Caloric restriction attenuates C57BL/6J mouse lung injury and extra-pulmonary toxicity induced by real ambient particulate matter exposure

Abstract

Background: Caloric restriction (CR) is known to improve health and extend lifespan in human beings. The effects of CR on adverse health outcomes in response to particulate matter (PM) exposure and the underlying mechanisms have yet to be defined.Results: Male C57BL/6J mice were fed with a CR diet or ad libitum (AL) and exposed to PM for 4 weeks in a real-ambient PM exposure system located at Shijiazhuang, China, with a daily mean concentration (95.77 μg/m³) of PM2.5. Compared to AL-fed mice, CR-fed mice showed attenuated PM-induced pulmonary injury and extra-pulmonary toxicity characterized by reduction in oxidative stress, DNA damage and inflammation. RNA sequence analysis revealed that several pulmonary pathways that were involved in production of reactive oxygen species (ROS), cytokine production, and inflammatory cell activation were inactivated, while those mediating antioxidant generation and DNA repair were activated in CR-fed mice upon PM exposure. In addition, transcriptome analysis of murine livers revealed that CR led to induction of xenobiotic metabolism and detoxification pathways, corroborated by increased levels of urinary metabolites of polycyclic aromatic hydrocarbons (PAHs) and decreased cytotoxicity measured in an ex vivo assay.Conclusion: These novel results demonstrate, for the first time, that CR in mice confers resistance against pulmonary injuries and extra-pulmonary toxicity induced by PM exposure. CR led to activation of xenobiotic metabolism and enhanced detoxification of PM-bound chemicals. These findings provide evidence that dietary intervention may afford therapeutic means to reduce the health risk associated with PM exposure.

Inflammation, ageing and diseases of the lung: Potential therapeutic strategies from shared biological pathways

“…Dietary restriction has been shown to increase life span in several models with this mechanism also evolutionarily conserved (Lang et al, 2019). In murine models of lung disease, mice on restricted calorie diet were recently shown to be protected from pulmonary injury and inflammation when exposed to particulate matter (Li, Chen, et al, 2020). Targeting the nutrient sensing mTOR pathway has been shown to reduce pulmonary fibrosis in mice with evidence of a reduction in lung collagen (characteristic of fibrosis) (Korfhagen et al, 2009), and in vitro a reduction in senescence-associated, pro-inflammatory markers in primary endothelial and smooth muscle cells taken from COPD patients (Houssaini et al, 2018).…”