Artifactual FA dimers mimic FAHFA signals in untargeted metabolomics pipelines

Nelson, Alisa B.; Chow, Lisa S.; Hughey, Curtis C.; Crawford, Peter A.; Puchalska, Patrycja

doi:10.1016/j.jlr.2022.100201

Cited by 13 publications

(7 citation statements)

References 49 publications

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“…17 ). Diagnostic fragment ions for discrimination of FAHFA from possible fatty acyl dimers were used to curate these species from plasma 60 , in addition to RT and CCS reference of the standard (Supplementary Fig. 18 ).…”

Section: Methodsmentioning

confidence: 99%

Four-dimensional trapped ion mobility spectrometry lipidomics for high throughput clinical profiling of human blood samples

et al. 2023

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Lipidomics encompassing automated lipid extraction, a four-dimensional (4D) feature selection strategy for confident lipid annotation as well as reproducible and cross-validated quantification can expedite clinical profiling. Here, we determine 4D descriptors (mass to charge, retention time, collision cross section, and fragmentation spectra) of 200 lipid standards and 493 lipids from reference plasma via trapped ion mobility mass spectrometry to enable the implementation of stringent criteria for lipid annotation. We use 4D lipidomics to confidently annotate 370 lipids in reference plasma samples and 364 lipids in serum samples, and reproducibly quantify 359 lipids using level-3 internal standards. We show the utility of our 4D lipidomics workflow for high-throughput applications by reliable profiling of intra-individual lipidome phenotypes in plasma, serum, whole blood, venous and finger-prick dried blood spots.

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Section: Methodsmentioning

confidence: 99%

Four-dimensional trapped ion mobility spectrometry lipidomics for high throughput clinical profiling of human blood samples

et al. 2023

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“…The study is strengthened using a quantitative, targeted lipidomics platform to measure FAHFAs in human serum. Previous work from our lab has shown that untargeted metabolomics analytical methods are susceptible to the formation of fatty acid dimers that mimic FAHFAs, thus confounding interpretation [ 19 ]. Here we use both solid phase extraction and careful identification of FAHFAs by selected ion monitoring to ensure proper identification and quantification of this lipid class and their species.…”

Section: Resultsmentioning

confidence: 99%

Gender-based heterogeneity of FAHFAs in trained runners

Nelson,

Chow,

Dengel

et al. 2024

PLoS ONE

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Fatty acid esters of hydroxy fatty acid (FAHFA) are anti-diabetic and anti-inflammatory lipokines. Recently FAHFAs were also found to predict cardiorespiratory fitness in a cross-sectional study of recreationally trained runners. Here we report the influences of body composition and gender on static FAHFA abundances in circulation. We compared the association between circulating FAHFA concentrations and body composition, determined by dual x-ray absorptiometry, in female recreational runners who were lean (BMI < 25 kg/m2, n = 6), to those who were overweight (BMI ≥ 25 kg/m2, n = 7). To characterize the effect of gender we also compared circulating FAHFAs in lean male recreational runners (n = 8) to recreationally trained lean female (n = 6) runner group. Circulating FAHFAs were increased in females in a manner that was modulated by specific adipose depot sizes, blood glucose, and lean body mass. As expected, circulating FAHFAs were diminished in the overweight group, but strikingly, within the lean cohort, increases in circulating FAHFAs were promoted by increased fat mass, relative to lean mass, while the overweight group showed a significantly attenuated relationship. These studies suggest multimodal regulation of circulating FAHFAs and raise hypotheses to test endogenous FAHFA dynamic sources and sinks in health and disease, which will be essential for therapeutic target development. Baseline circulating FAHFA concentrations could signal sub-clinical metabolic dysfunction in metabolically healthy obesity.

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“…FAHFAs were prone to fragmentation at the junction of two fatty acid chains, 13 and their precursor ions and three product ions were all observed in the MS/MS spectrum, including a characteristic ion (297.24286 in FAHFA 18:1/18:1, 173.11696 in FAHFA 18:1/ 9:0, 159.10133 in FAHFA 18:1/8:0, 187.13275 in FAHFA 18:1/10:0) for distinguishing FAHFAs from dimers. 59 However, the position of the connection between two fatty acids of FAHFA had difficulties being confirmed by the MS/MS spectrum. Four FAHFAs consisted of FA 8:0, FA 9:0, FA 10:0, and FA 18:1, and the first three fatty acids were formed through fragmentation of FA 18:1.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Unraveling the Thermal Oxidation Products and Peroxidation Mechanisms of Different Chemical Structures of Lipids: An Example of Molecules Containing Oleic Acid

Zhou

Zhao

et al. 2022

J. Agric. Food Chem.

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Lipid structures affect lipid oxidation, causing differences in types and contents of volatiles and nonvolatiles in various foods. In this study, the oxidation differences of monoacylglycerol (MAG), triacylglycerol (TAG), phosphatidylethanolamine (PE), and phosphatidylcholine (PC) with oleoyl residues and oleic acid (FA) during thermal treatment were investigated. Volatiles and nonvolatiles were monitored by gas chromatography−mass spectrometry and ultrahigh-performance liquid chromatography-Q-Exactive HF-X Orbitrap Mass Spectrometer, respectively. The results showed that the structures of MAG and TAG could delay the chain initiation reaction. The polar heads of PC and PE remarkably influenced the oxidation rate and the formation of the oxidation products probably due to the hydrogen bonds formed with free radicals. Among the volatile oxidation products, aldehydes, acids, and furans with eight or nine carbon atoms accounted for the majority in FA, MAG, TAG, and PC samples, but PE samples mainly generated ketones with nine or 10 carbon atoms. The formation of nonvolatile products in TAG samples possessed significant stagespecific changes. Fatty acid esters of hydroxy fatty acids were only produced in the free fatty acid oxidation model. The activity of chemical bonds participating in the truncation reaction decreased to both sides from the double bond position.

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Artifactual FA dimers mimic FAHFA signals in untargeted metabolomics pipelines

Cited by 13 publications

References 49 publications

Four-dimensional trapped ion mobility spectrometry lipidomics for high throughput clinical profiling of human blood samples

Four-dimensional trapped ion mobility spectrometry lipidomics for high throughput clinical profiling of human blood samples

Gender-based heterogeneity of FAHFAs in trained runners

Unraveling the Thermal Oxidation Products and Peroxidation Mechanisms of Different Chemical Structures of Lipids: An Example of Molecules Containing Oleic Acid

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