학술논문

Isomeric lipid signatures reveal compartmentalized fatty acid metabolism in cancer
Document Type
article
Source
Journal of Lipid Research, Vol 63, Iss 6, Pp 100223- (2022)
Subject
FA/transport
lipolysis and FA metabolism
lipase
phospholipid/metabolism
phospholipids/phosphatidylcholine
lipid isomers
Biochemistry
QD415-436
Language
English
ISSN
0022-2275
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.