Ceramide metabolism mediates the impaired glucose homeostasis following short-term black carbon exposure: A targeted lipidomic analysis

Ambient particulate matter (PM), especially its carbonaceous composition black carbon (BC) increases cardiometabolic risks, yet the underlying mechanisms are incompletely understood. Ceramides (Cer; a class of sphingolipids) are biological intermediates in glucose metabolism.To explore whether Cer metabolism mediates impaired glucose homeostasis following short-term PM exposure.In a panel study in Beijing, China, 112 participants were followed-up between 2016 and 2017. Targeted lipidomic analyses quantified 26 sphingolipids in 387 plasma samples. Ambient BC and PM with aerodynamic diameter ≤ 2.5 μm (PM2.5) were continuously monitored in a station. We examined the associations of sphingolipid levels with average BC and PM2.5 concentrations 1-14 days before clinical visits using linear mixed-effects models, and explored the mediation effects of sphingolipids on PM-associated fasting blood glucose (FBG) difference using mediation analyses.Increased levels of FBG and multiple sphingolipids in Cer metabolic pathways were associated with BC exposure in 1-14-day time window, but not with PM2.5 exposure. For each 10 μg/m3 increase in the average BC concentration 1-14 days before the clinical visits, species in the Cer C24:1 pathway (Cer, dihydroceramide, hexosylceramide, lactosylceramide, and sphingomyelin C24:1) increased in levels ranging from 11.8% (95% confidence interval [CI]: -6.2-33.2) to 48.7% (95% CI: 8.8-103.4), as did the Cer C16:0, C18:0, and C20:0 metabolic pathway species, ranging from 3.2% (95% CI: -5.6-12.9) to 32.4% (95% CI: 7.0-63.8), respectively. The Cer C24:1 metabolic pathway species mediated 6.5-25.5% of the FBG increase associated with BC exposure in 9-day time window. The Cer C16:0, C18:0, and C20:0 metabolic pathway species mediated 5.4-26.2% of the BC-associated FBG difference.In conclusion, Cer metabolism may mediate impaired glucose homeostasis following short-term BC exposure. The current findings are preliminary, which need to be corroborated by further studies.