Proinflammatory lipid signals trigger the health effects of air pollution in individuals with prediabetes

Individuals with metabolic disorders exhibit enhanced susceptibility to the cardiovascular health effects of particulate air pollution, but the underlying mechanisms are not yet understood. We aim to assess whether changes in proinflammatory lipid signals are associated with fine particulate matter (PM₂.₅) exposure in individuals with and without prediabetes. A longitudinal panel study was conducted in Beijing, China, and included 120 participants followed up over 589 clinical visits from August 2013 to February 2015. We measured 12 lipids derived from arachidonic acid pathways in blood samples of the participants via targeted lipidomic analyses. Ambient PM₂.₅ concentrations were continuously monitored at a station for associations with the lipids. Among the 120 participants, 110 (mean [SD] age at recruitment, 56.5 [4.2] years; 31 prediabetics) who visited the clinic at least twice over the follow-up period were assigned exposure values of the outdoor residential PM₂.₅ concentrations during the 1–14 days preceding each clinical visit. With an interquartile range increase in the 1-day-lag PM₂.₅ exposure (64.0 μg/m³), the prediabetic group had consistently greater increases in the concentration of arachidonate metabolites derived from the cytochrome P450 (CYP450) pathway (5,6-DHET, 15.8% [95% CI, 3.5–29.7%]; 8,9-DHET, 9.7% [95% CI, 0.6–19.6%]; 11,12-DHET, 8.3% [95% CI, 1.9–15.1%]; 14,15-DHET, 7.4% [95% CI, 0.9–14.4%]; and 20-HETE, 8.9% [95% CI, 1.0–17.5%]), compared with the healthy group. Among CYP450-derived lipids, 14,15-DHET and 20-HETE significantly mediated 8% and 8% of the PM₂.₅-associated increase in white blood cells, 10% and 13% of that in neutrophils, and 20% and 23% of that in monocytes, respectively, in the prediabetic group. In conclusion, proinflammatory lipid signals from CYP450 pathways triggered the health effects of particulate air pollution in individuals with prediabetes, suggesting that targeting lipid metabolism has therapeutic potential to attenuate or prevent the cardiovascular effects of air pollution in susceptible populations.