Polyunsaturated fatty acids and fatty acid-derived lipid mediators: Recent advances in the understanding of their biosynthesis, structures, and functions

Gomez-Larrauri, 2020, Role of bioactive sphingolipids in physiology and pathology, Essays Biochem, 64, 579, 10.1042/EBC20190091 Hannun, 2008, Principles of bioactive lipid signalling: lessons from sphingolipids, Nat Rev Mol Cell Biol, 9, 139, 10.1038/nrm2329 Shimizu, 2009, Lipid mediators in health and disease: enzymes and receptors as therapeutic targets for the regulation of immunity and inflammation, Annu Rev Pharmacol Toxicol, 49, 123, 10.1146/annurev.pharmtox.011008.145616 Dyall, 2017, Interplay between n-3 and n-6 long-chain polyunsaturated fatty acids and the endocannabinoid system in brain protection and repair, Lipids, 52, 885, 10.1007/s11745-017-4292-8 von Euler, 1983, History and development of prostaglandins, Gen Pharmacol, 14, 3, 10.1016/0306-3623(83)90053-8 Bergstroem, 1964, The Enzymatic Conversion of Essential Fatty Acids into Prostaglandins, J Biol Chem, 239, PC4006-8 Gerwick, 1991, Oxylipin metabolism in the red alga Gracilariopsis lemaneiformis: mechanism of formation of vicinal dihydroxy fatty acids, Arch Biochem Biophys, 290, 436, 10.1016/0003-9861(91)90563-X Phillis, 2006, Cyclooxygenases, lipoxygenases, and epoxygenases in CNS: their role and involvement in neurological disorders, Brain Res Brain Res Rev, 52, 201, 10.1016/j.brainresrev.2006.02.002 Calder, 2020, Eicosanoids, Essays Biochem, 64, 423, 10.1042/EBC20190083 Christie, 2020, Oxidation of polyunsaturated fatty acids to produce lipid mediators, Essays Biochem, 64, 401, 10.1042/EBC20190082 Gabbs, 2015, Advances in Our Understanding of Oxylipins Derived from Dietary PUFAs, Adv Nutr, 6, 513, 10.3945/an.114.007732 Murakami, 2020, Updating phospholipase A2 biology, Biomolecules, 10, 10.3390/biom10101457 Vasquez, 2018, Review of four major distinct types of human phospholipase A2, Adv Biol Regul, 67, 212, 10.1016/j.jbior.2017.10.009 Haeggstrom, 2011, Lipoxygenase and leukotriene pathways: biochemistry, biology, and roles in disease, Chem Rev, 111, 5866, 10.1021/cr200246d Hajeyah, 2020, The biosynthesis of enzymatically oxidized lipids, Front Endocrinol (Lausanne), 11, 10.3389/fendo.2020.591819 Hildreth, 2020, Cytochrome P450-derived linoleic acid metabolites EpOMEs and DiHOMEs: a review of recent studies, J Nutr Biochem, 86, 10.1016/j.jnutbio.2020.108484 Alhouayek, 2014, COX-2-derived endocannabinoid metabolites as novel inflammatory mediators, Trends Pharmacol Sci, 35, 284, 10.1016/j.tips.2014.03.001 Kulmacz, 2003, Comparison of the properties of prostaglandin H synthase-1 and -2, Prog Lipid Res, 42, 377, 10.1016/S0163-7827(03)00023-7 Rouzer, 2009, Cyclooxygenases: structural and functional insights, J Lipid Res, 50, S29, 10.1194/jlr.R800042-JLR200 Kirkby, 2016, Systematic study of constitutive cyclooxygenase-2 expression: role of NF-kappaB and NFAT transcriptional pathways, Proc Natl Acad Sci U S A, 113, 434, 10.1073/pnas.1517642113 Vecchio, 2010, Structural basis of fatty acid substrate binding to cyclooxygenase-2, J Biol Chem, 285, 22152, 10.1074/jbc.M110.119867 Cipollina, 2014, Generation and dietary modulation of anti-inflammatory electrophilic omega-3 fatty acid derivatives, PLoS One, 9, 10.1371/journal.pone.0094836 Groeger, 2010, Cyclooxygenase-2 generates anti-inflammatory mediators from omega-3 fatty acids, Nat Chem Biol, 6, 433, 10.1038/nchembio.367 Davis, 2017, Cytochrome P450 eicosanoids in cerebrovascular function and disease, Pharmacol Ther, 179, 31, 10.1016/j.pharmthera.2017.05.004 Arnold, 2010, Cytochrome P450-dependent metabolism of omega-6 and omega-3 long-chain polyunsaturated fatty acids, Pharmacol Rep, 62, 536, 10.1016/S1734-1140(10)70311-X Holman, 1963, A hypothesis involving competitive inhibitions in the metabolsim of polyunsaturated fatty acids, Acta Chem Scand, 17, S84, 10.3891/acta.chem.scand.17s-0084 Brenna, 2013, Fatty acid analysis by high resolution gas chromatography and mass spectrometry for clinical and experimental applications, Curr Opin Clin Nutr Metab Care, 16, 548, 10.1097/MCO.0b013e328363bc0a Van Pelt, 1999, Acetonitrile chemical ionization tandem mass spectrometry to locate double bonds in polyunsaturated fatty acid methyl esters, Anal Chem, 71, 1981, 10.1021/ac981387f Wang, 2020, Identification of polymethylene-interrupted polyunsaturated fatty acids (PMI-PUFA) by solvent-mediated covalent adduct chemical ionization triple quadrupole tandem mass spectrometry, Anal Chem, 92, 8209, 10.1021/acs.analchem.0c00425 Brenna, 2022, New understandings of the pathway of long-chain polyunsaturated fatty acid biosynthesis, Curr Opin Clin Nutr Metab Care, 25, 60, 10.1097/MCO.0000000000000810 