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Metal mixtures with longitudinal changes in lipid profiles: findings from the manganese-exposed workers healthy cohort

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Abstract

The majority of epidemiological investigations on metal exposures and lipid metabolism employed cross-sectional designs and focused on individual metal. We explored the associations between metal mixture exposures and longitudinal changes in lipid profiles and potential sexual heterogeneity. We recruited 250 men and 73 women, aged 40 years at baseline (2012), and followed them up in 2020, from the manganese-exposed workers healthy cohort. We detected metal concentrations of blood cells at baseline with inductively coupled plasma mass spectrometry. Lipid profiles were repeatedly measured over 8 years of follow-up. We performed sparse partial least squares (sPLS) model to evaluate multi-pollutant associations. Bayesian kernel machine regression was utilized for metal mixtures as well as evaluating their joint impacts on lipid changes. In sPLS models, a positive association was found between manganese and change in total cholesterol (TC) (beta = 0.169), while a negative association was observed between cobalt (beta =  − 0.134) and change in low density lipoprotein cholesterol (LDL-C) (beta =  − 0.178) among overall participants, which were consistent in men. Interestingly, rubidium was positively associated with change in LDL-C (beta = 0.273) in women, while copper was negatively associated with change in TC (beta =  − 0.359) and LDL-C (beta =  − 0.267). Magnesium was negatively associated with change in TC (beta =  − 0.327). We did not observe the significantly cumulative effect of metal mixtures on lipid changes. In comparison to other metals, manganese had a more significant influence on lipid change [group PIP (0.579) and conditional PIP (0.556) for TC change in men]. Furthermore, male rats exposed to manganese (20 mg/kg) had higher levels of LDL-C in plasma and more apparent inflammatory infiltration, vacuolation of liver cells, nuclear pyknosis, and fatty change than the controls. These findings highlight the potential role of metal mixtures in lipid metabolism with sex-dependent heterogeneity. More researches are needed to explore the underlying mechanisms.

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Data availability

The datasets used or analyzed and materials during the current study are available from the corresponding author on reasonable request.

Abbreviations

MEWHC:

Manganese-exposed workers healthy cohort

ICP-MS:

Inductively coupled plasma mass spectrometry

sPLS:

Sparse partial least squares

BKMR:

Bayesian kernel machine regression

TC:

Total cholesterol

TG:

Triglycerides

HDL-C:

High-density lipoprotein cholesterol

LDL-C:

Low-density lipoprotein cholesterol

LOD:

Limit of detection

ICC:

Intraclass correlation coefficient

BMI:

Body mass index

OLS:

Ordinary least squares

PIP:

Posterior inclusion probabilities

Mg:

Magnesium

Mn:

Manganese

Fe:

Iron

Co:

Cobalt

Cu:

Copper

Zn:

Zinc

Se:

Selenium

Rb:

Rubidium

Cd:

Cadmium

Pb:

Lead

ROS:

Reactive oxygen species

SHBG:

Sex hormone-binding globulin

ERRα:

Estrogen-related receptor alpha

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Acknowledgements

We would like to thank all participants who volunteered to take part in this study and all researchers involved in the project.

Funding

This work was funded by the National Natural Science Foundation of China (U21A20340, 82073504) and Guangxi Natural Science Fund for Innovation Research Team (2017GXNSFGA198003).

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Author notes

  1. Xiaoting Ge, Guohong Ye, and Junxiu He contributed equally to this article.

Authors and Affiliations

  1. Department of Public Health, School of Medicine, Guangxi University of Science and Technology, Liuzhou, 545006, China

    Xiaoting Ge & Xiaobo Yang

  2. Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, 530021, China

    Xiaoting Ge, Guohong Ye, Junxiu He, Yu Bao, Yuan Zheng, Hong Cheng, Xiuming Feng, Wenjun Yang, Fei Wang & Xiaobo Yang

  3. Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning, 530021, China

    Yunfeng Zou

  4. Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, 530021, China

    Yunfeng Zou & Xiaobo Yang

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  1. Xiaoting Ge
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Contributions

Xiaoting Ge: Writing, original draft; writing, review and editing. Guohong Ye: Writing, original draft; writing, review and editing. Junxiu He: Conceptualization, writing—review and editing. Yu Bao: Investigation, data curation. Yuan Zheng: Investigation, data curation. Hong Cheng: Methodology. Xiuming Feng: Investigation, data curation. Wenjun Yang: Investigation, data curation. Fei Wang: Writing—review and editing. Yunfeng Zou: Conceptualization. Xiaobo Yang: Supervision, project administration.

Corresponding author

Correspondence to Xiaobo Yang.

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The Medical Ethics Committee of Guangxi Medical University (ID: 20200021) have approved all study procedures.

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The authors declare no competing interests.

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Ge, X., Ye, G., He, J. et al. Metal mixtures with longitudinal changes in lipid profiles: findings from the manganese-exposed workers healthy cohort. Environ Sci Pollut Res 29, 85103–85113 (2022). https://doi.org/10.1007/s11356-022-21653-5

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