Isomeric lipid signatures reveal compartmentalized fatty acid metabolism in cancer

Young, Reuben S. E.; Bowman, Andrew P.; Tousignant, Kaylyn D.; Poad, Berwyck L. J.; Gunter, Jennifer H.; Philp, Lisa; Nelson, Colleen C.; Ellis, Shane R.; Heeren, Ron M. A.; Sadowski, Martin C.; Blanksby, Stephen J.

doi:10.1016/j.jlr.2022.100223

Cited by 13 publications

(14 citation statements)

References 70 publications

(97 reference statements)

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Section: Cancermentioning

confidence: 99%

“…A recent study using stable isotope labeled fatty acids and mass spectrometry measurements in the prostate cancer cell line LNCaP has highlighted the existence of compartmentalized regulation of fatty acid utilization [ 20 ]. This may result in disparate metabolic fates and cellular functions for isomeric fatty acids such as those of the hexadecenoic fatty acid family, i.e., 16:1n-7, 16:1n-9, and 16:1n-10 [ 20 ]. The differential incorporation of fatty acids into individual phospholipid species raises the intriguing possibility that lipid isomers could be regarded as potential biomarkers for disease progression in tumor tissues, with the hexadecenoic fatty acid family likely playing a prominent role.…”

Section: Cancermentioning

confidence: 99%

“…Palmitic acid and the polyunsaturated fatty acids of the n-3 and n-6 series are competitors for the Δ6 desaturase reaction, which may limit the amount of 16:1n-10 produced by some cells [ 10 , 18 ]. It is striking that, while SCD-1-mediated Δ9 desaturation (leading to 16:1n-7 formation) takes place in the endoplasmic reticulum, FADS2-mediated Δ6 desaturation (leading to 16:1n-10 formation) also occurs in the mitochondria [ 19 , 20 ]. The later organelle is also the site of synthesis of 16:1n-9 via β-oxidation [ 9 ] ( Figure 1 ).…”

Section: Introductionmentioning

confidence: 99%

“…The later organelle is also the site of synthesis of 16:1n-9 via β-oxidation [ 9 ] ( Figure 1 ). Clearly, compartmentalization of lipid synthesis, turnover and signaling must play a paramount role in regulating the metabolic and inflammatory reactions of cells and tissues [ 19 , 20 , 21 ]. In particular, the partition of palmitic acid between Δ9 (synthesis of palmitoleic acid) and Δ6 desaturase pathways (synthesis of sapienic acid) is beginning to be considered as a metabolic switch in health and disease [ 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

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Roles of Palmitoleic Acid and Its Positional Isomers, Hypogeic and Sapienic Acids, in Inflammation, Metabolic Diseases and Cancer

Bermúdez

Pereira

Fraile

et al. 2022

Cells

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In the last few years, the monounsaturated hexadecenoic fatty acids are being increasingly considered as biomarkers of health with key functions in physiology and pathophysiology. Palmitoleic acid (16:1n-7) and sapienic acid (16:1n-10) are synthesized from palmitic acid by the action of stearoyl-CoA desaturase-1 and fatty acid desaturase 2, respectively. A third positional isomer, hypogeic acid (16:1n-9) is produced from the partial β-oxidation of oleic acid. In this review, we discuss the current knowledge of the effects of palmitoleic acid and, where available, sapienic acid and hypogeic acid, on metabolic diseases such as diabetes, cardiovascular disease, and nonalcoholic fatty liver disease, and cancer. The results have shown diverse effects among studies in cell lines, animal models and humans. Palmitoleic acid was described as a lipokine able to regulate different metabolic processes such as an increase in insulin sensitivity in muscle, β cell proliferation, prevention of endoplasmic reticulum stress and lipogenic activity in white adipocytes. Numerous beneficial effects have been attributed to palmitoleic acid, both in mouse models and in cell lines. However, its role in humans is not fully understood, and is sometimes controversial. Regarding sapienic acid and hypogeic acid, studies on their biological effects are still scarce, but accumulating evidence suggests that they also play important roles in metabolic regulation. The multiplicity of effects reported for palmitoleic acid and the compartmentalized manner in which they often occur, may suggest the overlapping actions of multiple isomers being present at the same or neighboring locations.

