Particulate matter ≤2.5μm (PM) air pollution is a leading environmental risk factor contributing disproportionately to the global burden of non-communicable disease. We compared impact of chronic exposure to PM alone, or with light at night exposure (LL) on metabolism. PM induced peripheral insulin resistance, circadian rhythm (CR) dysfunction, and metabolic and brown adipose tissue (BAT) dysfunction, akin to LL (with no additive interaction between PM and LL). Transcriptomic analysis of liver and BAT revealed widespread but unique alterations in CR genes, with evidence for differentially accessible promoters and enhancers of CR genes in response to PM by ATAC-seq. The histone deacetylases 2, 3, and 4 were downregulated with PM exposure, with increased promoter occupancy by the histone acetyltransferase p300 as evidenced by ChIP-seq. These findings suggest a previously unrecognized role of PM in promoting CR disruption and metabolic dysfunction through epigenetic regulation of circadian targets.
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| http://dx.doi.org/10.1016/j.isci.2020.101728 | DOI Listing |
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