Omega-3 Fatty Acid Intake and Oxylipin Production in Response to Short-Term Ambient Air Pollution Exposure in Healthy Adults

Oxylipins are specialized lipid mediators that can have dual functions, either promoting inflammation or supporting resolution. Exposure to air pollution is associated with systemic inflammation that may be modified by oxylipins derived from polyunsaturated fatty acids (FA). In this study, we examined whether short-term air pollution exposure is associated with changes in circulating oxylipins in healthy adults, who were on high- or low-dietary omega-3 fatty acid (n-3 FA) intakes. We measured 56 oxylipin species from participants' plasma samples and employed mixed-effects models to assess the associations, stratified by n-3 FA groups. Plasma concentrations of oxylipins derived from n-3 FA [e.g., 14-hydroxydocosahexaenoic acid (14-HDHA) & 11-hydroxydocosahexaenoic acid (11-HDoHE), and 12-hydroxyeicosapentaenoic acid (12-HEPE)] were significantly higher in the high n-3 FA group compared to the low group. Conversely, selected oxylipins derived from n-6 FA [e.g., 15-hydroxyeicosatetraenoic acid (15-HETE) and 14,15-Dihydroxyeicosatrienoic acid (14,15-DiHETrE)] were significantly lower in the high n-3 group. Exposure to PM_2.5, O₃, and NO₂ was associated with reductions in pro-inflammatory oxylipins produced by lipoxygenase in the high n-3 FA group, but not in the low group; for example, 12-HETE. Furthermore, participants in the high n-3 group exposed to PM_2.5, O₃, and NO₂ had elevated levels of n-3 FA-derived pro-resolving oxylipins compared to those in the low n-3 group; for instance, 12-HEPE and 14-HDHA & 11-HDoHE. In conclusion, short-term air pollution exposure was associated with lower pro-inflammatory and higher pro-resolving oxylipin levels in the high n-3 FA group. These findings suggest n-3-derived lipid metabolites may promote inflammation resolution induced by air pollution.