Integrative metabolome and transcriptome profiling reveals discordant energetic stress between mouse strains with differential sensitivity to acrolein-induced acute lung injury

Abstract

Scope: This investigation sought to better understand the metabolic role of the lung and to generate insights into the pathogenesis of acrolein-induced acute lung injury. A respiratory irritant, acrolein is generated by overheating cooking oils or by domestic cooking using biomass fuels, and is in environmental tobacco smoke, a health hazard in the restaurant workplace. Methods and results: Using SM/J (sensitive) and 129X1/SvJ (resistant) inbred mouse strains, the lung metabolome was integrated with the transcriptome profile before and after acrolein exposure. A total of 280 small molecules were identified and mean values (log 2 >0.58 or <-0.58, p<0.05) were considered different for between-strain comparisons or within-strain responses to acrolein treatment. At baseline, 24 small molecules increased and 33 small molecules decreased in the SM/J mouse lung as compared to 129X1/SvJ mouse lung. Notable among the increased compounds was malonylcarnitine. Following acrolein exposure, several molecules indicative of glycolysis and branched chain amino acid metabolism increased similarly in both strains, whereas SM/J mice were less effective in generating metabolites related to fatty acid beta-oxidation. Conclusion: These findings suggest management of energetic stress varies between these strains, and that the ability to evoke auxiliary energy generating pathways rapidly and effectively may be critical in enhancing survival during acute lung injury in mice.