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Molecular Speciation and Dynamics of Oxidized Triacylglycerols in Lipid Droplets: Mass Spectrometry and Coarse-Grained Simulations
Dariush Mohammadyania, b, c,
Vladimir A. Tyurina, c,
Matthew O’Briend,
Yoel Sadovskyd,
Dmitry I. Gabriloviche,
Judith Klein-Seetharamanf,
Valerian E. Kagana, c
a Departments of Environmental and Occupational Health
b Departments of Bioengineering
c Departments of Center for Free Radical and Antioxidant Health
d Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA, 15219
e The Wistar Institute, Philadelphia, PA, 19104
f Division of Metabolic and Vascular Health, Medical School, University of Warwick, Coventry CV4 7AL, UK
Received 14 May 2014,
Accepted 25 July 2014,
Available online 9 August 2014
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DOI: 10.1016/j.freeradbiomed.2014.07.042
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Abstract
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 – 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. Amongst the many types of oxidized lipids identified, we found that oxidatively-truncated forms and hydroxy-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.
Keywords
Lipid droplet;
Neutral lipids;
Lipid oxidation;
Hypoxia;
Cancer
http://www.sciencedirect.com/science/article/pii/S0891584914003591#MMCvFirst
