Metabolic outcomes and changes in innate immunity induced by diesel exhaust particles airway exposure and high-fat high-sucrose diet

• Published in: Life sciences (1973) 2023-08, Vol.326, p.121794-121794, Article 121794
• Main Authors: Hasegawa, Yuka, Okamura, Takuro, Nakajima, Hanako, Kitagawa, Nobuko, Majima, Saori, Okada, Hiroshi, Senmaru, Takafumi, Ushigome, Emi, Nakanishi, Naoko, Hamaguchi, Masahide, Takano, Hirohisa, Fukui, Michiaki
• Format: Article
• Language: English
• Subjects: Animals; Cytokines - metabolism; Diesel exhaust particles; Glucose intolerance; Immunity, Innate; Inflammation - pathology; Innate immunity; Innate lymphoid cells; Killer Cells, Natural - metabolism; Lung - metabolism; Male; Mice; Non-alcoholic Fatty Liver Disease - chemically induced; Non-alcoholic Fatty Liver Disease - metabolism; Nonalcoholic fatty liver disease; Particulate Matter; Vehicle Emissions - toxicity
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2023.121794

Epidemiological studies have shown that exposure to diesel exhaust particles (DEP) is associated with metabolic diseases. We used mice with nonalcoholic fatty liver disease (NAFLD) caused by a high-fat, high-sucrose diet (HFHSD), which mimics a Western diet, to investigate the mechanism of NAFLD exacerbation via changes in innate immunity in the lungs by airway exposure to DEP. Six-week-old C57BL6/J male mice were fed HFHSD, and DEP was administered endotracheally once a week for eight weeks. The histology, gene expression, innate immunity cells in the lung and liver, and the serum inflammatory cytokine levels, were investigated. Under the HFHSD, DEP increased blood glucose levels, serum lipid levels, and NAFLD activity scores, and also the expression of genes associated with inflammation in the lungs and liver. DEP caused an increase in ILC1s, ILC2s, ILC3s, and M1 macrophages in the lungs and a marked increase in ILC1s, ILC3s, M1 macrophages, and natural killer cells in the liver, while ILC2 levels were not changed. Furthermore, DEP caused high levels of inflammatory cytokines in the serum. Chronic exposure to DEP in HFHSD-fed mice increased inflammatory cells involved in innate immunity in the lungs and raised local inflammatory cytokine levels. This inflammation spread throughout the body, suggesting the association with the progression of NAFLD via increased inflammatory cells involved in innate immunity and inflammatory cytokine levels in the liver. These findings contribute to a better understanding of the role of innate immunity in air pollution-related systemic diseases, especially metabolic diseases. •Airway exposure of DEP worsens glucose tolerance and NAFLD.•DEP exposure alters the number of innate lymphocytes in the lungs and liver.•Innate immunity may play a role in air pollution-related diseases.