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Environmental Cadmium Exposure Exacerbated Bone Loss in NAFLD Mice

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Abstract

Due to rapid urbanization and industrialization, Cadmium (Cd) contamination is widespread. Meanwhile, the prevalence of nonalcoholic fatty liver disease (NAFLD) has been increasing. Cd is linked to bone damage. However, the osteotoxicity of environmental Cd exposure in NAFLD remains unclear. Therefore, this study aimed to investigate the effects and potential mechanisms of Cd on bone metabolism in NAFLD mice. NAFLD mice were treated with 50 mg/L cadmium chloride in drinking water for 12 weeks. Bone microstructures were scanned by Micro-CT. Liver lipid droplets and fibrosis were measured by histopathological staining. Insulin tolerance tests were performed in mice. RT-PCR and Western blot were performed to analyse hepatic inflammation factors. Results show no damage in healthy mice exposed to Cd. However, Cd exacerbated liver fibrosis and significantly reduced cancellous bone mineral density and decreased the number and thickness of trabecular bone in NAFLD mice. Additionally, the morphology of trabecular bone transformed from a plate structure to a rod structure in NAFLD mice after Cd exposure. The underlying mechanism appears to be related to the Cd-induced direct or indirect toxicity. Exacerbated liver fibrosis, increased inflammatory factors (TGF-β and IL-1β), and reduced lecithin-cholesterol acyltransferase (LCAT) and insulin-like growth factor-1 (IGF-1) might contribute to bone damages. Collectively, our study illustrates that despite lower dosing Cd exposure did not induce bone damages in healthy mice, Cd caused bone loss in NAFLD mice. Therefore, it is recommended that individuals with metabolic disorders should avoid working in Cd pollution environment and consuming cadmium-contaminated food and water.

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Funding

This research was supported by the National Natural Scientific Funding of China (No.81773414) and Postgraduate Research & Practice Innovation Program of Jiangsu Province (SJCX23_1677).

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Authors and Affiliations

  1. School of Public Health, Soochow University, 199 Renai Road, Suzhou, 215123, Jiangsu, China

    Changhao Li, Nana Wang, Yuting Li, Hui Yang, Jiafu Li & Zengli Zhang

Authors
  1. Changhao Li
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  2. Nana Wang
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  3. Yuting Li
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  5. Jiafu Li
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Contributions

Changhao Li and Nana Wang: Writing - Original draft, Conceptualization, Methodology. Yuting Li and Hui Yang: Data curation, Investigation. Jiafu Li: Writing- review and editing. Zengli Zhang: Supervision, Project administration, Writing- review and editing.

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Correspondence to Zengli Zhang.

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The authors declare no competing interests.

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The authors all declare no financial or other potential conflict of interest.

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All animal experiments were conducted in compliance with institutional regulations, and the study protocols were approved by the Institutional Animal Care and Committee of Soochow University (202103A376).

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Li, C., Wang, N., Li, Y. et al. Environmental Cadmium Exposure Exacerbated Bone Loss in NAFLD Mice. Biol Trace Elem Res (2023). https://doi.org/10.1007/s12011-023-04016-0

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