Isomeric lipid signatures reveal compartmentalized fatty acid metabolism in cancer

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

doi:10.1016/j.jlr.2022.100223

Isomeric lipid signatures reveal compartmentalized fatty acid metabolism in cancer

J Lipid Res. 2022 Jun;63(6):100223. doi: 10.1016/j.jlr.2022.100223. Epub 2022 May 7.

Affiliations

¹ School of Chemistry and Physics, Queensland University of Technology, Brisbane, Queensland, Australia; Central Analytical Research Facility (CARF), Queensland University of Technology, Brisbane, Queensland, Australia.
² The Maastricht MultiModal Molecular Imaging Institute (M4I), Division of Imaging Mass Spectrometry, Maastricht University, Maastricht, The Netherlands.
³ Australian Prostate Cancer Research Centre - Queensland (APCRC-Q), School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Princess Alexandra Hospital, Translational Research Institute (TRI), Brisbane, Queensland, Australia.
⁴ The Maastricht MultiModal Molecular Imaging Institute (M4I), Division of Imaging Mass Spectrometry, Maastricht University, Maastricht, The Netherlands; Molecular Horizons and School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, New South Wales, Australia; Illawarra Health and Medical Research Institute (IHMRI), Univeristy of Wollongong, Wollongong, New South Wales, Australia.
⁵ Australian Prostate Cancer Research Centre - Queensland (APCRC-Q), School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Princess Alexandra Hospital, Translational Research Institute (TRI), Brisbane, Queensland, Australia; Institute of Pathology, University of Bern, Bern, Switzerland. Electronic address: martin.sadowski@pathology.unibe.ch.
⁶ School of Chemistry and Physics, Queensland University of Technology, Brisbane, Queensland, Australia; Central Analytical Research Facility (CARF), Queensland University of Technology, Brisbane, Queensland, Australia. Electronic address: stephen.blanksby@qut.edu.au.

Abstract

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

Keywords: FA/transport; imaging MS; lipase; lipid isomers; lipolysis and FA metabolism; ozone-induced dissociation; phospholipid/metabolism; phospholipids/phosphatidylcholine; stable-isotope tracing.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Fatty Acids* / metabolism
Glycerophospholipids / chemistry
Lipid Metabolism
Neoplasms*
Signal Transduction

Substances

Fatty Acids
Glycerophospholipids