Abstract
BackgroundCaloric 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.ResultsMale C57BL/6 J 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.ConclusionThese 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.
Highlights
Ambient particulate matter (PM) pollution is among the leading four risk factors contributing to deaths and disability-adjusted life-years (DALYs) in China [1]
Characteristics of Caloric restriction (CR)-diet fed mice In order to adapt to a state of calorie restriction (CR), we gave mice a specific diet to progressively achieve a 40% reduction of calorie intake as described in Method section (Fig. S1)
Compared with ad libitum (AL)-fed mice, CR led to a reduction in body weight (BW) by 20.22 ~ 21.05% (P < 0.05) (Fig. 1ab), in subcutaneous adipose tissue (SAT) by 23.30 ~ 32.20% (P < 0.05) (Fig. 1c), and in visceral adipose tissue (VAT) by 43.39 ~ 44.32% (P < 0.05) (Fig. 1d)
Summary
Ambient particulate matter (PM) pollution is among the leading four risk factors contributing to deaths and disability-adjusted life-years (DALYs) in China [1]. Intervention modalities are urgently required against the development of diseases associated with PM exposure Both epidemiologic and clinical investigations have established strong evidence that dietary modifications, nutrition, and lifestyle have an impact on the onset of diseases associated with environmental toxic insults [10,11,12]. High fat diet or high caloric intake can alter the biological and metabolic activity of individuals, leading to oxidative damage, inflammation and insulin resistance, all of which increase the health risk associated with environmental exposures [16, 17]. We have posited that modifying dietary habits or nutrient intake would represent a novel approach to protect human beings from health impairment associated with air pollution. The effects of CR on adverse health outcomes in response to particulate matter (PM) exposure and the underlying mechanisms have yet to be defined
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