Metabolic effects of air pollution exposure and reversibility
Polluted air is made up of matters smaller than 2.5 µm (PM 2.5) in size. Studies have provided evidence of these matters being responsible for the development of hypertension, insulin resistance (IR), and type 2 diabetes mellitus (T2DM). These conditions are said to be the risk factors for cardiovascular diseases. Many of the other effects of air pollution is unexplored. Rajagopalan and colleagues (2020) conducted a study titled “Metabolic effects of air pollution exposure and reversibility” published in the “Journal of Clinical Investigation”. Summary of the findings can be studied below:
Objective:
To investigate the metabolic phenotypic, transcriptional, and epigenomic changes in response to exposure to concentrated ambient PM2.5
To compare these changes in response to a high-fat diet (HFD)
To study the response of the mentioned parameters in the cessation of exposure.
Method:
Early life exposure was provided to chow-fed C57BL/6J male mice. Exposure of real-world inhaled, concentrated PM2.5 was provided to mice. The exposure was continued for 14 weeks.
Findings:
IR and metabolic dysfunction with air pollution exposure: the phenotype encountered with chronic pollution exposure was specified by alterations in oxygen consumption and EE, hepatic inflammation, elevated triglycerides along with evidence of hepatic steatosis, and glycogen depletion. Surprisingly, no adiposity was observed in mice exposed to pollution. The study put forward a strong sexually dimorphic response as only male mice developed IR.
Differential transcriptome and functional annotation of PM2.5 versus HFD exposure: investigators performed RNA-Seq to quantify transcriptomes using RNA from different tissues and organs. This resulted in the identification of multiple differentially expressed genes (DEGs). As compare to PM2.5, HFD appeared to induce large transcriptional changes across all tissue types. PM2.5 transcriptome was found to be related to cancer progression, cardiometabolic function, and circadian rhythm, and the corresponding pathways associated with these were inflammation, redox stress, metal ion transport, and glucose metabolism. On other hand, an HFD influenced changes in fatty acid biosynthesis, inflammation, gluconeogenesis, and lipid regulatory pathways.
DEGs in insulin-responsive tissue and functional annotations: study reports glycogen depletion due to PM2.5 exposure. In accordance with previous researches, this study also found that pollution is linked to pathways that promote vulnerability to other non-communicable diseases. There are Circadian rhythm alterations that constitute a common denominator for the development of cancer as well as metabolic and cardiovascular diseases.
Changes in chromatin accessibility in response to PM2.5 exposure and an HFD: study reports that environmental exposure leads to epigenetic reprogramming which may represent a critical buffer against an adverse health response caused by the regulation of gene expression and chromosome integrity. Also, there are changes observed in core clock components and transcriptional regulators of the circadian rhythm.
Cessation of PM2.5 exposure leads to reversal of transcriptomic and epigenomic changes: improvement in glucose tolerance and insulin sensitivity was observed when PM2.5 exposure was terminated after 8 weeks. Additionally, reversibility in the circadian gene was also reported suggesting that air pollution exposure causes circadian dysregulation. There was also reversibility observed in chromatin accessibility and of expression of transcripts, notably those involved in insulin action, circadian rhythm, and inflammation.
Limitations:
Investigators acknowledge that study didn’t identify the precise epigenetic regulators that lead to metabolic dysfunction through genome-wide methylation analysis. The authors also acknowledged a well-designed human study to validate these findings.
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