Isomeric lipid signatures reveal compartmentalized fatty acid metabolism in cancer.

Young, Reuben S E; Bowman, Andrew P; Tousignant, Kaylyn D; Poad, Berwyck L J; Gunter, Jennifer H; Philp, Lisa K; Nelson, Colleen C; Ellis, Shane R; Heeren, Ron M A; Sadowski, Martin C; Blanksby, Stephen J (2022). Isomeric lipid signatures reveal compartmentalized fatty acid metabolism in cancer. Journal of lipid research, 63(6), p. 100223. American Society for Biochemistry and Molecular Biology ASBMB 10.1016/j.jlr.2022.100223

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The cellular energy and biomass demands of cancer drive a complex dynamic between uptake of extracellular fatty acids (FA) 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, labelled FA uptake also disrupted canonical isomer patterns of the unlabeled lipidome, and induced repartitioning of n-3 and n-6 polyunsaturated FAs 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Sadowski, Martin

ISSN:

0022-2275

Publisher:

American Society for Biochemistry and Molecular Biology ASBMB

Language:

English

Submitter:

Pubmed Import

Date Deposited:

11 May 2022 11:34

Last Modified:

29 Jun 2022 00:14

Publisher DOI:

10.1016/j.jlr.2022.100223

PubMed ID:

35537528

Uncontrolled Keywords:

Fatty acid/Transport Imaging Mass Spectrometry Lipase Lipid Isomers Lipolysis and fatty acid metabolism Ozone-Induced Dissociation Phospholipid/Metabolism Phospholipids/Phosphatidylcholine Stable-Isotope Tracing

BORIS DOI:

10.48350/169906

URI:

https://boris.unibe.ch/id/eprint/169906

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