Artifactual FA dimers mimic FAHFA signals in untargeted metabolomics pipelines.
LC-MS/MS
adipose tissue
insulin resistance
isobaric FA dimers
lipidomics
lipids
lipokines
obesity
olefinic bond
spectral database
Journal
Journal of lipid research
ISSN: 1539-7262
Titre abrégé: J Lipid Res
Pays: United States
ID NLM: 0376606
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
received:
02
03
2022
revised:
15
03
2022
accepted:
16
03
2022
pubmed:
23
3
2022
medline:
25
5
2022
entrez:
22
3
2022
Statut:
ppublish
Résumé
FA esters of hydroxy FAs (FAHFAs) are lipokines with extensive structural and regional isomeric diversity that impact multiple physiological functions, including insulin sensitivity and glucose homeostasis. Because of their low molar abundance, FAHFAs are typically quantified using highly sensitive LC-MS/MS methods. Numerous relevant MS databases house in silico-spectra that allow identification and speciation of FAHFAs. These provisional chemical feature assignments provide a useful starting point but could lead to misidentification. To address this possibility, we analyzed human serum with a commonly applied high-resolution LC-MS untargeted metabolomics platform. We found that many chemical features are putatively assigned to the FAHFA lipid class based on exact mass and fragmentation patterns matching spectral databases. Careful validation using authentic standards revealed that many investigated signals provisionally assigned as FAHFAs are in fact FA dimers formed in the LC-MS pipeline. These isobaric FA dimers differ structurally only by the presence of an olefinic bond. Furthermore, stable isotope-labeled oleic acid spiked into human serum at subphysiological concentrations showed concentration-dependent formation of a diverse repertoire of FA dimers that analytically mimicked FAHFAs. Conversely, validated FAHFA species did not form spontaneously in the LC-MS pipeline. Together, these findings underscore that FAHFAs are endogenous lipid species. However, nonbiological FA dimers forming in the setting of high concentrations of FFAs can be misidentified as FAHFAs. Based on these results, we assembled a FA dimer database to identify nonbiological FA dimers in untargeted metabolomics datasets.
Identifiants
pubmed: 35315332
pii: S0022-2275(22)00034-7
doi: 10.1016/j.jlr.2022.100201
pmc: PMC9034316
pii:
doi:
Substances chimiques
Esters
0
Fatty Acids
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
100201Subventions
Organisme : NIA NIH HHS
ID : R01 AG069781
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK091538
Pays : United States
Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest P. A. C. has served as an external consultant for Pfizer, Inc, Abbott Laboratories, and Janssen Research & Development. All other authors declare that they have no conflicts of interest with the contents of this article.
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