TY - JOUR

T1 - Comparison of the effects of long-chain omega-3 fatty acid supplementation on plasma levels of free and esterified oxylipins

AU - Schebb, Nils Helge

AU - Ostermann, Annika I.

AU - Yang, Jun

AU - Hammock, Bruce D

AU - Hahn, Andreas

AU - Schuchardt, Jan Philipp

N1 - Funding information: This study was supported by a Marie Curie Career Integration Grant (CIG 293536) of the European Union and a Grant of the European Union and a Grant of the German Research Foundation (DFG, SCHE 1801) to NHS, and grants from US National Institutes of Health (NIH, R01 ES002710), Environmental Health (NIEHS, P42 ES004699) and Diabetes and Digestive and Kidney Diseases (NIDDK, U24 DK097154) and the West Coast Central Comprehensive Metabolomics Resource Core (WC3MRC) to BDH. BDH is a George and Judy Marcus Senior Fellow of the American Asthma Association. The provision of the fish oil supplement by Dr. Loges and Co. GmbH (Winsen, Germany) is kindly acknowledged. The authors are solely responsible for the design and conduct of the study, collection, management, analysis, and interpretation of the data, as well as preparation of the manuscript. We would like to thank the participants of the study who contributed their time to this project.

PY - 2014/10

Y1 - 2014/10

N2 - 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.SUBJECTS AND METHODS: Subjects (5 male; 5 female) between 46 and 70 years were supplemented with 1.1g/d of eicosapentaenoic acid (EPA) and 0.74g/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.

AB - 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.SUBJECTS AND METHODS: Subjects (5 male; 5 female) between 46 and 70 years were supplemented with 1.1g/d of eicosapentaenoic acid (EPA) and 0.74g/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.

KW - Aged

KW - Dietary Supplements

KW - Esters/blood

KW - Fatty Acids, Omega-3/administration & dosage

KW - Female

KW - Humans

KW - Male

KW - Middle Aged

KW - Oxylipins/blood

KW - Statistics, Nonparametric

KW - PUFA

KW - Eicosanoids

KW - Arachidonic acid

KW - EPA

KW - DHA

KW - Epoxides

KW - Diols

KW - Omega-3 fatty acids

UR - http://www.scopus.com/inward/record.url?scp=84910005590&partnerID=8YFLogxK

U2 - 10.1016/j.prostaglandins.2014.05.002

DO - 10.1016/j.prostaglandins.2014.05.002

M3 - Article

C2 - 24880049

VL - 113-115

SP - 21

EP - 29

JO - Prostaglandins and Other Lipid Mediators

JF - Prostaglandins and Other Lipid Mediators

SN - 1098-8823

ER -