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

Abstract

Background: Caloric restriction (CR) is known to improve health and extend life span 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 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 PM 2.5. Compared to AL-fed mice, CR-fed mice attenuated PM-induced pulmonary injury and systemic toxicity characterized by reduction in oxidative stress, DNA damage and inflammation. Analysis of RNA sequencing revealed that several pulmonary pathways involved in production of 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 systemic 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. Keywords: Caloric restriction, particulate matter, pulmonary injury, systemic effects, RNA sequencing, xenobiotic metabolism.