Comparison of the effects of long-chain omega-3 fatty acid supplementation on plasma levels of free and esterified oxylipins

Nils Helge Schebb, Annika I. Ostermann, Jun Yang, Bruce D. Hammock, Andreas Hahn, Jan Philipp Schuchardt

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Subjects and methods Subjects (5 male; 5 female) between 46 and 70 years were supplemented with 1.1 g/d of eicosapentaenoic acid (EPA) and 0.74 g/d docosahexaenoic acid (DHA) as ethyl esters. Blood samples were drawn before and after twelve weeks of treatment. Oxylipins in plasma were analyzed by LC-MS directly for free oxylipins and after saponification. Relative FA composition in erythrocyte membranes was analyzed by GC.

Results LC n-3 PUFA treatment led to a significant increase in EPA (200%) and DHA (23%) in erythrocyte membranes. Of the oxylipins measured in plasma, total and free EPA-derived metabolites were highly increased (70-150%), while total AA-derived metabolites were decreased on average by 30%. There was no effect on DHA-metabolites. Concentrations of total hydroxy and epoxy FAs in plasma were considerably higher compared to free hydroxy and epoxy FAs (up to 350 times), while levels of most free dihydroxy FAs were in a similar range to total dihydroxy FAs. However, the individual ratios between total and free plasma oxylipins remained unchanged after LC n-3 PUFA treatment.

Discussion and conclusions LC n-3 PUFA supplementation causes a shift in the levels of circulating oxylipins, having the strongest impact on EPA-derived epoxy, dihydroxy and hydroxy FA. The unchanged ratio of free and esterified oxylipins in plasma indicates that both concentrations are valuable biomarkers for assessing the individual status of these lipid mediators.

Introduction It is believed that many of the beneficial effects of long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA) are mediated by their oxidized metabolites, the oxylipins. The formation and biological role of many cytochrome P450 and lipoxygenase derived hydroxy, epoxy and dihydroxy FA, particularly of oxylipins esterified in polar lipids and triglycerides remain unclear. In this study, we compared the impact of twelve weeks of LC n-3 PUFA supplementation on the patterns of free and total (sum of esterified and free) hydroxy, epoxy and dihydroxy FAs.

Original languageEnglish (US)
Pages (from-to)21-29
Number of pages9
JournalProstaglandins and Other Lipid Mediators
Volume113-115
DOIs
StatePublished - May 29 2014
Externally publishedYes

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Oxylipins
Omega-3 Fatty Acids
Plasmas
Eicosapentaenoic Acid
Metabolites
Docosahexaenoic Acids
Erythrocyte Membrane
Saponification
Membranes
Lipids
Lipoxygenase
Biomarkers
Unsaturated Fatty Acids
Cytochrome P-450 Enzyme System
Esters
Triglycerides
Blood

Keywords

  • Arachidonic acid
  • DHA
  • Diols
  • Eicosanoids
  • EPA
  • Epoxides
  • Omega-3 fatty acids
  • PUFA

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Pharmacology
  • Cell Biology

Cite this

Comparison of the effects of long-chain omega-3 fatty acid supplementation on plasma levels of free and esterified oxylipins. / Schebb, Nils Helge; Ostermann, Annika I.; Yang, Jun; Hammock, Bruce D.; Hahn, Andreas; Schuchardt, Jan Philipp.

In: Prostaglandins and Other Lipid Mediators, Vol. 113-115, 29.05.2014, p. 21-29.

Research output: Contribution to journalArticle

Schebb, Nils Helge ; Ostermann, Annika I. ; Yang, Jun ; Hammock, Bruce D. ; Hahn, Andreas ; Schuchardt, Jan Philipp. / Comparison of the effects of long-chain omega-3 fatty acid supplementation on plasma levels of free and esterified oxylipins. In: Prostaglandins and Other Lipid Mediators. 2014 ; Vol. 113-115. pp. 21-29.
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abstract = "Subjects and methods Subjects (5 male; 5 female) between 46 and 70 years were supplemented with 1.1 g/d of eicosapentaenoic acid (EPA) and 0.74 g/d docosahexaenoic acid (DHA) as ethyl esters. Blood samples were drawn before and after twelve weeks of treatment. Oxylipins in plasma were analyzed by LC-MS directly for free oxylipins and after saponification. Relative FA composition in erythrocyte membranes was analyzed by GC.Results LC n-3 PUFA treatment led to a significant increase in EPA (200{\%}) and DHA (23{\%}) in erythrocyte membranes. Of the oxylipins measured in plasma, total and free EPA-derived metabolites were highly increased (70-150{\%}), while total AA-derived metabolites were decreased on average by 30{\%}. There was no effect on DHA-metabolites. Concentrations of total hydroxy and epoxy FAs in plasma were considerably higher compared to free hydroxy and epoxy FAs (up to 350 times), while levels of most free dihydroxy FAs were in a similar range to total dihydroxy FAs. However, the individual ratios between total and free plasma oxylipins remained unchanged after LC n-3 PUFA treatment.Discussion and conclusions LC n-3 PUFA supplementation causes a shift in the levels of circulating oxylipins, having the strongest impact on EPA-derived epoxy, dihydroxy and hydroxy FA. The unchanged ratio of free and esterified oxylipins in plasma indicates that both concentrations are valuable biomarkers for assessing the individual status of these lipid mediators.Introduction It is believed that many of the beneficial effects of long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA) are mediated by their oxidized metabolites, the oxylipins. The formation and biological role of many cytochrome P450 and lipoxygenase derived hydroxy, epoxy and dihydroxy FA, particularly of oxylipins esterified in polar lipids and triglycerides remain unclear. In this study, we compared the impact of twelve weeks of LC n-3 PUFA supplementation on the patterns of free and total (sum of esterified and free) hydroxy, epoxy and dihydroxy FAs.",
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AU - Yang, Jun

