Wildfire smoke induces GM3 ganglioside lipid accumulation and transcriptomic shifts in mouse lung tissue: A smoke signal story.

Wildfire smoke is a growing concern due to continually rising exposures and links to numerous adverse health effects. Lipids are essential regulators of cellular health, yet their changes from wildfire smoke remain uncharacterized. To investigate molecular alterations driven by smoke inhalation, a lipidomic analysis of lung tissue from mice exposed to various wildfire simulations was performed. Smoke condensates were generated from three biomasses (pine needle, pine core, and eucalyptus) combusted under flaming (640 °C) and smoldering (500 °C) conditions. Six mouse groups were subjected to the different smoke condensate exposures, in addition to saline and lipopolysaccharide negative and positive control groups. Lung tissues were collected 4 h post-exposure and analyzed using a multidimensional platform coupling liquid chromatography, ion mobility spectrometry, and mass spectrometry. A total of 355 unique lipids were identified. Statistical comparisons between each wildfire condition and negative controls revealed 4-7 significantly altered lipids per condition (p < 0.05 and logFC| ≥ 1). Notably, all exposures resulted in an increased abundance of monosialodihexosylgangliosides (GM3s), the structurally simplest type of ganglioside. GM3 enrichment contributes to the formation of specialized microdomains including caveolae and lipid rafts, which can alter cell function regulation. Thus, to understand influenced molecular pathways, transcriptomic signatures from the same samples were evaluated. Here, differential expression was observed for genes involved in ganglioside metabolism, biosynthesis, and those regulated by gangliosides. These findings demonstrate concurrent changes across the transcriptome and lipidome in response to biomass smoke with many differentially expressed genes also implicated in inflammation and cancer, highlighting potential downstream effects of exposure.