Abstract
BACKGROUND AND AIM: Ambient air pollution (AAP) exposure has been associated with altered blood lipids and liver fat in young adults. MicroRNAs regulate gene expression and may mediate these relationships. This work investigated associations between AAP exposure, serum microRNA networks, lipid profiles, and non-alcoholic fatty liver disease (NAFLD) risk in young adults. METHODS: Participants were 170 young adults (17-22 years) from the Meta-AIR cohort of the Children's Health Study (CHS). Residential AAP exposure (PM(2.5), PM(10), NO(2), 8-hour maximum O(3), redox-weighted oxidative capacity [O(x)(wt)]) was spatially interpolated from monitoring stations via inverse-distance-squared weighting. Fasting serum lipids were assayed. Liver fat was imaged by MRI and NAFLD was defined by ≥ 5.5% hepatic fat fraction. Serum microRNAs were measured via NanoString and microRNA networks were constructed by weighted gene correlation network analysis. The first principal component of each network represented its expression profile. Multivariable mixed effects regression models adjusted for sociodemographic, behavioral, and clinical covariates; baseline CHS town code was a random effect. Effects estimates are scaled to one standard deviation of exposure. Mediation analysis explored microRNA profiles as potential mediators of exposure-outcome associations. DIANA-mirPATH identified overrepresented gene pathways targeted by miRNA networks. RESULTS: Prior-month O(x)(wt) was associated with NAFLD (OR=3.45; p = 0.003) and inversely associated with microRNA Network A (β = -0.016; p = 0.026). Prior-year NO(2) was associated with non-HDL-cholesterol (β = 7.13; p = 0.01) and inversely associated with miRNA Network A (β = -0.019; p = 0.022). Network A expression was inversely associated with NAFLD (OR=0.35; p = 0.010) and non-HDL-C (β = -6.94 mg/dL; p = 0.035). Network A members miR-199a/b-3p and miR-130a, which both target fatty acid synthase, mediated 21% of the association between prior-month O(x)(wt) exposure with NAFLD (p = 0.048) and 23.3% of the association between prior-year NO(2) exposure and non-HDL-cholesterol (p = 0.026), respectively. CONCLUSIONS: Exposure to AAP may contribute to adverse lipid profiles and NAFLD risk among young adults via altered expression of microRNA profiles.