AU - Hammock, Bruce D.

AU - Hahn, Andreas

AU - Schuchardt, Jan Philipp

PY - 2014/5/29

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N2 - Subjects and methods Subjects (5 male; 5 female) between 46 and 70 years were supplemented with 1.1 g/d of eicosapentaenoic acid (EPA) and 0.74 g/d docosahexaenoic acid (DHA) as ethyl esters. Blood samples were drawn before and after twelve weeks of treatment. Oxylipins in plasma were analyzed by LC-MS directly for free oxylipins and after saponification. Relative FA composition in erythrocyte membranes was analyzed by GC.Results LC n-3 PUFA treatment led to a significant increase in EPA (200%) and DHA (23%) in erythrocyte membranes. Of the oxylipins measured in plasma, total and free EPA-derived metabolites were highly increased (70-150%), while total AA-derived metabolites were decreased on average by 30%. There was no effect on DHA-metabolites. Concentrations of total hydroxy and epoxy FAs in plasma were considerably higher compared to free hydroxy and epoxy FAs (up to 350 times), while levels of most free dihydroxy FAs were in a similar range to total dihydroxy FAs. However, the individual ratios between total and free plasma oxylipins remained unchanged after LC n-3 PUFA treatment.Discussion and conclusions LC n-3 PUFA supplementation causes a shift in the levels of circulating oxylipins, having the strongest impact on EPA-derived epoxy, dihydroxy and hydroxy FA. The unchanged ratio of free and esterified oxylipins in plasma indicates that both concentrations are valuable biomarkers for assessing the individual status of these lipid mediators.Introduction It is believed that many of the beneficial effects of long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA) are mediated by their oxidized metabolites, the oxylipins. The formation and biological role of many cytochrome P450 and lipoxygenase derived hydroxy, epoxy and dihydroxy FA, particularly of oxylipins esterified in polar lipids and triglycerides remain unclear. In this study, we compared the impact of twelve weeks of LC n-3 PUFA supplementation on the patterns of free and total (sum of esterified and free) hydroxy, epoxy and dihydroxy FAs.

AB - Subjects and methods Subjects (5 male; 5 female) between 46 and 70 years were supplemented with 1.1 g/d of eicosapentaenoic acid (EPA) and 0.74 g/d docosahexaenoic acid (DHA) as ethyl esters. Blood samples were drawn before and after twelve weeks of treatment. Oxylipins in plasma were analyzed by LC-MS directly for free oxylipins and after saponification. Relative FA composition in erythrocyte membranes was analyzed by GC.Results LC n-3 PUFA treatment led to a significant increase in EPA (200%) and DHA (23%) in erythrocyte membranes. Of the oxylipins measured in plasma, total and free EPA-derived metabolites were highly increased (70-150%), while total AA-derived metabolites were decreased on average by 30%. There was no effect on DHA-metabolites. Concentrations of total hydroxy and epoxy FAs in plasma were considerably higher compared to free hydroxy and epoxy FAs (up to 350 times), while levels of most free dihydroxy FAs were in a similar range to total dihydroxy FAs. However, the individual ratios between total and free plasma oxylipins remained unchanged after LC n-3 PUFA treatment.Discussion and conclusions LC n-3 PUFA supplementation causes a shift in the levels of circulating oxylipins, having the strongest impact on EPA-derived epoxy, dihydroxy and hydroxy FA. The unchanged ratio of free and esterified oxylipins in plasma indicates that both concentrations are valuable biomarkers for assessing the individual status of these lipid mediators.Introduction It is believed that many of the beneficial effects of long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA) are mediated by their oxidized metabolites, the oxylipins. The formation and biological role of many cytochrome P450 and lipoxygenase derived hydroxy, epoxy and dihydroxy FA, particularly of oxylipins esterified in polar lipids and triglycerides remain unclear. In this study, we compared the impact of twelve weeks of LC n-3 PUFA supplementation on the patterns of free and total (sum of esterified and free) hydroxy, epoxy and dihydroxy FAs.

KW - Arachidonic acid

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KW - EPA

KW - Epoxides

KW - Omega-3 fatty acids

KW - PUFA

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