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Effect of Mixture of Heavy Metals on Metabolic Syndrome and Its Components in Individuals ≥ 18 Years of Age: From Big Data to Molecular Mechanisms Involved

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Abstract

Scarce information exists about the link between mixed heavy metals and metabolic syndrome (MetS) and its components, as well as its molecular mechanism. Thus, we identified the associations of serum cadmium, lead, and mercury with MetS and its components using linear regression models, weighted quantile sum (WQS) regression, quantile g-computation (qgcomp), and Bayesian kernel machine regression (BKMR). Of the 5581 subjects included, 30.8% had MetS. In the logistic regression model, serum mercury was associated with MetS and its components, and significant trends were observed for these heavy metal quantiles (p < 0.001). Serum mercury levels were also linked with MetS and its components in the WQS and qgcomp models. In BKMR analysis, the overall effect of the mixture was significantly associated with MetS and its components. Serum mercury showed positive trends and was observed as the most important factor associated with MetS, along with elevated waist circumference and elevated blood pressure. In in-silico toxicogenomic data mining, we found several pathways (insulin resistance, IL6 signaling pathway, and adipogenesis), regulation of lipid localization, and metabolic syndrome X as key molecular mechanisms that may be affected by heavy metals and involved in the development of MetS. We identified hsa-miR-124-3p as the highest interaction and expression implicated in the MetS process. We also used miRNAsong to create and test a miRNA sponge sequence for these miRNAs, which may be promising for being used in MetS therapy. In particular, the cutoff levels for exposure levels related to MetS and its components were also reported.

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Data Availability

Data from KNHANES is available online at https://knhanes.kdca.go.kr/knhanes/main.do.

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Acknowledgements

The authors are grateful to all research staff for their excellent contributions in data collection in the survey.

Funding

This study supported by National Research Foundation of Korea (NRF) (Grant No. 2022R1A2C1005643).

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Authors and Affiliations

  1. Department of Pharmacy, College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, Sunchon, Jeonnam, 57922, Republic of Korea

    Hai Duc Nguyen, Hojin Oh & Min-Sun Kim

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  1. Hai Duc Nguyen
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  2. Hojin Oh
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HDN: Conceptualization, methodology, formal analysis, investigation, resources, data curation, writing—original draft, writing—review & editing, visualization. MSK: visualization.

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Before investigations, all participants in KNHANES provided written informed consent, which was carried out by the Health and Nutrition Examination Department of the Korea Centers for Disease Control and Prevention. This study was approved by the KNHANES inquiry commission (IRB Approval numbers: 2009-01CON-03-2C, 2010-02CON-21-C, 2011-02CON-06-C, 2012-01EXP-01-2C, 2013-07CON-03-4C, 2013-12EXP-03-5C). From 2016 to 2017, KNHANES was exempt from review regarding research ethics under the Bioethics and Safety Act.

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Nguyen, H.D., Oh, H. & Kim, MS. Effect of Mixture of Heavy Metals on Metabolic Syndrome and Its Components in Individuals ≥ 18 Years of Age: From Big Data to Molecular Mechanisms Involved. Expo Health 15, 773–805 (2023). https://doi.org/10.1007/s12403-022-00523-y

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