Isomeric lipid signatures reveal compartmentalized fatty acid metabolism in cancer

• DOI: 10.1016/j.jlr.2022.100223
• Publication Date: 2022-05-07T22:19:31Z
• Authors: Reuben S.E. Young; Andrew P. Bowman; Kaylyn D. Tousignant; Berwyck L.J. Poad; Jennifer H. Gunter; Lisa K. Philp; Colleen C. Nelson; Shane R. Ellis; Ron M.A. Heeren; Martin C. Sadowski; Stephen J. Blanksby
• Keywords: Lipidome; Glycerophospholipids; Glycerophospholipids; Metabolic pathway; De novo synthesis

The cellular energy and biomass demands of cancer drive a complex dynamic between uptake extracellular FAs their de novo synthesis. Given that oxidation synthesized for would result in net-energy loss, there is an implication from these two sources must have distinct metabolic fates; however, hitherto, all been considered part common pool. To probe potential partitioning FAs, cells were supplemented with stable isotope-labeled FAs. Structural analysis the resulting glycerophospholipids revealed labeled largely incorporated to canonical (sn-) positions on glycerol backbone. Surprisingly, FA also disrupted isomer patterns unlabeled lipidome induced repartitioning n-3 n-6 PUFAs into glycerophospholipid classes. These structural changes support existence differences fates derived or demonstrate unique signaling remodeling behaviors usually hidden conventional lipidomics.