TY - JOUR

T1 - Increase of EPA-derived hydroxy, epoxy and dihydroxy fatty acid levels in human plasma after a single dose of long-chain omega-3 PUFA

AU - Schuchardt, Jan Philipp

AU - Schneider, Inga

AU - Willenberg, Ina

AU - Yang, Jun

AU - Hammock, Bruce D

AU - Hahn, Andreas

AU - Schebb, Nils Helge

N1 - Funding information: This study was supported by a Marie Curie Career Integration Grant to NHS, a Kekulé Ph.D. fellowship of the Fonds der Chemischen Industry to IW and a grants from US National Institutes of Health (NIH ), Enviromental Health ( NIEHS , P42 ES004699 and R01 ES002710 ) 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 + 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. All authors had full access to the data and take responsibility for its integrity. All authors have read and agree with the manuscript as written. We would like to thank the participants who contributed their time to this project.

PY - 2014/6

Y1 - 2014/6

N2 - INTRODUCTION: Several supplementation studies with long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA) describe an increase of EPA-derived hydroxy, epoxy and dihydroxy fatty acids in blood, while changes in levels of other LC n-3 and n-6 PUFA-derived oxylipins were minor. In order to investigate the kinetics of changes in oxylipin levels in response to LC n-3 PUFA ingestion, we conducted a single dose treatment study with healthy subjects.SUBJECTS AND METHODS: In the present kinetic study, we compared patterns of hydroxy, epoxy and dihydroxy fatty acids in plasma of 6 healthy men before and after 6, 8, 24, and 48h of fish oil (1008mg EPA and 672mg DHA) ingestion. Levels of EPA- as well as other LC PUFA-derived hydroxy, epoxy and dihydroxy fatty acids were analyzed in plasma by LC-MS. Additionally, levels of these oxylipins were compared with their parent PUFA levels in plasma phospholipids.RESULTS: All EPA-derived oxylipin levels were significantly increased 6h after LC n-3 PUFA ingestion and gradually drop thereafter reaching the baseline levels about 48h after treatment. The relative increase in EPA plasma phospholipid levels highly correlated with the increase of plasma EPA-derived oxylipin levels at different time points. In contrast, plasma levels of arachidonic acid- and DHA-derived oxylipins as well as parent PUFA levels in plasma phospholipids were hardly changed.DISCUSSION AND CONCLUSIONS: Our findings demonstrate that a single dose of LC n-3 PUFAs can rapidly induce a shift in the EPA oxylipin profile of healthy subjects within a few hours. Taking the high biological activity of the EPA-derived epoxy fatty acids into account, even short-term treatment with LC n-3 PUFAs may cause systemic effects, which warrant further investigation.

AB - INTRODUCTION: Several supplementation studies with long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA) describe an increase of EPA-derived hydroxy, epoxy and dihydroxy fatty acids in blood, while changes in levels of other LC n-3 and n-6 PUFA-derived oxylipins were minor. In order to investigate the kinetics of changes in oxylipin levels in response to LC n-3 PUFA ingestion, we conducted a single dose treatment study with healthy subjects.SUBJECTS AND METHODS: In the present kinetic study, we compared patterns of hydroxy, epoxy and dihydroxy fatty acids in plasma of 6 healthy men before and after 6, 8, 24, and 48h of fish oil (1008mg EPA and 672mg DHA) ingestion. Levels of EPA- as well as other LC PUFA-derived hydroxy, epoxy and dihydroxy fatty acids were analyzed in plasma by LC-MS. Additionally, levels of these oxylipins were compared with their parent PUFA levels in plasma phospholipids.RESULTS: All EPA-derived oxylipin levels were significantly increased 6h after LC n-3 PUFA ingestion and gradually drop thereafter reaching the baseline levels about 48h after treatment. The relative increase in EPA plasma phospholipid levels highly correlated with the increase of plasma EPA-derived oxylipin levels at different time points. In contrast, plasma levels of arachidonic acid- and DHA-derived oxylipins as well as parent PUFA levels in plasma phospholipids were hardly changed.DISCUSSION AND CONCLUSIONS: Our findings demonstrate that a single dose of LC n-3 PUFAs can rapidly induce a shift in the EPA oxylipin profile of healthy subjects within a few hours. Taking the high biological activity of the EPA-derived epoxy fatty acids into account, even short-term treatment with LC n-3 PUFAs may cause systemic effects, which warrant further investigation.

KW - Adult

KW - Eicosapentaenoic Acid/blood

KW - Esterification

KW - Fatty Acids, Omega-3/chemistry

KW - Healthy Volunteers

KW - Humans

KW - Kinetics

KW - Male

KW - Oxylipins/blood

KW - Phospholipids/blood

KW - Eicosanoids

KW - Arachidonic acid

KW - Oxylipins

KW - Eicosapentaenoic acid

UR - http://www.scopus.com/inward/record.url?scp=84901621091&partnerID=8YFLogxK

U2 - 10.1016/j.prostaglandins.2014.03.001

DO - 10.1016/j.prostaglandins.2014.03.001

M3 - Article

C2 - 24667634

VL - 109-111

SP - 23

EP - 31

JO - Prostaglandins and Other Lipid Mediators

JF - Prostaglandins and Other Lipid Mediators

SN - 1098-8823

ER -