Real ambient particulate matter-induced lipid metabolism disorder: Roles of peroxisome proliferators-activated receptor alpha

A growing body of evidence associated particulate matter (PM) exposure with lipid metabolism disorders, yet, the underlying mechanism remains to be elucidated. Among the major lipid metabolism modulators, peroxisome proliferator-activated receptor (PPAR) alpha plays an important role. In the current study, an individually ventilated cage (IVC) system was used to expose C57/B6 mice to real-ambient PM for six weeks, with or without co-treatment of PPAR alpha agonist WY14,643. The general parameters, liver and adipose tissue pathology, serum lipids, metal deposition and lipid profile of liver were assessed. The results indicated that six weeks of real-ambient PM exposure induced dyslipidemia, including increased serum triglycerides (TG) and decreased high density lipoprotein cholesterol (HDL-C) level, along with steatosis in liver, increased size of adipocytes in white adipose tissue (WAT) and whitening of brown adipose tissue (BAT). ICP-MS results indicated increased Cr and As deposition in liver. Lipidomics analysis revealed that glycerophospholipids and cytochrome P450 pathway were most significantly affected by PM exposure. Several lipid metabolism-related genes, including CYP4A14 in liver and UCP1 in BAT were downregulated following PM exposure. WY14,643 treatment alleviated PM-induced dyslipidemia, liver steatosis and whitening of BAT, while enhancing CD36, SLC27A1, CYP4A14 and UCP1 expression. In conclusion, PPAR alpha pathway participates in PM-induced lipid metabolism disorder, PPAR alpha agonist WY14,643 treatment exerted protective effects on PM-induced dyslipidemia, liver steatosis and whitening of BAT, but not on increased adipocyte size of WAT.