Effects of PM and high-fat diet interaction on blood glucose metabolism in adolescent male Wistar rats: A serum metabolomics analysis based on ultra-high performance liquid chromatography/mass spectrometry.

Fine particulate matter (PM) and high-fat diet (HFD) are known to contribute to blood glucose metabolic disorders. However, limited research has investigated the combined impact of PM and HFD on blood glucose metabolism. This study aimed to explore the joint effects of PM and HFD on blood glucose metabolism in rats using serum metabolomics and to identify involved metabolites and metabolic pathways. The 32 male Wistar rats were exposed to filtered air (FA) or PM (real-world inhaled, concentrated PM, 8 times the ambient level, ranging from 131.42 to 773.44 μg/m) and fed normal diet (ND) or HFD for 8 weeks. The rats were divided into four groups (n = 8/group): ND-FA, ND-PM, HFD-FA and HFD-PM groups. Blood samples were collected to determine fasting glucose (FBG), plasma insulin and glucose tolerance test and HOMA Insulin Resistance (HOMA-IR) index was calculated. Finally, the serum metabolism of rats was analyzed by ultra-high performance liquid chromatography/mass spectrometry (UHPLC-MS). Then we constructed the partial least squares discriminant analysis (PLS-DA) model to screen the differential metabolites, and performed pathway analysis to screen the main metabolic pathways. Results showed that combined effect of PM and HFD caused changes in glucose tolerance, increased FBG levels and HOMA-IR in rats and there were interactions between PM and HFD in FBG and insulin. By metabonomic analysis, the serum differential metabolites pregnenolone and progesterone, which involved in steroid hormone biosynthesis, were two different metabolites in the ND groups. In the HFD groups, the serum differential metabolites were L-tyrosine and phosphorylcholine, which involved in glycerophospholipid metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis. When PM and HFD coexist, they may lead to more severe and complex effects on glucose metabolism by affecting lipid metabolism and amino acid metabolism. Therefore, reducing PM exposure and controlling dietary structure are important measures for preventing and reducing glucose metabolism disorders.