants and abnormal blood lipids. PG - 107817 LID - S0160-4120(23)00090-9 [pii] LID - 10.1016/j.envint.2023.107817 [doi] AB - Environmental exposure increases the risk of dyslipidemia, which affects human health. Research has shown that persistent organic pollutants (POPs), including per- and polyfluoroalkyl substances (PFASs), polychlorinated biphenyls, polybrominated diphenyl ethers, and phthalate metabolites, are associated with a higher risk of abnormal blood lipid levels in humans. However, the key molecules involved in dyslipidemia and the mechanisms are not fully understood. This study aims to investigate the biomarkers that mediate the relationships between blood lipids and four groups of POPs and revealed their potential mechanisms. Specifically, in 278 male blood samples, blood lipid and POPs levels were measured and metabolites were detected using untargeted metabolomics. Spearman's correlation analysis and binary logistic regression were employed to assess the relationship between POPs and lipid indexes. We observed that PFASs were associated with a higher risk of abnormal total cholesterol (TC) and low-density lipoprotein (LDL), while other POPs displayed little association with abnormal lipid indexes. Among all the PFASs, 6:2Cl-PFESA was associated with the fewest metabolites. A metabolome-wide association study combined with a meet-in-the-middle approach was used to identify potential biomarkers that mediate the association between POPs and abnormal blood lipids. The mediation analysis pointed to 105 significant mediators as potential biomarkers mediating the association between PFASs and TC, and 82 significant mediators were potential biomarkers that mediated the association between PFASs and LDL. 24-Hydroxycholesterol, 3alpha,7alpha-dihydroxy-5beta-cholestan-26-al, PC(18:0/0:0), PC(22:5/0:0), GPCho(18:1/18:1), LysoPC(22:2(13Z,16Z)), LysoPC(16:0), 9(S)-HODE, 9,10-DHOME, l-glutamate, 4-hydroxybutyric acid, cytosine, PC(14:1(9Z)/18:0), sphinganine, and (S)-beta-aminoisobutyrate were identified as important biomarkers. The mechanism may mainly involves glycerophospholipid metabolism, primary bile acid biosynthesis, and linoleic acid metabolism. PPARgamma likely plays a role in the associations between PFASs and abnormal cholesterol metabolism. Overall, our study provides clues for the early detection of PFAS-induced dyslipidemia and brings forth a theoretical framework for further research into this mechanism. CI - Copyright (c) 2023 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Chen, Yiran AU - Chen Y AD - Guangzhou Center for Disease Control and Prevention, Guangzhou 510440, China; Institute of Public Health, Guangzhou Medical University & Guangzhou Center for Disease Control and Prevention, Guangzhou 510440, China. FAU - Lv, Jiayun AU - Lv J AD - Guangzhou Center for Disease Control and Prevention, Guangzhou 510440, China; Institute of Public Health, Guangzhou Medical University & Guangzhou Center for Disease Control and Prevention, Guangzhou 510440, China. FAU - Fu, Lei AU - Fu L AD - Guangzhou Center for Disease Control and Prevention, Guangzhou 510440, China; Institute of Public Health, Guangzhou Medical University & Guangzhou Center for Disease Control and Prevention, Guangzhou 510440, China. FAU - Wu, Yan AU - Wu Y AD - Guangzhou Center for Disease Control and Prevention, Guangzhou 510440, China; Institute of Public Health, Guangzhou Medical University & Guangzhou Center for Disease Control and Prevention, Guangzhou 510440, China. FAU - Zhou, Si AU - Zhou S AD - Guangzhou Center for Disease Control and Prevention, Guangzhou 510440, China; Institute of Public Health, Guangzhou Medical University & Guangzhou Center for Disease Control and Prevention, Guangzhou 510440, China. FAU - Liu, Shiwei AU - Liu S AD - School of Public Health, China Medical University, Shenyang 110122, China. FAU - Zheng, Linjie AU - Zheng L AD - School of Public Health, Southern Medical University, Guangzhou 510515, China. FAU - Feng, Wenru AU - Feng W AD - Guangzhou Center for Disease Control and Prevention, Guangzhou 510440, China; Institute of Public Health, Guangzhou Medical University & Guangzhou Center for Disease Control and Prevention, Guangzhou 510440, China. FAU - Zhang, Lin AU - Zhang L AD - Guangzhou Center for Disease Control and Prevention, Guangzhou 510440, China. Electronic address: gzcdchwk@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230213 PL - Netherlands TA - Environ Int JT - Environment international JID - 7807270 RN - 0 (Persistent Organic Pollutants) RN - 0 (Fluorocarbons) RN - 0 (Environmental Pollutants) RN - DFC2HB4I0K (Polychlorinated Biphenyls) RN - 0 (Lipids) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Male MH - Humans MH - Persistent Organic Pollutants MH - *Fluorocarbons MH - *Environmental Pollutants/adverse effects MH - *Polychlorinated Biphenyls MH - Lipids MH - Metabolome MH - Cholesterol OTO - NOTNLM OT - Abnormal cholesterol metabolism OT - Metabolomics OT - Per- and polyfluoroalkyl substances OT - Persistent organic pollutants COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/02/24 06:00 MHDA- 2023/03/22 06:00 CRDT- 2023/02/23 18:29 PHST- 2022/12/13 00:00 [received] PHST- 2023/01/18 00:00 [revised] PHST- 2023/02/10 00:00 [accepted] PHST- 2023/02/24 06:00 [pubmed] PHST- 2023/03/22 06:00 [medline] PHST- 2023/02/23 18:29 [entrez] AID - S0160-4120(23)00090-9 [pii] AID - 10.1016/j.envint.2023.107817 [doi] PST - ppublish SO - Environ Int. 2023 Mar;173:107817. doi: 10.1016/j.envint.2023.107817. Epub 2023 Feb 13.