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Liquid Crystal Monomer: A Potential PPARγ Antagonist

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    Ecotoxicology and Public Health

    Liquid Crystal Monomer: A Potential PPARγ Antagonist
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    • Haoduo Zhao
      Haoduo Zhao
      School of Civil and Environmental Engineering, Nanyang Technological University, 639798 Singapore
      Nanyang Environment & Water Research Institute, Nanyang Technological University, 637141 Singapore
      More by Haoduo Zhao
    • Caixia Li
      Caixia Li
      Nanyang Environment & Water Research Institute, Nanyang Technological University, 637141 Singapore
      More by Caixia Li
      Orcidhttps://orcid.org/0000-0003-2190-655X
    • Mihir Yogesh Naik
      Mihir Yogesh Naik
      Lee Kong Chian School of Medicine, Nanyang Technological University, 308232 Singapore
      More by Mihir Yogesh Naik
    • Jia Wu
      Jia Wu
      School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing 210094, China
      More by Jia Wu
    • Angelysia Cardilla
      Angelysia Cardilla
      Lee Kong Chian School of Medicine, Nanyang Technological University, 308232 Singapore
      More by Angelysia Cardilla
    • Min Liu
      Min Liu
      School of Civil and Environmental Engineering, Nanyang Technological University, 639798 Singapore
      Nanyang Environment & Water Research Institute, Nanyang Technological University, 637141 Singapore
      More by Min Liu
    • Fanrong Zhao
      Fanrong Zhao
      Nanyang Environment & Water Research Institute, Nanyang Technological University, 637141 Singapore
      Lee Kong Chian School of Medicine, Nanyang Technological University, 308232 Singapore
      More by Fanrong Zhao
    • Shane Allen Snyder
      Shane Allen Snyder
      School of Civil and Environmental Engineering, Nanyang Technological University, 639798 Singapore
      Nanyang Environment & Water Research Institute, Nanyang Technological University, 637141 Singapore
      More by Shane Allen Snyder
      Orcidhttps://orcid.org/0000-0003-2709-9840
    • Yun Xia*
      Yun Xia
      Lee Kong Chian School of Medicine, Nanyang Technological University, 308232 Singapore
      *Email: [email protected]
      More by Yun Xia
    • Guanyong Su*
      Guanyong Su
      School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing 210094, China
      *Email: [email protected]
      More by Guanyong Su
      Orcidhttps://orcid.org/0000-0003-4356-5194
    • Mingliang Fang*
      Mingliang Fang
      School of Civil and Environmental Engineering, Nanyang Technological University, 639798 Singapore
      Department of Environmental Science and Engineering, Fudan University, Shanghai 200433, China
      *Email: [email protected]
      More by Mingliang Fang
      Orcidhttps://orcid.org/0000-0002-2204-9783
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    Environmental Science & Technology

    Cite this: Environ. Sci. Technol. 2023, 57, 9, 3758–3771
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    https://doi.org/10.1021/acs.est.2c08109
    Published February 23, 2023
    Copyright © 2023 American Chemical Society
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    Abstract

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    Liquid crystal monomers (LCMs) are a large family of artificial ingredients that have been widely used in global liquid crystal display (LCD) industries. As a major constituent in LCDs as well as the end products of e-waste dismantling, LCMs are of growing research interest with regard to their environmental occurrences and biochemical consequences. Many studies have analyzed LCMs in multiple environmental matrices, yet limited research has investigated the toxic effects upon exposure to them. In this study, we combined in silico simulation and in vitro assay validation along with omics integration analysis to achieve a comprehensive toxicity elucidation as well as a systematic mechanism interpretation of LCMs for the first time. Briefly, the high-throughput virtual screen and reporter gene assay revealed that peroxisome proliferator-activated receptor gamma (PPARγ) was significantly antagonized by certain LCMs. Besides, LCMs induced global metabolome and transcriptome dysregulation in HK2 cells. Notably, fatty acid β-oxidation was conspicuously dysregulated, which might be mediated through multiple pathways (IL-17, TNF, and NF-kB), whereas the activation of AMPK and ligand-dependent PPARγ antagonism may play particularly important parts. This study illustrated LCMs as a potential PPARγ antagonist and explored their toxicological mode of action on the trans-omics level, which provided an insightful overview in future chemical risk assessment.

    Copyright © 2023 American Chemical Society

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    Supporting Information

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.est.2c08109.

    • Inverse virtual screening details, reporter gene assay operation, HK2 cell viability assay, HPLC–MS parameters, LCM information, in-house IVS database, LCM ECSR20 for the PPARγ antagonist assay, chemical analysis for exposure verification, heat map of LCM ACID IVS, cytotoxicity test result for selected LCMs, method validation for three reporter gene assays, agonist assay of selected LCMs using the ERα reporter cell line, agonist assay of selected LCMs using the GR reporter cell line, PPARγ assay method validation using synthetic agonist and antagonist, GSEA analysis for HK2 cells exposed to LCM 41, correlation plot of PPAR coactivators, and corepressors’ RNA expression pattern under LCM 41 exposure (PDF)

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    Cited By

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    This article is cited by 37 publications.