Marquardt, 2000, cDNA cloning, genomic structure, and chromosomal localization of three members of the human fatty acid desaturase family, Genomics, 66, 175, 10.1006/geno.2000.6196 Cho, 1999, Cloning, expression, and fatty acid regulation of the human delta-5 desaturase, J Biol Chem, 274, 37335, 10.1074/jbc.274.52.37335 Cho, 1999, Cloning, expression, and nutritional regulation of the mammalian Delta-6 desaturase, J Biol Chem, 274, 471, 10.1074/jbc.274.1.471 Garcia, 2018, Conversion of dietary trans-vaccenic acid to trans11,cis13-conjugated linoleic acid in the rat lactating mammary gland by Fatty Acid Desaturase 3-catalyzed methyl-end Delta13-desaturation, Biochem Biophys Res Commun, 505, 385, 10.1016/j.bbrc.2018.09.132 Zhang, 2017, Fads3 modulates docosahexaenoic acid in liver and brain, Prostaglandins Leukot Essent Fatty Acids, 123, 25, 10.1016/j.plefa.2017.07.001 Karsai, 2020, FADS3 is a Delta14Z sphingoid base desaturase that contributes to gender differences in the human plasma sphingolipidome, J Biol Chem, 295, 1889, 10.1074/jbc.AC119.011883 Park, 2011, FADS2 function loss at the cancer hotspot 11q13 locus diverts lipid signaling precursor synthesis to unusual eicosanoid fatty acids, PLoS One, 6, 10.1371/journal.pone.0028186 Park, 2018, A rare eicosanoid precursor analogue, sciadonic acid (5Z,11Z,14Z-20:3), detected in vivo in hormone positive breast cancer tissue, Prostaglandins Leukot Essent Fatty Acids, 134, 1, 10.1016/j.plefa.2018.05.002 Pawlosky, 1994, Essential fatty acid metabolism in the feline: relationship between liver and brain production of long-chain polyunsaturated fatty acids, J Lipid Res, 35, 2032, 10.1016/S0022-2275(20)39949-1 Trevizan, 2012, Maintenance of arachidonic acid and evidence of Delta5 desaturation in cats fed gamma-linolenic and linoleic acid enriched diets, Lipids, 47, 413, 10.1007/s11745-011-3651-0 Park, 2018, The role of fatty acid desaturase (FADS) genes in oleic acid metabolism: FADS1 Delta7 desaturates 11-20:1 to 7,11-20:2, Prostaglandins Leukot Essent Fatty Acids, 128, 21, 10.1016/j.plefa.2017.11.004 Wang, 2020, Fatty acid desaturase 2 (FADS2) but not FADS1 desaturates branched chain and odd chain saturated fatty acids, Biochim Biophys Acta Mol Cell Biol Lipids, 1865 Park, 2009, An alternate pathway to long-chain polyunsaturates: the FADS2 gene product Delta8-desaturates 20:2n-6 and 20:3n-3, J Lipid Res, 50, 1195, 10.1194/jlr.M800630-JLR200 Park, 2015, The fatty acid desaturase 2 (FADS2) gene product catalyzes Delta4 desaturation to yield n-3 docosahexaenoic acid and n-6 docosapentaenoic acid in human cells, FASEB J, 29, 3911, 10.1096/fj.15-271783 Oboh, 2017, Two alternative pathways for docosahexaenoic acid (DHA, 22:6n-3) biosynthesis are widespread among teleost fish, Sci Rep, 7, 3889, 10.1038/s41598-017-04288-2 Metherel, 2019, Docosahexaenoic acid is both a product of and a precursor to tetracosahexaenoic acid in the rat, J Lipid Res, 60, 412, 10.1194/jlr.M090373 Park, 2016, Palmitic acid (16:0) competes with omega-6 linoleic and omega-3 a-linolenic acids for FADS2 mediated Delta6-desaturation, Biochim Biophys Acta, 1861, 91, 10.1016/j.bbalip.2015.11.007 Snaebjornsson, 2019, Tumours use a metabolic twist to make lipids, Nature, 566, 333, 10.1038/d41586-019-00352-1 Vriens, 2019, Evidence for an alternative fatty acid desaturation pathway increasing cancer plasticity, Nature, 566, 403, 10.1038/s41586-019-0904-1 Blasbalg, 2011, Changes in consumption of omega-3 and omega-6 fatty acids in the United States during the 20th century, Am J Clin Nutr, 93, 950, 10.3945/ajcn.110.006643 Ramsden, 2012, Lowering dietary linoleic acid reduces bioactive oxidized linoleic acid metabolites in humans, Prostaglandins Leukot Essent Fatty Acids, 87, 135, 10.1016/j.plefa.2012.08.004 Aisen, 1985, Circulating hydroxy fatty acids in familial Mediterranean fever, Proc Natl Acad Sci U S A, 82, 1232, 10.1073/pnas.82.4.1232 Burr, 1929, A new deficiency disease produced by the rigid exclusion of fat from the diet, J Biol Chem, 82, 345, 10.1016/S0021-9258(20)78281-5 Burr, 1930, On the nature and role of the essential fatty acids in nutrition, J Biol Chem, 86, 587, 10.1016/S0021-9258(20)78929-5 Hansen, 1958, Essential fatty acids in infant nutrition. III. Clinical manifestations of linoleic acid deficiency, J Nutr, 66, 565, 10.1093/jn/66.4.565 Holman, 1982, Linolenic acid deficiency in man, Nutr Rev, 40, 144 Bjerve, 1987, Alpha-linolenic acid deficiency in man: effect of essential fatty acids on fatty acid composition, Adv Prostaglandin Thromboxane Leukot Res, 17B, 862 Nakayama, 2006, Prostaglandin E2 promotes degranulation-independent release of MCP-1 from mast cells, J Leukoc Biol, 79, 95, 10.1189/jlb.0405226 