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Published on: February 15, 2021
Bisphenol A exposure impairs cardiometabolic health: Integrative human evidence and zebrafish heart multi-omics
Xiangbin Liu1, Jun Yi2, Zhenyu Li3
1Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha 410013, China.
Objective:
Bisphenol A (BPA) is a widely used endocrine-disrupting chemical potentially linked to cardiometabolic disorders. However, the association between BPA exposure and cardiometabolic index (CMI), as well as the underlying cardiac molecular mechanisms, remains insufficiently understood. This study aimed to investigate the associations between BPA exposure and CMI in humans, and to explore direct cardiac effects and underlying molecular mechanisms in a zebrafish model.
Methods:
Data from 844 participants in the NHANES survey were analyzed to assess associations between BPA and CMI, including stratified analyses and mediation analyses of inflammatory biomarkers. In parallel, zebrafish were exposed to BPA, and cardiac injury was evaluated using histopathology, RNA sequencing, and untargeted metabolomics.
Results:
In NHANES, BPA was positively associated with CMI (β = 0.12, 95% CI: 0.00-0.25, P = 0.049). The association was stronger in participants aged 21-39 years (β = 0.17, 95% CI: 0.06-0.27, P = 0.009) and in non-Hispanic Whites (β = 0.14, 95% CI: 0.01-0.26, P = 0.033). Mediation analysis indicated that C-reactive protein accounted for 30.11% and albumin for 11.79% of the total effect. In zebrafish, BPA exposure induced cardiac histopathological abnormalities, including disorganized myocardial fibers and inflammatory infiltration, without gross morphological changes. RNA-seq identified 380 differentially expressed genes, which were enriched in metabolic, signaling, and immune pathways. Metabolomics revealed 83 altered metabolites after annotation from combined positive and negative ionization modes, with downregulation of 5-HETE and upregulation of steroid- and terpenoid-related metabolites, indicating disruption of lipid mediator and steroid metabolism.
Conclusions:
BPA exposure is associated with elevated CMI in humans, with partial mediation by systemic inflammation. In zebrafish, BPA directly induces cardiac transcriptional and metabolic reprogramming, particularly affecting lipid and steroid pathways. These findings provide mechanistic insights into the link between BPA and cardiometabolic risk.
Insights
Bisphenol A (BPA) exposure is linked to higher cardiometabolic index (CMI) in humans, partly due to inflammation. Zebrafish studies show BPA directly harms heart function by altering gene and metabolic pathways, particularly in lipids and steroids.
Area of Science:
- Environmental Health
- Toxicology
- Cardiology
Background:
- Bisphenol A (BPA) is an endocrine-disrupting chemical with suspected links to cardiometabolic disorders.
- The precise relationship between BPA exposure and cardiometabolic index (CMI), and its cardiac molecular effects, require further elucidation.
Purpose of the Study:
- To investigate the association between BPA exposure and CMI in a human population.
- To explore the direct cardiac effects and molecular mechanisms of BPA using a zebrafish model.
Main Methods:
- Analysis of 844 NHANES participants to assess BPA-CMI associations, including mediation by inflammatory biomarkers.
- Zebrafish exposed to BPA, with cardiac injury assessed via histopathology, RNA sequencing, and metabolomics.
Main Results:
- BPA exposure showed a positive association with CMI in NHANES participants (β = 0.12, P = 0.049), particularly in younger adults and non-Hispanic Whites.
- Inflammatory markers like C-reactive protein and albumin partially mediated this association.
- Zebrafish exposed to BPA exhibited cardiac histopathological changes and significant alterations in gene expression (380 genes) and metabolite profiles (83 metabolites), impacting lipid and steroid metabolism.
Conclusions:
- BPA exposure is associated with increased CMI in humans, with systemic inflammation playing a mediating role.
- BPA directly induces cardiac transcriptional and metabolic reprogramming in zebrafish, highlighting potential direct cardiotoxic effects.
- These findings offer mechanistic insights into the link between BPA exposure and cardiometabolic risk.
