Metabolomic and redox alterations in liver cells exposed to biomass burning pollution mixture differ by fatty acids-induced NAFLD

Biomass burning (BB), a significant source of atmospheric pollutants, produces wood tar (WT) particulates, composing a considerable portion of carbonaceous aerosols that pose health risks. Among these health risks is nonalcoholic fatty liver disease (NAFLD), a widely spread condition worldwide. This study uses untargeted metabolomics and functional assays to investigate how pre-existing metabolic conditions, modeled as NAFLD, influence liver cell responses to BB exposure. Human HepG2 cells were pre-incubated with either lauric acid (LA), a saturated fatty acid (FA), or oleic acid (OA), an unsaturated FA, to simulate NAFLD condition before exposure to water-soluble WT (WS-WT), a BB derived mixture. Our findings reveal that OA pre-incubation alters metabolite profiles more significantly than LA pre-incubation alone and that significantly different metabolomic alterations were observed by pretreatment following exposure to WS-WT. Further, OA pre-incubation provides more protective effects against WS-WT exposure than LA. Metabolomic analysis showed that OA-preincubated cells exhibited higher levels of long-chain FA metabolites that are crucial for mitochondrial β-oxidation, suggesting enhanced lipid metabolism and mitochondrial function. In contrast, LA pre-incubation increased mitochondrial dysfunction and susceptibility to WS-WT cytotoxicity, as evidenced by reduced oxygen consumption rate (OCR) levels. Additionally, exposure to WS-WT decreased GSH/GSSG ratio, indicating redox imbalance, particularly in LA-treated cells. This study demonstrates that pre-existing metabolic conditions may influence cellular responses to environmental toxins. They emphasize the need for complementing traditional toxicological assays with omics to identify systemic responses to complex exposure mixtures, and further research into the metabolic pathways and the development of targeted interventions for pollution-associated NAFLD.