Effects of organic chemicals from diesel exhaust particles on adipocytes differentiated from human mesenchymal stem cells

• Published in: Basic & clinical pharmacology & toxicology Vol. 132; no. 1; pp. 83 - 97
• Main Authors: Brinchmann, Bendik C., Holme, Jørn A., Frerker, Nadine, Rambøl, Mia H., Karlsen, Tommy, Brinchmann, Jan E., Kubátová, Alena, Kukowski, Klara, Skuland, Tonje, Øvrevik, Johan
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01-01-2023; John Wiley and Sons Inc
• Subjects: Adipocytes; Adipocytes - chemistry; Adipose tissue; Adrenergic receptors; Air Pollutants - toxicity; air pollution; Animals; Cell differentiation; Chemokines; Combustion; Cytochrome; Cytochrome P450; Cytochromes P450; Diesel; Diesel engines; diesel exhaust particles; Diesel fuels; Exposure; Fossil fuels; Fuel combustion; Gene expression; Genes; Heme oxygenase (decyclizing); Humans; Inflammation; Insulin; Interleukins; Lipophilic; Lipophilicity; Low concentrations; Matrix metalloproteinase; Mesenchymal Stem Cells; Metabolic disorders; metabolic syndrome; Metalloproteinase; Mice; Morbidity; Organic Chemicals; Organic chemistry; Original; Oxidative stress; Oxygenase; PAHs; Particulate emissions; Particulate matter; Particulate Matter - toxicity; Plasminogen activator inhibitors; Receptors (physiology); Stem cell transplantation; Stem cells; Tumors; Vehicle Emissions - toxicity; metabolic syndrome; diesel exhaust particles; inflammation; mesenchymal stem cells; PAHs; air pollution; adipocytes; organic chemicals
• ISSN: 1742-7835; 1742-7843
• DOI: 10.1111/bcpt.13805

Exposure to fine particulate matter (PM2.5) from incomplete fossil fuel combustion (coal, oil, gas and diesel) has been linked to increased morbidity and mortality due to metabolic diseases. PM2.5 exaggerate adipose inflammation and insulin resistance in mice with diet‐induced obesity. Here, we elucidate the hypothesis that such systemic effects may be triggered by adhered particle components affecting adipose tissue directly. Studying adipocytes differentiated from primary human mesenchymal stem cells, we found that lipophilic organic chemicals (OC) from diesel exhaust particles induced inflammation‐associated genes and increased secretion of the chemokine CXLC8/interleukin‐8 as well as matrix metalloprotease 1. The oxidative stress response gene haem oxygenase‐1 and tumour necrosis factor alpha were seemingly not affected, while aryl hydrocarbon receptor‐regulated genes, cytochrome P450 1A1 (CYP1A1) and CYP1B1 and plasminogen activator inhibitor‐2, were clearly up‐regulated. Finally, expression of β‐adrenergic receptor, known to regulate adipocyte homoeostasis, was down‐regulated by exposure to these lipophilic OC. Our results indicate that low concentrations of OC from combustion particles have the potential to modify expression of genes in adipocytes that may be linked to metabolic disease. Further studies on mechanisms linking PM exposure and metabolic diseases are warranted.