Resnik, 1978, Effects of prostaglandins E1, E2, and F2alpha on uterine blood flow in nonpregnant sheep, Am J Physiol, 234, H557 Funk, 1983, Metabolism of linoleic acid by prostaglandin endoperoxide synthase from adult and fetal blood vessels, Biochim Biophys Acta, 754, 57, 10.1016/0005-2760(83)90082-6 Funk, 1985, Release of prostaglandins and monohydroxy and trihydroxy metabolites of linoleic and arachidonic acids by adult and fetal aortae and ductus arteriosus, J Biol Chem, 260, 7481, 10.1016/S0021-9258(17)39632-1 Reinaud, 1989, Oxidative metabolism of linoleic acid by human leukocytes, Biochem Biophys Res Commun, 161, 883, 10.1016/0006-291X(89)92682-X Earles, 1991, Metabolism of oxidized linoleic acid: characterization of 13-hydroxyoctadecadienoic acid dehydrogenase activity from rat colonic tissue, Biochim Biophys Acta, 1081, 174, 10.1016/0005-2760(91)90023-B Sarkar, 2011, Differential effect of amyloid beta on the cytochrome P450 epoxygenase activity in rat brain, Neuroscience, 194, 241, 10.1016/j.neuroscience.2011.07.058 Wendell, 2015, 15-Hydroxyprostaglandin dehydrogenase generation of electrophilic lipid signaling mediators from hydroxy omega-3 fatty acids, J Biol Chem, 290, 5868, 10.1074/jbc.M114.635151 Ozawa, 1986, Biosynthesis of leukotoxin, 9,10-epoxy-12 octadecenoate, by leukocytes in lung lavages of rat after exposure to hyperoxia, Biochem Biophys Res Commun, 134, 1071, 10.1016/0006-291X(86)90360-8 Kuhn, 1990, Occurrence of 9- and 13-keto-octadecadienoic acid in biological membranes oxygenated by the reticulocyte lipoxygenase, Arch Biochem Biophys, 279, 218, 10.1016/0003-9861(90)90484-G Yu, 2019, Soluble epoxide hydrolase-derived linoleic acid oxylipins in serum are associated with periventricular white matter hyperintensities and vascular cognitive impairment, Transl Stroke Res, 10, 522, 10.1007/s12975-018-0672-5 Kumar, 2016, 15-Lipoxygenase metabolites of alpha-linolenic acid, [13-(S)-HPOTrE and 13-(S)-HOTrE], mediate anti-inflammatory effects by inactivating NLRP3 inflammasome, Sci Rep, 6, 31649, 10.1038/srep31649 Bartov, 1980, Susceptibility of chicks to nutritional encephalopathy: effect of fat and alpha-tocopherol content of the breeder diet, Poult Sci, 59, 264, 10.3382/ps.0590264 Dam, 1958, Influence of linoleic and linolenic acids on symptoms of vitamin E deficiency in chicks, Nature, 182, 802, 10.1038/182802a0 Fischer, 1973, Cerebrovascular changes in tocopherol-depleted chicks, fed linoleic acid, J Neuropathol Exp Neurol, 32, 474, 10.1097/00005072-197307000-00011 Kokatnur, 1960, Effect of long chain keto acids on encephalomalacia in chicks, Proc Soc Exp Biol Med, 104, 170, 10.3181/00379727-104-25768 Budowski, 1979, Lipid oxidation products and chick nutritional encephalopathy, Lipids, 14, 768, 10.1007/BF02533514 Moghaddam, 1997, Bioactivation of leukotoxins to their toxic diols by epoxide hydrolase, Nat Med, 3, 562, 10.1038/nm0597-562 Zheng, 2001, Leukotoxin-diol: a putative toxic mediator involved in acute respiratory distress syndrome, Am J Respir Cell Mol Biol, 25, 434, 10.1165/ajrcmb.25.4.4104 Alsalem, 2013, The contribution of the endogenous TRPV1 ligands 9-HODE and 13-HODE to nociceptive processing and their role in peripheral inflammatory pain mechanisms, Br J Pharmacol, 168, 1961, 10.1111/bph.12092 Zheng, 2011, Lipoxygenases mediate the effect of essential fatty acid in skin barrier formation: a proposed role in releasing omega-hydroxyceramide for construction of the corneocyte lipid envelope, J Biol Chem, 286, 24046, 10.1074/jbc.M111.251496 Buchanan, 1985, 13-Hydroxyoctadecadienoic acid is the vessel wall chemorepellant factor, LOX, J Biol Chem, 260, 16056, 10.1016/S0021-9258(17)36198-7 DeMar, 2006, Brain elongation of linoleic acid is a negligible source of the arachidonate in brain phospholipids of adult rats, Biochim Biophys Acta, 1761, 1050, 10.1016/j.bbalip.2006.06.006 Zhang, 2021, Linoleic acid-derived 13-hydroxyoctadecadienoic acid is absorbed and incorporated into rat tissues, Biochim Biophys Acta Mol Cell Biol Lipids, 1866 Taha, 2018, Regulation of rat plasma and cerebral cortex oxylipin concentrations with increasing levels of dietary linoleic acid, Prostaglandins Leukot Essent Fatty Acids, 138, 71, 10.1016/j.plefa.2016.05.004 Hennebelle, 2019, Brain oxylipin concentrations following hypercapnia/ischemia: effects of brain dissection and dissection time, J Lipid Res, 60, 671, 10.1194/jlr.D084228 Hennebelle, 2017, Linoleic acid participates in the response to ischemic brain injury through oxidized metabolites that regulate neurotransmission, Sci Rep, 7, 4342, 10.1038/s41598-017-02914-7 Hennebelle, 2020, Linoleic acid-derived metabolites constitute the majority of oxylipins in the rat pup brain and