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Section: Cancermentioning

confidence: 99%

Section: Cancermentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Roles of Palmitoleic Acid and Its Positional Isomers, Hypogeic and Sapienic Acids, in Inflammation, Metabolic Diseases and Cancer

Bermúdez

Pereira

Fraile

et al. 2022

Cells

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“…1,4,5 Importantly, recent research implicates alterations in FA structure and/or composition associated with lipid metabolism dysregulation in numerous pathologies, including cancer, cardiovascular diseases, neurodegeneration, and diabetes. [6][7][8][9][10][11][12][13] For example, long-chain saturated fatty acids were identified as the toxic factor killing injured neurons and oligodendrocytes in the brain during inflammation. 14 Consequently, analytical methods capable of accurately identifying and quantifying FAs in complex biological samples are needed in order to unravel their roles in health and disease.…”

Section: Introductionmentioning

confidence: 99%

Identification of monomethyl branched chain lipids by a combination of liquid chromatography tandem mass spectrometry and charge-switching chemistries

Randolph

Beveridge

Iyer

et al. 2022

Preprint

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While various mass spectrometric approaches have been applied to lipid analysis, unraveling the extensive structural diversity of lipids remains a significant challenge. Notably, these approaches often fail to differentiate between isomeric lipids - a challenge that is particularly acute for branched-chain fatty acids (FAs) that often share similar (or identical) mass spectra to their straight-chain isomers. Here, we utilize charge-switching strategies that combine ligated magnesium dications with deprotonated fatty acid anions. Subsequent activation of these charge inverted anions yields mass spectra that differentiate anteiso branched- from straight-chain and iso branched-chain FA isomers with the predictable fragmentation enabling de novo assignment of anteiso branch points. Application of these charge-inversion chemistries in both gas- and solution-phase modalities is demonstrated to assign the position of anteiso-methyl branch-points in FAs, and can be extended to de novo assignment of additional branching sites via predictable fragmentation patterns as methyl branching site(s) move closer to the carboxyl carbon. The gas phase approach is shown to be compatible with top-down structure elucidation of complex lipids such as phosphatidylcholines, while integration of solution-phase charge-inversion with reversed phase liquid chromatography enables separation and unambiguous identification of FA structures within isomeric mixtures. Taken together, the presented charge switching MS-based technique, in combination with liquid chromatography enables the structural identification of branched-chain FA without the requirement of authentic methyl branched FA reference standards.

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Deep Characterisation of the sn‐Isomer Lipidome Using High‐Throughput Data‐Independent Acquisition and Ozone‐Induced Dissociation**

Michael,

Young,

Balez

et al. 2024

Angewandte Chemie

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In recent years there has been a significant interest in the development of innovative lipidomics techniques capable of resolving lipid isomers. To date, methods applied to resolving sn‐isomers have resolved only a limited number of species. We report a workflow based on ozone‐induced dissociation for untargeted characterisation of hundreds of sn‐resolved glycerophospholipid isomers from biological extracts in under 20 minutes, coupled with an automated data analysis pipeline. It provides an order of magnitude increase over the number of sn‐isomer pairs identified compared to previous reports and reveals that sn‐isomer populations are tightly regulated and significantly different between cell lines. The sensitivity of this method and potential for de novo molecular discovery is further demonstrated by the identification of unexpected lipids containing ultra‐long chain monounsaturated acyl chains at the sn‐1 position.

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Isomeric lipid signatures reveal compartmentalized fatty acid metabolism in cancer

Cited by 13 publications

References 70 publications

Roles of Palmitoleic Acid and Its Positional Isomers, Hypogeic and Sapienic Acids, in Inflammation, Metabolic Diseases and Cancer

Roles of Palmitoleic Acid and Its Positional Isomers, Hypogeic and Sapienic Acids, in Inflammation, Metabolic Diseases and Cancer

Identification of monomethyl branched chain lipids by a combination of liquid chromatography tandem mass spectrometry and charge-switching chemistries

Deep Characterisation of the sn‐Isomer Lipidome Using High‐Throughput Data‐Independent Acquisition and Ozone‐Induced Dissociation**

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