Lipid droplets (LDs) are ubiquitous and physiologically active organelles 
regulating storage and mobilization of lipids in response to metabolic demands. 
Among the constituent LD neutral lipids, such as triacylglycerols, cholesterol 
esters, and free fatty acids, oxidizable polyunsaturated molecular species may 
be quite abundant, yet the structural and functional roles of their oxidation 
products have not been studied. Our previous work documented the presence of 
these peroxidized species in LDs. Assuming that hydrophilic oxygen-containing 
functionalities may markedly change the hydrophobic/hydrophilic molecular 
balance, here we utilized computational modeling to test the hypothesis that 
lipid peroxidation causes redistribution of lipids between the highly 
hydrophobic core and the polar surface (phospho)lipid monolayer-the area 
enriched with integrated enzymatic machinery. Using quantitative liquid 
chromatography/mass spectrometry, we characterized molecular speciation of 
oxTAGs in LDs of dendritic cells in cancer and hypoxic trophoblasts cells as two 
cellular models associated with dyslipidemia. Among the many types of oxidized 
lipids identified, we found that oxidatively truncated forms and hydroxyl 
derivatives of TAGs were the prevailing oxidized lipid species in LDs in both 
cell types. Using coarse-grained molecular dynamics (CG-MD) simulations we 
established that lipid oxidation changed their partitioning whereby oxidized 
lipids migrated into the outer monolayer of the LD, where they can affect 
essential metabolic pathways and undergo conversions, possibly leading to the 
formation of oxygenated lipid mediators.