stimulate axonal growth in primary rat cortical neuron-glia co-cultures in a sex-dependent manner, J Neurochem, 152, 195, 10.1111/jnc.14818 Serhan, 1997, Lipoxins and novel aspirin-triggered 15-epi-lipoxins (ATL): a jungle of cell-cell interactions or a therapeutic opportunity?, Prostaglandins, 53, 107, 10.1016/S0090-6980(97)00001-4 Serhan, 2005, Lipoxins and aspirin-triggered 15-epi-lipoxins are the first lipid mediators of endogenous anti-inflammation and resolution, Prostaglandins Leukot Essent Fatty Acids, 73, 141, 10.1016/j.plefa.2005.05.002 Serhan, 2007, Resolution phase of inflammation: novel endogenous anti-inflammatory and proresolving lipid mediators and pathways, Annu Rev Immunol, 25, 101, 10.1146/annurev.immunol.25.022106.141647 Serhan, 1994, Lipoxin biosynthesis and its impact in inflammatory and vascular events, Biochim Biophys Acta, 1212, 1, 10.1016/0005-2760(94)90185-6 Serhan, 2014, Pro-resolving lipid mediators are leads for resolution physiology, Nature, 510, 92, 10.1038/nature13479 Serhan, 2000, Novel functional sets of lipid-derived mediators with antiinflammatory actions generated from omega-3 fatty acids via cyclooxygenase 2-nonsteroidal antiinflammatory drugs and transcellular processing, J Exp Med, 192, 1197, 10.1084/jem.192.8.1197 Libreros, 2020, A new E-series resolvin: RvE4 stereochemistry and function in efferocytosis of inflammation-resolution, Front Immunol, 11 Serhan, 2002, Resolvins: a family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter pro-inflammation signals, J Exp Med, 196, 1025, 10.1084/jem.20020760 Hong, 2003, Novel docosatrienes and 17S-resolvins generated from docosahexaenoic acid in murine brain, human blood and glial cells: autacoids in anti-inflammation, J Biol Chem, 278, 14677, 10.1074/jbc.M300218200 Serhan, 2006, Anti-inflammatory actions of neuroprotectin D1/protectin D1 and its natural stereoisomers: assignments of dihydroxy-containing docosatrienes, J Immunol, 176, 1848, 10.4049/jimmunol.176.3.1848 Serhan, 2011, Novel proresolving aspirin-triggered DHA pathway, Chem Biol, 18, 976, 10.1016/j.chembiol.2011.06.008 Serhan, 2009, Maresins: novel macrophage mediators with potent anti-inflammatory and pro-resolving actions, J Exp Med, 206, 15, 10.1084/jem.20081880 Chiang, 2020, Specialized pro-resolving mediator network: an update on production and actions, Essays Biochem, 64, 443, 10.1042/EBC20200018 Serhan, 2015, Protectins and maresins: new pro-resolving families of mediators in acute inflammation and resolution bioactive metabolome, Biochim Biophys Acta, 1851, 397, 10.1016/j.bbalip.2014.08.006 Serhan, 2008, Endogenous pro-resolving and anti-inflammatory lipid mediators: a new pharmacologic genus, Br J Pharmacol, 153, S200, 10.1038/sj.bjp.0707489 Serhan, 2007, Resolution of inflammation: state of the art, definitions and terms, FASEB J, 21, 325, 10.1096/fj.06-7227rev Serhan, 2017, Discovery of specialized pro-resolving mediators marks the dawn of resolution physiology and pharmacology, Mol Aspects Med, 58, 1, 10.1016/j.mam.2017.03.001 Fullerton, 2016, Resolution of inflammation: a new therapeutic frontier, Nat Rev Drug Discov, 15, 551, 10.1038/nrd.2016.39 Wei, 2017, The role of pro-resolving lipid mediators in ocular diseases, Mol Aspects Med, 58, 37, 10.1016/j.mam.2017.03.006 Fredman, 2017, Specialized pro-resolving mediators in cardiovascular diseases, Mol Aspects Med, 58, 65, 10.1016/j.mam.2017.02.003 Perretti, 2017, Immune resolution mechanisms in inflammatory arthritis, Nat Rev Rheumatol, 13, 87, 10.1038/nrrheum.2016.193 Jones, 2016, The role of neutrophils in inflammation resolution, Semin Immunol, 28, 137, 10.1016/j.smim.2016.03.007 Serhan, 2018, Cutting edge: human vagus produces specialized pro-resolving mediators of inflammation with electrical stimulation reducing pro-inflammatory eicosanoids, J Immunol, 201, 3161, 10.4049/jimmunol.1800806 Souza, 2020, Enriched marine oil supplements increase peripheral blood specialized pro-resolving mediators concentrations and reprogram host immune responses: a randomized double-blind placebo-controlled study, Circ Res, 126, 75, 10.1161/CIRCRESAHA.119.315506 Colas, 2019, Proresolving mediator profiles in cerebrospinal fluid are linked with disease severity and outcome in adults with tuberculous meningitis, FASEB J, 33, 13028, 10.1096/fj.201901590R Kooij, 2020, Specialized pro-resolving lipid mediators are differentially altered in peripheral blood of patients with multiple sclerosis and attenuate monocyte and blood-brain barrier dysfunction, Haematologica, 105, 2056, 10.3324/haematol.2019.219519 Sano, 2020, Activation of inflammation and resolution pathways of lipid mediators in synovial fluid from patients with severe rheumatoid