Isomeric lipid signatures reveal compartmentalized fatty acid metabolism in cancer
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 dis...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-06-01
|
| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227522000566 |
| _version_ | 1811334295019585536 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Reuben S.E. Young |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T17:05:42Z |
| format | Article |
| id | doaj.art-fee2b5d060ce47b7a34577bf15b24534 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-04-13T17:05:42Z |
| publishDate | 2022-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-fee2b5d060ce47b7a34577bf15b245342022-12-22T02:38:29ZengElsevierJournal of Lipid Research0022-22752022-06-01636100223Isomeric lipid signatures reveal compartmentalized fatty acid metabolism in cancerReuben S.E. Young0Andrew P. Bowman1Kaylyn D. Tousignant2Berwyck L.J. Poad3Jennifer H. Gunter4Lisa K. Philp5Colleen C. Nelson6Shane R. Ellis7Ron M.A. Heeren8Martin C. Sadowski9Stephen J. Blanksby10School of Chemistry and Physics, Queensland University of Technology, Brisbane, Queensland, Australia; Central Analytical Research Facility (CARF), Queensland University of Technology, Brisbane, Queensland, AustraliaThe Maastricht MultiModal Molecular Imaging Institute (M4I), Division of Imaging Mass Spectrometry, Maastricht University, Maastricht, The NetherlandsAustralian 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, AustraliaSchool of Chemistry and Physics, Queensland University of Technology, Brisbane, Queensland, Australia; Central Analytical Research Facility (CARF), Queensland University of Technology, Brisbane, Queensland, AustraliaAustralian 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, AustraliaAustralian 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, AustraliaAustralian 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, AustraliaThe 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, AustraliaThe Maastricht MultiModal Molecular Imaging Institute (M4I), Division of Imaging Mass Spectrometry, Maastricht University, Maastricht, The NetherlandsAustralian 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; For correspondence: Stephen J. Blanksby; Martin C. SadowskiSchool of Chemistry and Physics, Queensland University of Technology, Brisbane, Queensland, Australia; Central Analytical Research Facility (CARF), Queensland University of Technology, Brisbane, Queensland, Australia; For correspondence: Stephen J. Blanksby; Martin C. SadowskiThe 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.http://www.sciencedirect.com/science/article/pii/S0022227522000566FA/transportlipolysis and FA metabolismlipasephospholipid/metabolismphospholipids/phosphatidylcholinelipid isomers |
| spellingShingle | 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 Isomeric lipid signatures reveal compartmentalized fatty acid metabolism in cancer Journal of Lipid Research FA/transport lipolysis and FA metabolism lipase phospholipid/metabolism phospholipids/phosphatidylcholine lipid isomers |
| title | Isomeric lipid signatures reveal compartmentalized fatty acid metabolism in cancer |
| title_full | Isomeric lipid signatures reveal compartmentalized fatty acid metabolism in cancer |
| title_fullStr | Isomeric lipid signatures reveal compartmentalized fatty acid metabolism in cancer |
| title_full_unstemmed | Isomeric lipid signatures reveal compartmentalized fatty acid metabolism in cancer |
| title_short | Isomeric lipid signatures reveal compartmentalized fatty acid metabolism in cancer |
| title_sort | isomeric lipid signatures reveal compartmentalized fatty acid metabolism in cancer |
| topic | FA/transport lipolysis and FA metabolism lipase phospholipid/metabolism phospholipids/phosphatidylcholine lipid isomers |
| url | http://www.sciencedirect.com/science/article/pii/S0022227522000566 |
| work_keys_str_mv | AT reubenseyoung isomericlipidsignaturesrevealcompartmentalizedfattyacidmetabolismincancer AT andrewpbowman isomericlipidsignaturesrevealcompartmentalizedfattyacidmetabolismincancer AT kaylyndtousignant isomericlipidsignaturesrevealcompartmentalizedfattyacidmetabolismincancer AT berwyckljpoad isomericlipidsignaturesrevealcompartmentalizedfattyacidmetabolismincancer AT jenniferhgunter isomericlipidsignaturesrevealcompartmentalizedfattyacidmetabolismincancer AT lisakphilp isomericlipidsignaturesrevealcompartmentalizedfattyacidmetabolismincancer AT colleencnelson isomericlipidsignaturesrevealcompartmentalizedfattyacidmetabolismincancer AT shanerellis isomericlipidsignaturesrevealcompartmentalizedfattyacidmetabolismincancer AT ronmaheeren isomericlipidsignaturesrevealcompartmentalizedfattyacidmetabolismincancer AT martincsadowski isomericlipidsignaturesrevealcompartmentalizedfattyacidmetabolismincancer AT stephenjblanksby isomericlipidsignaturesrevealcompartmentalizedfattyacidmetabolismincancer |