Metabolic Pathways Altered by Air Pollution Exposure in Association with Lipid Profiles in Young Adults

Abstract

BACKGROUND AND AIM: Air Pollution is a risk factor for obesity and cardiometabolic diseases in children and adults. We aim to examine the metabolic perturbations associated with air pollution and cardiometabolic health. METHODS: In year 2014 – 2018, we conducted a cross-sectional study assessing lipid profiles (triglycerides, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, very-low-density lipoprotein (VLDL) cholesterol), untargeted serum metabolomics using liquid chromatography-high-resolution mass spectrometry, and one-month and one-year averaged air pollution exposures to NO2, O3, PM2.5 and PM10 at residential addresses among 132 young adults in southern California. A Metabolome-wide association study was conducted to identify metabolomic signatures associated with air pollution exposure. Mummichog pathway enrichment analysis was used to assess altered metabolic pathways, followed by annotations of metabolomic features. Principal component analysis (PCA) of 36 metabolites with confirmed identity was performed to reduce dimensionality and identify clusters. Lastly, regression models were used to analyze the associations of metabolomic PC scores with air pollution and lipid profiles. RESULTS: In total, 4937 and 4372 metabolomic features were detected using HILIC positive and C18 negative modes, with 2047 and 1228 features significantly associated with at least one air pollutant in positive and negative ion mode, respectively (p < 0.05). Metabolic pathways associated with air pollution exposure included fatty acid, glycerophospholid, tryptophan, and tyrosine metabolism. PCA of 48 metabolites involved in the identified pathways indicated that one-month O3, PM10, PM2.5 and one-year NO2 air pollution exposure was positively associated with free fatty acids and oxidative byproducts-related PC score (p < 0.05). This PC score shown to be negatively associated with total cholesterol and LDL cholesterol (p < 0.05). CONCLUSIONS: This study indicated that air pollution exposure is associated with dysregulated fatty acid and lipid metabolism. KEYWORDS: Air Pollution; Metabolomics; Cardiometabolic Health; Lipolysis; Pathway Analysis