arthritis compared with severe osteoarthritis, Asia Pac Allergy, 10, 10.5415/apallergy.2020.10.e21 Archambault, 2021, High levels of eicosanoids and docosanoids in the lungs of intubated COVID-19 patients, FASEB J, 35, 10.1096/fj.202100540R Schwarz, 2021, Cutting edge: severe SARS-CoV-2 infection in humans is defined by a shift in the serum lipidome, resulting in dysregulation of eicosanoid immune mediators, J Immunol, 206, 329, 10.4049/jimmunol.2001025 Koenis, 2021, Disrupted resolution mechanisms favor altered phagocyte responses in Covid-19, Circ Res, 10.1161/CIRCRESAHA.121.319142 Chiang, 2017, Structural elucidation and physiologic functions of specialized pro-resolving mediators and their receptors, Mol Aspects Med, 58, 114, 10.1016/j.mam.2017.03.005 Laguna-Fernandez, 2018, ERV1/ChemR23 signaling protects against atherosclerosis by modifying oxidized low-density lipoprotein uptake and phagocytosis in macrophages, Circulation, 138, 1693, 10.1161/CIRCULATIONAHA.117.032801 Artiach, 2020, Omega-3 Polyunsaturated Fatty Acids Decrease Aortic Valve Disease through the Resolvin E1 and ChemR23 Axis, Circulation, 142, 776, 10.1161/CIRCULATIONAHA.119.041868 Trilleaud, 2021, Agonist anti-ChemR23 mAb reduces tissue neutrophil accumulation and triggers chronic inflammation resolution, Sci Adv, 7, 10.1126/sciadv.abd1453 Zhang, 2019, GPR18 expression on PMNs as biomarker for outcome in patient with sepsis, Life Sci, 217, 49, 10.1016/j.lfs.2018.11.061 Jundi, 2021, Inflammation resolution circuits are uncoupled in acute sepsis and correlate with clinical severity, JCI Insight, 10.1172/jci.insight.148866 Sulciner, 2018, Resolvins suppress tumor growth and enhance cancer therapy, J Exp Med, 215, 115, 10.1084/jem.20170681 Hellmann, 2018, Biosynthesis of D-series resolvins in skin provides insights into their role in tissue repair, J Invest Dermatol, 138, 2051, 10.1016/j.jid.2018.03.1498 Giannakis, 2019, Dynamic changes to lipid mediators support transitions among macrophage subtypes during muscle regeneration, Nat Immunol, 20, 626, 10.1038/s41590-019-0356-7 Inoue, 2018, Resolvin D2 limits secondary tissue necrosis after burn wounds in rats, J Burn Care Res, 39, 423 Cherpokova, 2019, Resolvin D4 attenuates the severity of pathological thrombosis in mice, Blood, 134, 1458, 10.1182/blood.2018886317 Chiang, 2012, Infection regulates pro-resolving mediators that lower antibiotic requirements, Nature, 484, 524, 10.1038/nature11042 Luo, 2019, Resolvin D5 inhibits neuropathic and inflammatory pain in male but not female mice: distinct actions of D-series resolvins in chemotherapy-induced peripheral neuropathy, Front Pharmacol, 10, 745, 10.3389/fphar.2019.00745 Levy, 2007, Protectin D1 is generated in asthma and dampens airway inflammation and hyperresponsiveness, J Immunol, 178, 496, 10.4049/jimmunol.178.1.496 Mukherjee, 2004, Neuroprotectin D1: a docosahexaenoic acid-derived docosatriene protects human retinal pigment epithelial cells from oxidative stress, Proc Natl Acad Sci U S A, 101, 8491, 10.1073/pnas.0402531101 Lukiw, 2005, A role for docosahexaenoic acid-derived neuroprotectin D1 in neural cell survival and Alzheimer disease, J Clin Invest, 115, 2774, 10.1172/JCI25420 Zhao, 2011, Docosahexaenoic acid-derived neuroprotectin D1 induces neuronal survival via secretase- and PPARgamma-mediated mechanisms in Alzheimer's disease models, PLoS One, 6, 10.1371/journal.pone.0015816 Marcheselli, 2003, Novel docosanoids inhibit brain ischemia-reperfusion-mediated leukocyte infiltration and pro-informatory gene expression, J Biol Chem, 278, 43807, 10.1074/jbc.M305841200 Schwab, 2007, Resolvin E1 and protectin D1 activate inflammation-resolution programmes, Nature, 447, 869, 10.1038/nature05877 Berg, 2019, Brain tissue saving effects by single-dose intralesional administration of Neuroprotectin D1 on experimental focal penetrating brain injury in rats, J Clin Neurosci, 64, 227, 10.1016/j.jocn.2019.03.032 Bang, 2018, GPR37 regulates macrophage phagocytosis and resolution of inflammatory pain, J Clin Invest, 128, 3568, 10.1172/JCI99888 Bang, 2021, Activation of GPR37 in macrophages confers protection against infection-induced sepsis and pain-like behaviour in mice, Nat Commun, 12, 1704, 10.1038/s41467-021-21940-8 Chen, 2011, Poxytrins, a class of oxygenated products from polyunsaturated fatty acids, potently inhibit blood platelet aggregation, FASEB J, 25, 382, 10.1096/fj.10-161836 White, 2014, Protectin DX alleviates insulin resistance by activating a myokine-liver glucoregulatory axis, Nat Med, 20, 664, 10.1038/nm.3549 Perazza, 2021, Fish oil replacement prevents, while docosahexaenoic acid-derived protectin DX mitigates end-stage-renal-disease in atherosclerotic diabetic