Title

Isomeric lipid signatures reveal compartmentalized fatty acid metabolism in cancer

Publication Name

Journal of Lipid Research

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.

Open Access Status

This publication may be available as open access

Volume

63

Issue

6

Article Number

100223

Funding Number

DP190101486

Funding Sponsor

Queensland University of Technology

Share

COinS
 

Link to publisher version (DOI)

http://dx.doi.org/10.1016/j.jlr.2022.100223