Fine particulate matter (PM2.5)-induced pulmonary oxidative stress contributes to changes in the plasma lipidome and liver transcriptome in mice.

Fine particulate matter (PM2.5) air pollution exposure increases the cardiovascular disease risk. Although the specific mechanisms remain elusive, it is thought that PM2.5-induced oxidative stress and endothelial dysfunction contribute to this pathogenesis. Our previous findings indicate that PM2.5 impairs vascular health via a circulating factor and that plasma lipid changes contribute to the observed vascular effects. In the current study, we extend on these findings by further characterizing PM2.5-induced changes in circulating lipids and examining whether the observed changes were accompanied by related alterations in the liver transcriptome. To address the role of pulmonary oxidative stress, we exposed wild-type (WT) mice and mice that overexpress extracellular superoxide dismutase (ecSOD-Tg) in the lungs to concentrated ambient PM2.5 (CAP, 9 days). We found that CAP decreased circulating complex lipids and increased free fatty acids and acylcarnitines in WT, but not ecSOD-Tg mice. These plasma lipid changes were accompanied by transcriptional changes in genes that regulate lipid metabolism (eg, upregulation of lipid biosynthesis, downregulation of mitochondrial/peroxisomal FA metabolism) in the liver. The CAP-induced changes in lipid homeostasis and liver transcriptome were accompanied by pulmonary but not hepatic oxidative stress and were largely absent in ecSOD-Tg mice. Our results suggest that PM2.5 impacts hepatic lipid metabolism; however, it remains unclear whether the transcriptional changes in the liver contribute to PM2.5-induced changes in plasma lipids. Regardless, PM2.5-induced changes in the plasma lipidome and hepatic transcriptome are, at least in part, mediated by pulmonary oxidative stress.