mice, FASEB J, 35, 10.1096/fj.202100073R Imai, 2015, Role of omega-3 PUFA-derived mediators, the protectins, in influenza virus infection, Biochim Biophys Acta, 1851, 496, 10.1016/j.bbalip.2015.01.006 Morita, 2013, The lipid mediator protectin D1 inhibits influenza virus replication and improves severe influenza, Cell, 153, 112, 10.1016/j.cell.2013.02.027 Deng, 2014, Maresin biosynthesis and identification of maresin 2, a new anti-inflammatory and pro-resolving mediator from human macrophages, PLoS One, 9, 10.1371/journal.pone.0102362 Chiang, 2019, Maresin 1 activates LGR6 receptor promoting phagocyte immunoresolvent functions, J Clin Invest, 129, 5294, 10.1172/JCI129448 Elder, 2021, Maresin 1 activates LGR6 signaling to inhibit smooth muscle cell activation and attenuate murine abdominal aortic aneurysm formation, FASEB J, 35, 10.1096/fj.202100484R Khedgikar, 2022, Mouse LGR6 regulates osteogenesis in vitro and in vivo through differential ligand use, Bone, 155, 10.1016/j.bone.2021.116267 Han, 2019, A maresin 1/RORalpha/12-lipoxygenase autoregulatory circuit prevents inflammation and progression of nonalcoholic steatohepatitis, J Clin Invest, 130, 1684, 10.1172/JCI124219 Dalli, 2014, Identification of sulfido-conjugated mediators that promote resolution of infection and organ protection, Proc Natl Acad Sci U S A, 111, E4753, 10.1073/pnas.1415006111 Serhan, 2018, New pro-resolving n-3 mediators bridge resolution of infectious inflammation to tissue regeneration, Mol Aspects Med, 64, 1, 10.1016/j.mam.2017.08.002 de la Rosa, 2018, Identification and complete stereochemical assignments of the new Resolvin Conjugates in Tissue Regeneration (RCTR) in human tissues that stimulate proresolving phagocyte functions and tissue regeneration, Am J Pathol, 188, 950, 10.1016/j.ajpath.2018.01.004 Chiang, 2021, Cysteinyl-specialized proresolving mediators link resolution of infectious inflammation and tissue regeneration via TRAF3 activation, Proc Natl Acad Sci U S A, 118, 10.1073/pnas.2013374118 Sansbury, 2021, PCTR1 enhances repair and bacterial clearance in skin wounds, Am J Pathol, 191, 1049, 10.1016/j.ajpath.2021.02.015 Lee, 2015, Resolvin infectious inflammation by targeting the host response, N Engl J Med, 373, 2183, 10.1056/NEJMcibr1511280 Rajasagi, 2011, Controlling herpes simplex virus-induced ocular inflammatory lesions with the lipid-derived mediator resolvin E1, J Immunol, 186, 1735, 10.4049/jimmunol.1003456 Wang, 2017, Aspirin-triggered resolvin D1 reduces pneumococcal lung infection and inflammation in a viral and bacterial coinfection pneumonia model, Clin Sci (Lond), 131, 2347, 10.1042/CS20171006 Recchiuti, 2021, Resolvin D1 and D2 reduce SARS-CoV-2-induced inflammatory responses in cystic fibrosis macrophages, FASEB J, 35, 10.1096/fj.202001952R Ackermann, 2020, Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19, N Engl J Med, 383, 120, 10.1056/NEJMoa2015432 Merad, 2020, Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages, Nat Rev Immunol, 20, 355, 10.1038/s41577-020-0331-4 Nathan, 2020, Neutrophils and COVID-19: Nots, NETs, and knots, J Exp Med, 217, 10.1084/jem.20201439 Dyall, 2015, Long-chain omega-3 fatty acids and the brain: a review of the independent and shared effects of EPA, DPA and DHA, Front Aging Neurosci, 7 Lemaitre, 2011, Genetic loci associated with plasma phospholipid n-3 fatty acids: a meta-analysis of genome-wide association studies from the CHARGE Consortium, PLoS Genet, 7, 10.1371/journal.pgen.1002193 Dalli, 2013, Novel n-3 immunoresolvents: structures and actions, Sci Rep, 3, 1940, 10.1038/srep01940 Dalli, 2015, Elucidation of novel 13-series resolvins that increase with atorvastatin and clear infections, Nat Med, 21, 1071, 10.1038/nm.3911 Colas, 2018, Impaired production and diurnal regulation of vascular rvdn-3 dpa increase systemic inflammation and cardiovascular disease, Circ Res, 122, 855, 10.1161/CIRCRESAHA.117.312472 Sakata, 1992, Circadian fluctuations of tissue plasminogen activator antigen and plasminogen activator inhibitor-1 antigens in vasospastic angina, Am Heart J, 124, 854, 10.1016/0002-8703(92)90964-W Flak, 2020, GPR101 mediates the pro-resolving actions of RvD5n-3 DPA in arthritis and infections, J Clin Invest, 130, 359, 10.1172/JCI131609 Flak, 2019, Inflammatory arthritis disrupts gut resolution mechanisms, promoting barrier breakdown by Porphyromonas gingivalis, JCI Insight, 4, 10.1172/jci.insight.125191 Zhou, 2019, Fibrinogen-like protein 2 controls sepsis catabasis by interacting with resolvin Dp5, Sci Adv, 5, eaax0629, 10.1126/sciadv.aax0629 Lei, 2021, Dabigatran activates inflammation resolution by promoting fibrinogen-like protein 2 shedding and RvD5n-3 DPA production, Theranostics, 