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Review
, 6 (5), 513-40

Advances in Our Understanding of Oxylipins Derived From Dietary PUFAs

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Review

Advances in Our Understanding of Oxylipins Derived From Dietary PUFAs

Melissa Gabbs et al. Adv Nutr.

Abstract

Oxylipins formed from polyunsaturated fatty acids (PUFAs) are the main mediators of PUFA effects in the body. They are formed via cyclooxygenase, lipoxygenase, and cytochrome P450 pathways, resulting in the formation of prostaglandins, thromboxanes, mono-, di-, and tri-hydroxy fatty acids (FAs), epoxy FAs, lipoxins, eoxins, hepoxilins, resolvins, protectins (also called neuroprotectins in the brain), and maresins. In addition to the well-known eicosanoids derived from arachidonic acid, recent developments in lipidomic methodologies have raised awareness of and interest in the large number of oxylipins formed from other PUFAs, including those from the essential FAs and the longer-chain n-3 (ω-3) PUFAs. Oxylipins have essential roles in normal physiology and function, but can also have detrimental effects. Compared with the oxylipins derived from n-3 PUFAs, oxylipins from n-6 PUFAs generally have greater activity and more inflammatory, vasoconstrictory, and proliferative effects, although there are notable exceptions. Because PUFA composition does not necessarily reflect oxylipin composition, comprehensive analysis of the oxylipin profile is necessary to understand the overall physiologic effects of PUFAs mediated through their oxylipins. These analyses should include oxylipins derived from linoleic and α-linolenic acids, because these largely unexplored bioactive oxylipins constitute more than one-half of oxylipins present in tissues. Because collated information on oxylipins formed from different PUFAs is currently unavailable, this review provides a detailed compilation of the main oxylipins formed from PUFAs and describes their functions. Much remains to be elucidated in this emerging field, including the discovery of more oxylipins, and the understanding of the differing biological potencies, kinetics, and isomer-specific activities of these novel PUFA metabolites.

Keywords: cyclooxygenase; cytochrome P450; eicosanoid; lipid mediators; lipidomics; lipooxygenase; omega-3; omega-6; oxylipin; polyunsaturated fatty acid.

Conflict of interest statement

Author disclosures: M Gabbs, S Leng, JG Devassy, M Monirujjaman, and HM Aukema, no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Arachidonic acid–derived oxylipins. There is also evidence for thromboxane synthase–independent production of HHTrE (416). 11-HETE and 15-HETE are also produced via the COX pathway (24, 25). ASA, acetylsalicylic acid; COX, cyclooxygenase; CYP, cytochrome P450; DiHETE, dihydroxy-eicosatetraenoic acid; DiHETrE, dihydroxy-eicosatrienoic acid; EpETrE, epoxy-eicosatrienoic acid; Ex, eoxin; HETE, hydroxy-eicosatetraenoic acid; HHTrE, hydroxy-heptadecatrienoic acid; HpETE, hydroperoxy-eicosatetraenoic acid; Hx, hepoxilin; LOX, lipoxygenase; Lt, Leukotriene; Lx, lipoxin; oxo-ETE, oxo-eicosatetraenoic acid; PGEM, prostaglandin E metabolite; Trx, trioxilin; Tx, thromboxane.
FIGURE 2
FIGURE 2
Linoleic acid–derived oxylipins. 9-HODE and 13-HODE are also produced via the COX pathway (27, 61). COX, cyclooxygenase; CYP, cytochrome P450; DiHOME, dihydroxy-octadecenoic acid; EpOME, epoxy-octadecenoic acid; HODE, hydroxy-octadecadienoic acid; HpODE, hydroperoxy-octadecadienoic acid; LOX, lipoxygenase; oxo-ODE, oxo-octadecadienoic acid; TriHOME, trihydroxy-octadecenoic acid.
FIGURE 3
FIGURE 3
Dihomo-γ-linolenic acid–derived oxylipins. COX, cyclooxygenase; CYP, cytochrome P450; DiHEDE, dihydroxy-eicosadienoic acid; EpEDE, epoxy-eicosadienoic acid; HETrE, hydroxy-eicosatrienoic acid; HpETrE, hydroperoxy-eicosatrienoic acid; LOX, lipoxygenase; Tx, thromboxane.
FIGURE 4
FIGURE 4
Adrenic acid–derived oxylipins. Dihomo-7,14-DiHETE and dihomo-7,17-DiHETE also can be formed from dihomo-7-HETE (76). COX, cyclooxygenase; CYP, cytochrome P450; DiHETE, dihydroxy-eicosatetraenoic acid; DiHETrE, dihydroxy-eicosatrienoic acid; EpETrE, epoxy-eicosatrienoic acid; HETE, hydroxy-eicosatetraenoic acid; HpETE, hydroperoxy-eicosatetraenoic acid; LOX, lipoxygenase; Tx, thromboxane.
FIGURE 5
FIGURE 5
α-Linolenic acid–derived oxylipins. CYP, cytochrome P450; DiHODE, dihydroxy-octadecadienoic acid; DiHOTrE, dihydroxy-octadecatrienoic acid; EpODE, epoxy-octadecadienoic acid; HOTrE, hydroxy-octadecatrienoic acid; HpOTrE, hydroperoxy-octadecatrienoic acid; LOX, lipoxygenase; oxo-OTrE, oxo-​octadecatrienoic acid.
FIGURE 6
FIGURE 6
EPA-derived oxylipins. ASA, acetylsalicylic acid; COX, cyclooxygenase; CYP, cytochrome P450; DiHEPE, dihydroxy-eicosapentaenoic acid; DiHETE, dihydroxy-eicosatetraenoic acid; EpETE, epoxy-eicosatetraenoic acid; HEPE, hydroxy-eicosapentaenoic acid; HpEPE, hydroperoxy-eicosapentaenoic acid; LOX, lipoxygenase; Lt, Leukotriene; Lx, lipoxin; oxo-EPE, oxo-eicosapentaenoic acid; Rv, resolvin; Tx, thromboxane.
FIGURE 7
FIGURE 7
DHA-derived oxylipins. 13-HDoHE also is produced via the COX pathway (26). 14,21-DiHDoHE also may be formed from 21-HDoHE (313, 314). ASA, acetylsalicylic acid; AT, aspirin-triggered; COX, cyclooxygenase; CYP, cytochrome P450; DiHDoHE, dihydroxy-docosahexaenoic acid; DiHDPE, dihydroxy-docosapentaenoic acid; EpDPE, epoxy-docosapentaenoic acid; HDoHE, hydroxy-docosahexaenoic acid; HpDoHE, hydroperoxy-docosahexaenoic acid; LOX, lipoxygenase; MaR, maresin; oxo-DoHE, oxo-docosahexaenoic acid; PD, protectin; Rv, resolvin.

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