Daria M Potashnikova, Anna V Tvorogova, Tatiana N Sotnikova, Alexey A Komissarov, Kirill N Zhuravlev, Aleena A Saidova, Valerya O Makarova, Eugene A Arifulin, Tatiana V Lipina, Olesya M Shirokova, Eugene S Melnikov, Tatiana A Rodina, Anna A Valyaeva, Anastasia A Zharikova, George O Zayratyants, Oleg V Zayratyants, Oleg V Kokorev, Anna Tkachev, Elena A Stekolshchikova, Philipp E Khaitovich, Eugene V Sheval, Leonid B Margolis, Elena J Vasilieva
Pneumonias of diverse etiologies share pronounced lipid deposition accompanied by shifts in lipid metabolism. Integrated imaging and molecular approaches link abnormal lipid deposition to inflammation and highlight lipid metabolic pathways as potential diagnostic and therapeutic targets.
BACKGROUND: Pneumonia is highly prevalent, yet lipid metabolism in the human pneumonic lung remains poorly characterized despite its essential role in pulmonary homeostasis and disease. Here, we report a systematic histological and molecular analysis of lipid deposition in pneumonias of different etiologies.
METHODS: We analyzed fatal COVID-19 and non-COVID-19 pneumonias. Patients underwent ante mortem chest CT and were subsequently examined at autopsy; non-pneumonic autopsy lungs served as controls. Lipid accumulation was visualized on OsO4-postfixed semi-thin sections and Sudan III/Oil Red O cryosections. Lipidomic analysis and fatty acid profiling were performed by chromatography-mass spectrometry. Published bulk and single-cell transcriptomic datasets were re-analyzed and verified by qPCR.
RESULTS: Pneumonic lungs contained frequent intracellular and intravascular lipid droplets, whereas controls showed weak diffuse lipophilic staining. Chest CT indicated increased ante mortem lipid burden in pneumonic lungs, with deposition abundant in inflamed regions and scarce in distal intact areas. Inflamed tissue was enriched in triacylglycerols and unsaturated fatty acids. Transcriptomic re-analysis and qPCR indicated altered pathways of lipid biosynthesis, uptake, and storage across multiple cell populations, particularly macrophages.
CONCLUSIONS: Pneumonias of diverse etiologies share pronounced lipid deposition accompanied by shifts in lipid metabolism. Integrated imaging and molecular approaches link abnormal lipid deposition to inflammation and highlight lipid metabolic pathways as potential diagnostic and therapeutic targets.