11, 4251, 10.7150/thno.50182 Walker, 2017, 13-Series resolvins mediate the leukocyte-platelet actions of atorvastatin and pravastatin in inflammatory arthritis, FASEB J, 31, 3636, 10.1096/fj.201700268 Frigerio, 2018, n-3 Docosapentaenoic acid-derived protectin D1 promotes resolution of neuroinflammation and arrests epileptogenesis, Brain, 141, 3130 Mikroulis, 2022, Lipid mediator n-3 docosapentaenoic acid-derived protectin D1 enhances synaptic inhibition of hippocampal principal neurons by interaction with a G-protein-coupled receptor, FASEB J, 36, 10.1096/fj.202101815R Marques, 2021, Loss of 15-lipoxygenase disrupts Treg differentiation altering their pro-resolving functions, Cell Death Differ, 28, 3140, 10.1038/s41418-021-00807-x Pistorius, 2018, PDn-3 DPA Pathway Regulates Human Monocyte Differentiation and Macrophage Function, Cell Chem Biol, 25, 10.1016/j.chembiol.2018.04.017 Markworth, 2016, Divergent shifts in lipid mediator profile following supplementation with n-3 docosapentaenoic acid and eicosapentaenoic acid, FASEB J, 30, 3714, 10.1096/fj.201600360R Schaller, 2020, Treatment with a marine oil supplement alters lipid mediators and leukocyte phenotype in healthy patients and those with peripheral artery disease, J Am Heart Assoc, 9, 10.1161/JAHA.120.016113 Souza, 2020, Enriched marine oil supplements increase peripheral blood specialized pro-resolving mediators concentrations and reprogram host immune responses: a randomized double-blind placebo-controlled study, Circ Res, 126, 75, 10.1161/CIRCRESAHA.119.315506 Bazan, 2021, Overview of how N32 and N34 elovanoids sustain sight by protecting retinal pigment epithelial cells and photoreceptors, J Lipid Res, 62, 10.1194/jlr.TR120001137 Bazan, 2011, Docosahexaenoic acid signalolipidomics in nutrition: significance in aging, neuroinflammation, macular degeneration, Alzheimer’s, and other neurodegenerative diseases, Annu Rev Nutr, 31, 321, 10.1146/annurev.nutr.012809.104635 Sherry, 2017, Distribution of ELOVL4 in the developing and adult mouse brain, Front Neuroanat, 11, 38, 10.3389/fnana.2017.00038 Sandhoff, 2010, Very long chain sphingolipids: tissue expression, function and synthesis, FEBS Lett, 584, 1907, 10.1016/j.febslet.2009.12.032 Yeboah, 2021, Very long chain fatty acid-containing lipids: a decade of novel insights from the study of ELOVL4, J Lipid Res, 62, 10.1016/j.jlr.2021.100030 Agbaga, 2010, Retinal very long-chain PUFAs: new insights from studies on ELOVL4 protein, J Lipid Res, 51, 1624, 10.1194/jlr.R005025 Bernstein, 2001, Diverse macular dystrophy phenotype caused by a novel complex mutation in the ELOVL4 gene, Invest Ophthalmol Vis Sci, 42, 3331 Zhang, 2001, A 5-bp deletion in ELOVL4 is associated with two related forms of autosomal dominant macular dystrophy, Nat Genet, 27, 89, 10.1038/83817 McMahon, 2007, A Stargardt disease-3 mutation in the mouse Elovl4 gene causes retinal deficiency of C32-C36 acyl phosphatidylcholines, FEBS Lett, 581, 5459, 10.1016/j.febslet.2007.10.050 Agbaga, 2008, Role of Stargardt-3 macular dystrophy protein (ELOVL4) in the biosynthesis of very long chain fatty acids, Proc Natl Acad Sci U S A, 105, 12843, 10.1073/pnas.0802607105 Sangiovanni, 2009, Am J Clin Nutr, 90, 1601, 10.3945/ajcn.2009.27594 Aldahmesh, 2011, Recessive mutations in ELOVL4 cause ichthyosis, intellectual disability, and spastic quadriplegia, Am J Hum Genet, 89, 745, 10.1016/j.ajhg.2011.10.011 Jun, 2017, Elovanoids are novel cell-specific lipid mediators necessary for neuroprotective signaling for photoreceptor cell integrity, Sci Rep, 7, 5279, 10.1038/s41598-017-05433-7 Bhattacharjee, 2017, Elovanoids are a novel class of homeostatic lipid mediators that protect neural cell integrity upon injury, Sci Adv, 3, 10.1126/sciadv.1700735 Bazan, 2018, Docosanoids and elovanoids from omega-3 fatty acids are pro-homeostatic modulators of inflammatory responses, cell damage and neuroprotection, Mol Aspects Med, 64, 18, 10.1016/j.mam.2018.09.003 Rice, 2015, Adiponectin receptor 1 conserves docosahexaenoic acid and promotes photoreceptor cell survival, Nat Commun, 6, 6228, 10.1038/ncomms7228 Aveldano, 1988, Phospholipid species containing long and very long polyenoic fatty acids remain with rhodopsin after hexane extraction of photoreceptor membranes, Biochemistry, 27, 1229, 10.1021/bi00404a024 Gordon, 1990, Docosahexaenoic acid utilization during rod photoreceptor cell renewal, J Neurosci, 10, 2190, 10.1523/JNEUROSCI.10-07-02190.1990 Gordon, 1993, Visualization of [3H]docosahexaenoic acid trafficking through photoreceptors and retinal pigment epithelium by electron microscopic autoradiography, Invest Ophthalmol Vis Sci, 34, 2402 Rodriguez de Turco, 1991, Rapid and selective