Abstract
Epidemiological studies have demonstrated the association between exposure to fine particulate matter (PM2.5) and the onset of non-alcoholic fatty liver disease (NAFLD). However, the potential biological mechanism is largely unknown. Our study was aimed to explore the impact of PM2.5 on the transcriptome level in the liver of ob/ob mice by atmosphere PM2.5 whole-body dynamic exposure system, and meanwhile preliminarily investigated the effects of metformin intervention in this process. More than three thousand differentially expressed genes (DEGs) was screened out by microarray analysis (p < 0.05, |FC|> 1.5). KEGG pathway enrichment analysis showed that these DEGs were mainly enriched in cancers, infectious diseases, and signal transduction, and the most significant pathways were thyroid hormone signaling pathway, chronic myeloid leukemia and metabolic pathways. Then, 12 hub genes were gained through weighted gene correlation network analysis (WGCNA) and verified by qRT-PCR. The expression of 5 genes in darkslateblue module (cd53, fcer1g, cd68, ctss, laptm5) increased after PM2.5 exposure and decreased after metformin intervention. They were related to insulin resistance, glucose and lipid metabolism and other liver metabolism, and also neurodegenerative diseases. This study provided valuable clues and possible protective measures to the liver damage in ob/ob mice caused by PM2.5 exposure, and further research is needed to explore the related mechanism in detail.
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Data availability
All microarray data is MIAME compliant and the raw data has been deposited in NCBIs Gene Expression Omnibus (NCBIs GEO ID: GSE186900, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE186900).
Abbreviations
- KEGG:
-
Kyoto Encyclopedia of Genes and Genomes
- GO:
-
Gene Onotology
- STC-GO:
-
Series test of cluster of gene ontology
- DEGs:
-
Differentially expressed genes
- WGCNA:
-
Weighted correlation network analysis
- qRT-PCR:
-
Real-time quantitative polymerase chain reaction
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Funding
This work was supported by the National Natural Science Foundation of China (91943301, 92043301, 81602876). The authors would like to thank Weiping Tang of Cnkingbio biotechnology Co. Ltd. for bioinformatics assistance.
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LL: writing—first draft, software, visualization, and investigation. LT: writing—first draft, conceptualization, and methodology. TL: visualization and investigation. MS: data curation and investigation. JD: investigation and writing—reviewing and editing. YY: supervision, writing—reviewing and editing. ZS: writing—reviewing and editing.
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This work has received approval for research ethics from the Animal Care and Use Committee of Capital Medical University, which ethical approval number is AEEI-2019–161.
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Highlights
1. Real time exposure of PM2.5 disturbs the transcriptome level in ob/ob mice liver.
2. PM2.5 affects insulin resistance, glucose, and lipid metabolism in obese fatty liver.
3. Metformin could protect the PM2.5-induced metabolic disturbance in obese fatty liver.
4. WGCNA reveals 12 hub genes as potential biomarkers in PM2.5-induced hepatic injury.
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Lin, L., Tian, L., Li, T. et al. Microarray analysis of mRNA expression profiles in liver of ob/ob mice with real-time atmospheric PM2.5 exposure. Environ Sci Pollut Res 29, 76816–76832 (2022). https://doi.org/10.1007/s11356-022-21088-y
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DOI: https://doi.org/10.1007/s11356-022-21088-y