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    3. Runhui Yang, Xin Xu, Xinyi Wang, Yumin Niu, Jing Du, Hong Li, Xianggui Chen, Gang Li, Bing Shao. Fluorinated Liquid-Crystal Monomers in Serum from the General Population and Their Impact on Human Health. Environmental Science & Technology 2024, 58 (36) , 15949-15959. https://doi.org/10.1021/acs.est.4c02905
    4. Yuan Liu, Kurunthachalam Kannan. Concentrations, Profiles, and Potential Sources of Liquid Crystal Monomers in Residential Indoor Dust from the United States. Environmental Science & Technology 2024, 58 (28) , 12400-12408. https://doi.org/10.1021/acs.est.4c03131
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    11. Lin Peng, Zenghua Qi, Li Xiang, Wei Wang, Guodong Cao, Yi Ru, Xiaoxiao Wang, Siyi Lin, Zhu Yang, Hong Yan, Zongwei Cai. Fluorinated liquid crystal monomer (FLCM) induces kidney dysfunction by disrupting PPARα-mediated fatty acid oxidation: In vivo, in vitro, and in silico assays. Environmental Chemistry and Ecotoxicology 2025, 7 , 192-200. https://doi.org/10.1016/j.enceco.2024.12.002
    12. Jiawei Cheng, Xiaojuan Li, Yawen Yuan, Mengxiao Wang, Yunsong Mu, Xiaoli Zhao, Fengchang Wu, John P. Giesy. Environmental behavior, toxic potencies, and risks of liquid crystal monomers: A critical review. Critical Reviews in Environmental Science and Technology 2024, 54 (24) , 1902-1919. https://doi.org/10.1080/10643389.2024.2373948
    13. Yulin Wang, Qianqian Jin, Huiju Lin, Xiaotong Xu, Kenneth M.Y. Leung, Kurunthachalam Kannan, Yuhe He. A review of liquid crystal monomers (LCMs) as emerging contaminants: Environmental occurrences, emissions, exposure routes and toxicity. Journal of Hazardous Materials 2024, 480 , 135894. https://doi.org/10.1016/j.jhazmat.2024.135894
    14. Yuan Liu, Kurunthachalam Kannan. Liquid crystal monomers in human, dog and cat feces from the United States. Journal of Hazardous Materials 2024, 480 , 136144. https://doi.org/10.1016/j.jhazmat.2024.136144
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    32. Shan He, Jia He, Siying Ma, Kunyu Wei, Fengchang Wu, Jian Xu, Xiaowei Jin, Yuanhui Zhao, Chris Martyniuk. Liquid Crystal Monomers Disrupt Photoreceptor Patterning of Zebrafish Larvae Via Thyroid Hormone Signaling. 2024https://doi.org/10.2139/ssrn.4765242
    33. YueYue Zhang, Jingjuan Wang, Yuanfei Wu, Xiaojia Huang. One-Pot Fabrication of Task Specific Magnetic Adsorbent for the Efficient Isolation and Capture of Liquid-Crystal Monomers Pollutants. 2024https://doi.org/10.2139/ssrn.4768355
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    36. Jiali Ge, Bibai Du, Mingjie Shen, Zhiqing Feng, Lixi Zeng. A review of liquid crystal monomers: Environmental occurrence, degradation, toxicity, and human exposure of an emerging class of E-waste pollutants. Environmental Pollution 2023, 335 , 122267. https://doi.org/10.1016/j.envpol.2023.122267
    37. Zhipeng Cheng, Shaohan Zhang, Huijun Su, Haoduo Zhao, Guanyong Su, Mingliang Fang, Lei Wang. Emerging organic contaminants of liquid crystal monomers: Environmental occurrence, recycling and removal technologies, toxicities and health risks. Eco-Environment & Health 2023, 2 (3) , 131-141. https://doi.org/10.1016/j.eehl.2023.07.002
    38. Zhiqing Feng, Bibai Du, Mingjie Shen, Xu Han, Xinxin Liang, Lixi Zeng. Nationwide occurrence and distribution of liquid crystal monomers in municipal sewage sludge of China. Science of The Total Environment 2023, 892 , 164453. https://doi.org/10.1016/j.scitotenv.2023.164453
    39. Miao Miao, Xue Wang, Tian Liu, Yan-Jie Li, Wen-Qian Yu, Tong-Mei Yang, Shou-Dong Guo. Targeting PPARs for therapy of atherosclerosis: A review. International Journal of Biological Macromolecules 2023, 242 , 125008. https://doi.org/10.1016/j.ijbiomac.2023.125008
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    Cite this: Environ. Sci. Technol. 2023, 57, 9, 3758–3771
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.est.2c08109
    Published February 23, 2023
    Copyright © 2023 American Chemical Society
    Request reuse permissions

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