Metabolite-Associated Inflammation during Combined Exposure to Cooking Oil Fumes and Atopic Dermatitis: A Multi-Organ Spatial Metabolomics Study

Abstract

How the concurrent impairment of the skin and respiratory barriers is associated with distal-organ injury remains unclear. Here, we integrated untargeted and spatial metabolomics with in situ immunofluorescence to characterize lung-blood-heart-kidney changes in a mouse model of atopic dermatitis (AD) and cooking oil fume (COF) co-exposure. The AD+COF group showed the largest systemic increases in IL-6 and TNF-alpha and the most pronounced changes in circulating and organ metabolites. Succinate accumulation, depletion of xanthine and uric acid, glucose-related perturbations, and spatial lipid remodeling were observed across blood, lungs, heart, and kidneys, and several features were strongly correlated across compartments. These patterns are consistent with coordinated disturbance of tricarboxylic acid cycle-related, pentose phosphate, purine, and membrane-lipid metabolism. Because metabolite tracing, receptor blockade, ATP/ADP measurements, and mitochondrial respiratory assays were not performed, the data do not establish metabolite transport or causal signaling between organs. Instead, they support an association-based cross-organ framework and identify candidate pathways for functional validation. Environmental extrapolation also requires caution because a controlled high-concentration COF regimen was used.