TY - JOUR

T1 - Modulation of blood oxylipin levels by long-chain omega-3 fatty acid supplementation in hyper- and normolipidemic men

AU - Schuchardt, Jan Philipp

AU - Schmidt, Simone

AU - Kressel, Gaby

AU - Willenberg, Ina

AU - Hammock, Bruce D

AU - Hahn, Andreas

AU - Schebb, Nils Helge

N1 - Funding information: This study was supported by a Grant of the German Federal Ministry of Education and Research (BMBF) to AH, 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. We would like to thank the participants of the study who contributed their time to this project.

PY - 2014/1/15

Y1 - 2014/1/15

N2 - Introduction: Long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA) such as EPA and DHA have been shown to possess beneficial health effects, and it is believed that many of their effects are mediated by their oxygenated products (oxylipins). Recently, we have shown that serum levels of several hydroxy, epoxy, and dihydroxy FAs are dependent on the individual status of the parent FAs in a cohort of normo- and hyperlipidemic subjects. So far, the effect of an increased dietary LC n-3 PUFA intake on hydroxy, epoxy, and dihydroxy FA levels has not been investigated in subjects with mild combined hyperlipidemia. Subjects and methods: In the present study, we compared oxylipin patterns of 10 hyperlipidemic (cholesterol >200. mg/dl; triglyceride >150. mg/ml) and 10 normolipidemic men in response to twelve weeks of LC n-3 PUFA intake (1.14. g DHA and 1.56. g EPA). Levels of 44 free hydroxy, epoxy and dihydroxy FAs were analyzed in serum by LC-MS. Additionally, oxylipin levels were compared with their parent PUFA levels in erythrocyte membranes; a biomarker for the individual PUFA status. Results: Differences in the oxylipin pattern between normo- and hyperlipidemic subjects were minor before and after treatment. In all subjects, levels of EPA-derived oxylipins (170-4800. pM) were considerably elevated after LC n-3 PUFA intake (150-1400%), the increase of DHA-derived oxylipins (360-3900. pM) was less pronounced (30-130%). The relative change of EPA in erythrocyte membranes is strongly correlated (r≥0.5; p<0.05) with the relative change of corresponding epoxy and dihydroxy FA serum levels. The effect on arachidonic acid (AA)-derived oxylipin levels (140-27,100. pM) was inconsistent. Discussion and conclusions: The dietary LC PUFA composition has a direct influence on the endogenous oxylipin profile, including several highly biological active EPA- and DHA-derived lipid mediators. The shift in oxylipin pattern appears to be dependent on the initial LC PUFA status particularly for EPA. The finding that also levels of other oxylipins derived from ALA, LA or AA are modified by LC n-3 PUFA intake might suggest that at least some of the effects of EPA and DHA could be mediated by a shift in the entire oxylipin profile.

AB - Introduction: Long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA) such as EPA and DHA have been shown to possess beneficial health effects, and it is believed that many of their effects are mediated by their oxygenated products (oxylipins). Recently, we have shown that serum levels of several hydroxy, epoxy, and dihydroxy FAs are dependent on the individual status of the parent FAs in a cohort of normo- and hyperlipidemic subjects. So far, the effect of an increased dietary LC n-3 PUFA intake on hydroxy, epoxy, and dihydroxy FA levels has not been investigated in subjects with mild combined hyperlipidemia. Subjects and methods: In the present study, we compared oxylipin patterns of 10 hyperlipidemic (cholesterol >200. mg/dl; triglyceride >150. mg/ml) and 10 normolipidemic men in response to twelve weeks of LC n-3 PUFA intake (1.14. g DHA and 1.56. g EPA). Levels of 44 free hydroxy, epoxy and dihydroxy FAs were analyzed in serum by LC-MS. Additionally, oxylipin levels were compared with their parent PUFA levels in erythrocyte membranes; a biomarker for the individual PUFA status. Results: Differences in the oxylipin pattern between normo- and hyperlipidemic subjects were minor before and after treatment. In all subjects, levels of EPA-derived oxylipins (170-4800. pM) were considerably elevated after LC n-3 PUFA intake (150-1400%), the increase of DHA-derived oxylipins (360-3900. pM) was less pronounced (30-130%). The relative change of EPA in erythrocyte membranes is strongly correlated (r≥0.5; p<0.05) with the relative change of corresponding epoxy and dihydroxy FA serum levels. The effect on arachidonic acid (AA)-derived oxylipin levels (140-27,100. pM) was inconsistent. Discussion and conclusions: The dietary LC PUFA composition has a direct influence on the endogenous oxylipin profile, including several highly biological active EPA- and DHA-derived lipid mediators. The shift in oxylipin pattern appears to be dependent on the initial LC PUFA status particularly for EPA. The finding that also levels of other oxylipins derived from ALA, LA or AA are modified by LC n-3 PUFA intake might suggest that at least some of the effects of EPA and DHA could be mediated by a shift in the entire oxylipin profile.

KW - Adult

KW - Dietary Supplements

KW - Eicosapentaenoic Acid/analysis

KW - Erythrocyte Membrane/chemistry

KW - Fatty Acids/analysis

KW - Fatty Acids, Omega-3/pharmacology

KW - Humans

KW - Hyperlipidemias/blood

KW - Lipids/blood

KW - Middle Aged

KW - Oxylipins/blood

KW - Young Adult

KW - Hyperlipidemia

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=84895907696&partnerID=8YFLogxK

U2 - 10.1016/j.plefa.2013.12.008

DO - 10.1016/j.plefa.2013.12.008

M3 - Article

C2 - 24411718

VL - 90

SP - 27

EP - 37

JO - Prostaglandins Leukotrienes and Essential Fatty Acids

JF - Prostaglandins Leukotrienes and Essential Fatty Acids

SN - 0952-3278

IS - 2-3

ER -