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Review
. 2024 Nov 7;16(22):3812.
doi: 10.3390/nu16223812.

Oxylipins Derived from PUFAs in Cardiometabolic Diseases: Mechanism of Actions and Possible Nutritional Interactions

Duygu Ağagündüz  1 , Özge Yeşildemir  2 , Emine Koçyiğit  3 , Tevfik Koçak  4 , Buket Özen Ünaldı  5 , Gamze Ayakdaş  6 , Ferenc Budán  7
Affiliations
Review

Oxylipins Derived from PUFAs in Cardiometabolic Diseases: Mechanism of Actions and Possible Nutritional Interactions

Duygu Ağagündüz et al. Nutrients. .

Abstract

Oxylipins are oxidized fatty acids, both saturated and unsaturated, formed through pathways that involve singlet oxygen or dioxygen-mediated oxygenation reactions and are primarily produced by enzyme families such as cyclooxygenases, lipoxygenases, and cytochrome P450. These lipid-based complex bioactive molecules are pivotal signal mediators, acting in a hormone-like manner in the pathophysiology of numerous diseases, especially cardiometabolic diseases via modulating plenty of mechanisms. It has been reported that omega-6 and omega-3 oxylipins are important novel biomarkers of cardiometabolic diseases. Moreover, collected literature has noted that diet and dietary components, especially fatty acids, can modulate these oxygenated lipid products since they are mainly derived from dietary omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) or linoleic acid and α-linolenic by elongation and desaturation pathways. This comprehensive review aims to examine their correlations to cardiometabolic diseases and how diets modulate oxylipins. Also, some aspects of developing new biomarkers and therapeutical utilization are detailed in this review.

Keywords: PUFA; cardiometabolic diseases; lipidomics; oxylipins.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Summary of oxylipins synthesized from PUFAs. PUFA: Polyunsaturated fatty acids, LA: Linoleic acid, GLA: γ-linolenic acid, DGLA: Dihomo-γ-linolenic acid, AdA: Adrenic acid, AA: Arachidonic acid, ALA: α-Linolenic acid, EPA: Eicosapentaenoic acid, DHA: Docosapentaenoic acid, COX: Cyclooxygenase, LOX: Lipoxygenase, CYP: Cytochrome P450, HpODE: hydroperoxy-octadecadienoic acid, HODE: Hydroxy-octadecadienoic acid, EpOME: Epoxy-octadecenoic acid, diHOME: Dihydroxy-octadecenoic acid, HOTrE: Hydroxy-octadecatrienoic acid, HpETrE: Hydroperoxy-eicosatrienoic acid, EpEDE: Epoxy-eicosadienoic acid, DiHEDE: Dihydroxy-eicosadienoic acid, HETE: Hydroxy-eicosatetraenoic acid, DiHETE: Dihydroxy-eicosatetraenoic acid, DiHETrE: Dihydroxy-eicosatrienoic acid, HpETE: Hydroperoxy-eicosatetraenoic acid, EET: Epoxyeicosatrienoic acids, HpOTre: hydroperoxy-octadecatrienoic acid, EpODE: Epoxy-octadecadienoic acid, HpOTrE: Hydroperoxy-octadecatrienoic acid, HpEPE: Hydroperoxy-eicosapentaenoic acid, HEPE: hydroxy-eicosapentaenoic acid, DiHEPE: dihydroxy-eicosapentaenoic acid, EpETE: Epoxy-eicosatetraenoic acid, HpDoHE: Hydroperoxy-docosahexaenoic acid, HDoHE: Hydroxy-docosahexaenoic acid, DiHDoHE: Dihydroxy-docosahexaenoic acidEpDPE: Epoxy-docosapentaenoic acid, DiHDPE: Dihydroxy-docosapentaenoic acid.
Figure 2
Figure 2
The role of chronic low-grade inflammation in revealing the relationships between oxylipins and cardiometabolic diseases.
Figure 3
Figure 3
Possible dietary modulation of PUFA-derived oxylipins and their cardiometabolic effects which depends on consumed PUFA types and amounts. PUFAs: Polyunsaturated fatty acids.
Figure 4
Figure 4
The oxylipins and its impact on diabetes. COX: Cyclooxygenase; CYP: Cytochromes P450; HHE: 4-Hydroxy-2-hexenal; HNE: 4-Hydroxy-2-nonenal; LOX: Lipoxygenase; MaR: Maresin; n-3: omega 3 fatty acids; n-6: omega 6 fatty acids; PD/NPD: Protectin/neuroprotectin; PUFA: Polyunsaturated fatty acid; Rv: Resolvin; PUFAs: Polyunsaturated fatty acids.
Figure 5
Figure 5
Functions of oxylipins in vascular control. 20-HETE, 20-hydroxy-5,8,11,14-eicosatetraenoic acid; GPR132, G protein-coupled receptor 132; OxLDL, Oxidized Low-density Lipoprotein;IL-1β, Interleukin-1 beta; FABP4, Fatty Acid-Binding Protein 4; PPARγ, Peroxisome proliferator-activated receptor gamma; ERK1/2, extracellular signal-regulated kinase 1/2; PKC, Protein kinase C; NF-κB, nuclear factor-kappa B; NO, nitric oxide; AGT, Angiotensinogen; ACE, angiotensin-converting enzyme; TNF-α, Tumor necrosis factor alpha; IL-6, Interleukin-6; sEH, soluble epoxide hydrolase enzyme; PI3K, hosphatidylinositol-3 kinase; ICAM-1, intracellular adhesion molecule; VCAM-1, vascular cell adhesion molecule 1 1.
Figure 6
Figure 6
The relationship between NAFLD and oxylipins.
Figure 7
Figure 7
The relationship between CKD and oxylipins.
See this image and copyright information in PMC

References

    1. Wu J.H., Micha R., Mozaffarian D. Dietary fats and cardiometabolic disease: Mechanisms and effects on risk factors and outcomes. Nat. Rev. Cardiol. 2019;16:581–601. doi: 10.1038/s41569-019-0206-1. - DOI - PubMed
    1. Vors C., Le Barz M., Bourlieu C., Michalski M.-C. Dietary lipids and cardiometabolic health: A new vision of structure–activity relationship. Curr. Opin. Clin. Nutr. Metab. Care. 2020;23:451–459. doi: 10.1097/MCO.0000000000000693. - DOI - PubMed
    1. Kapoor B., Kapoor D., Gautam S., Singh R., Bhardwaj S. Dietary polyunsaturated fatty acids (PUFAs): Uses and potential health benefits. Curr. Nutr. Rep. 2021;10:232–242. doi: 10.1007/s13668-021-00363-3. - DOI - PubMed
    1. Eichelmann F., Sellem L., Wittenbecher C., Jäger S., Kuxhaus O., Prada M., Cuadrat R., Jackson K.G., Lovegrove J.A., Schulze M.B. Deep lipidomics in human plasma: Cardiometabolic disease risk and effect of dietary fat modulation. Circulation. 2022;146:21–35. doi: 10.1161/CIRCULATIONAHA.121.056805. - DOI - PMC - PubMed
    1. Kostara C.E. Expanding the Molecular Disturbances of Lipoproteins in Cardiometabolic Diseases: Lessons from Lipidomics. Diagnostics. 2023;13:721. doi: 10.3390/diagnostics13040721. - DOI - PMC - PubMed

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