Abstract

Our objective was to assess the dynamics of monoepoxides derived from polyunsaturated fatty acids (MEFAs), and their response to n-3 PUFA supplementation, in the setting of acute tissue injury and inflammation (cardiac surgery) in humans. Patients (479) undergoing cardiac surgery in three countries were randomized to perioperative fish oil (EPA + DHA; 8-10 g over 2-5 days preoperatively, then 2 g/day postoperatively) or placebo (olive oil). Plasma MEFAs derived from n-3 and n-6 PUFAs were measured 2 days postoperatively. Based on serial measures in a subset of the placebo group, levels of all MEFAs declined substantially following surgery (at postoperative day 2), with declines ranging from 37% to 63% (P < 0.05 each). Compared with placebo at postoperative day 2, levels of EPA- and DHA-derived MEFAs were 40% and 18% higher, respectively (P ≤ 0.004). The n-3 PUFA supplementation did not significantly alter the decline in n-6 PUFA-derived MEFAs. Both enrollment level and changes in plasma phospholipid EPA and DHA were associated with their respective MEFAs at postoperative day 2 (P < 0.001). Under the acute stress of cardiac surgery, n-3 PUFA supplementation significantly ameliorated the reduction in postoperative n-3 MEFAs, but not n-6 MEFAs, and the degree of increase in n-3 MEFAs related positively to the circulating level of their n-3 PUFA precursors.

Highlights

  • Our objective was to assess the dynamics of monoepoxides derived from polyunsaturated fatty acids (MEFAs), and their response to n-3 omega-6 PUFA (PUFA) supplementation, in the setting of acute tissue injury and inflammation in humans

  • MEFAs have rarely been measured in humans, and important questions remain regarding their usual physiological concentrations, the interrelationship between different MEFAs derived from different classes of PUFAs, and if and by how much endogenous levels of Abbreviations: AA, arachidonic acid; CV, coefficient of variation; CYP450, cytochrome P450; EET, epoxyeicosatrienoic acid; LA, linoleic acid; MEFA, monoepoxide derived from polyunsaturated fatty acid; n-3 PUFA, omega-3 PUFA; n-6 PUFA, omega-6 PUFA; OPERA, Omega-3 Fatty Acids for Prevention of Postoperative Atrial Fibrillation; PoAF, postoperative atrial fibrillation

  • When we evaluated the association of plasma phospholipid PUFAs at enrollment with their respective MEFAs at postoperative day 2, levels of plasma phospholipids EPA, DHA, and AA, but not LA, were each positively associated with their respective MEFAs (Table 3)

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Summary

Introduction

Our objective was to assess the dynamics of monoepoxides derived from polyunsaturated fatty acids (MEFAs), and their response to n-3 PUFA supplementation, in the setting of acute tissue injury and inflammation (cardiac surgery) in humans. The n-3 PUFA supplementation did not significantly alter the decline in n-6 PUFA-derived MEFAs. The n-3 PUFA supplementation did not significantly alter the decline in n-6 PUFA-derived MEFAs Both enrollment level and changes in plasma phospholipid EPA and DHA were associated with their respective MEFAs at postoperative day 2 (P < 0.001). One key class of these metabolic regulators is the monoepoxides derived from polyunsaturated fatty acids (MEFAs), synthesized from long-chain omega-3 (n-3) and omega-6 (n-6) PUFAs by cytochrome P450 (CYP450) enzymes (Fig. 1) [6]. MEFAs could be altered by changing dietary intake of their PUFA precursors These questions are relevant in the setting of acute tissue injury and stress, when their inflammation-resolving activities may be most relevant

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