uptake, metabolism, and cellular distribution of docosahexaenoic acid among rod and cone photoreceptor cells in the frog retina, J Neurosci, 11, 3667, 10.1523/JNEUROSCI.11-11-03667.1991 Do, 2019, Elovanoids counteract oligomeric beta-amyloid-induced gene expression and protect photoreceptors, Proc Natl Acad Sci U S A, 116, 24317, 10.1073/pnas.1912959116 Serhan, 2006, Anti-inflammatory actions of neuroprotectin D1/protectin D1 and its natural stereoisomers: assignments of dihydroxy-containing docosatrienes, J Immunol, 176, 1848, 10.4049/jimmunol.176.3.1848 Shi, 2016, Normobaric oxygen treatment in acute ischemic stroke: a clinical perspective, Med Gas Res, 6, 147, 10.4103/2045-9912.191360 Bazan, 2012, Novel aspirin-triggered neuroprotectin D1 attenuates cerebral ischemic injury after experimental stroke, Exp Neurol, 236, 122, 10.1016/j.expneurol.2012.04.007 Posada-Duque, 2014, Protection after stroke: cellular effectors of neurovascular unit integrity, Front Cell Neurosci, 8, 231, 10.3389/fncel.2014.00231 Moskowitz, 2010, The science of stroke: mechanisms in search of treatments, Neuron, 67, 181, 10.1016/j.neuron.2010.07.002 Panickar, 2005, Astrocytes in cerebral ischemic injury: morphological and general considerations, Glia, 50, 287, 10.1002/glia.20181 Musi, 2018, Tau protein aggregation is associated with cellular senescence in the brain, Aging Cell, 17, 10.1111/acel.12840 Das, 2015, Astrocytes show reduced support of motor neurons with aging that is accelerated in a rodent model of ALS, Neurobiol Aging, 36, 1130, 10.1016/j.neurobiolaging.2014.09.020 Lunyak, 2017, Mesenchymal stem cells secretory responses: senescence messaging secretome and immunomodulation perspective, Front Genet, 8, 220, 10.3389/fgene.2017.00220 Campisi, 2019, From discoveries in ageing research to therapeutics for healthy ageing, Nature, 571, 183, 10.1038/s41586-019-1365-2 He, 2017, Senescence in health and disease, Cell, 169, 1000, 10.1016/j.cell.2017.05.015 Baker, 2016, Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan, Nature, 530, 184, 10.1038/nature16932 Leung, 2022, Alpha-linolenic acid, phytoprostanes and phytofurans in plant, algae and food Galano, 2018, Biological activities of non-enzymatic oxygenated metabolites of polyunsaturated fatty acids (NEO-PUFAs) derived from EPA and DHA: new anti-arrhythmic compounds?, Mol Aspects Med, 64, 161, 10.1016/j.mam.2018.03.003 Galano, 2017, Isoprostanes, neuroprostanes and phytoprostanes: an overview of 25years of research in chemistry and biology, Prog Lipid Res, 68, 83, 10.1016/j.plipres.2017.09.004 Ahmed, 2020, Moving forward with isoprostanes, neuroprostanes and phytoprostanes: where are we now?, Essays Biochem, 64, 463, 10.1042/EBC20190096 Gutteridge, 1990, The measurement and mechanism of lipid peroxidation in biological systems, Trends Biochem Sci, 15, 129, 10.1016/0968-0004(90)90206-Q Morrow, 1990, A series of prostaglandin F2-like compounds are produced in vivo in humans by a non-cyclooxygenase, free radical-catalyzed mechanism, Proc Natl Acad Sci U S A, 87, 9383, 10.1073/pnas.87.23.9383 Kadiiska, 2005, Biomarkers of oxidative stress study II: are oxidation products of lipids, proteins, and DNA markers of CCl4 poisoning?, Free Radic Biol Med, 38, 698, 10.1016/j.freeradbiomed.2004.09.017 Yin, 2011, Free radical lipid peroxidation: mechanisms and analysis, Chem Rev, 111, 5944, 10.1021/cr200084z Jahn, 2008, Beyond prostaglandins--chemistry and biology of cyclic oxygenated metabolites formed by free-radical pathways from polyunsaturated fatty acids, Angew Chem Int Ed Engl, 47, 5894, 10.1002/anie.200705122 Yin, 2007, Urinary prostaglandin F2alpha is generated from the isoprostane pathway and not the cyclooxygenase in humans, J Biol Chem, 282, 329, 10.1074/jbc.M608975200 Porter, 1984, Peroxymercuration-demercuraton of lipid hydroperoxides, Tetrahedron Lett, 25, 807, 10.1016/S0040-4039(01)80032-0 Morrow, 1994, Free radical-induced generation of isoprostanes in vivo. Evidence for the formation of D-ring and E-ring isoprostanes, J Biol Chem, 269, 4317, 10.1016/S0021-9258(17)41781-9 Gao, 2003, Formation of prostaglandins E2 and D2 via the isoprostane pathway: a mechanism for the generation of bioactive prostaglandins independent of cyclooxygenase, J Biol Chem, 278, 28479, 10.1074/jbc.M303984200 Chen, 1999, Formation of reactive cyclopentenone compounds in vivo as products of the isoprostane pathway, J Biol Chem, 274, 10863, 10.1074/jbc.274.16.10863 Hardy, 2011, Nonenzymatic free radical-catalyzed generation of 15-deoxy-Delta(12,14)-prostaglandin J(2)-like compounds (deoxy-J(2)-isoprostanes) in vivo, J Lipid Res, 52, 113, 10.1194/jlr.M010264 Morrow, 1996, Nonenzymatic free radical-catalyzed generation of thromboxane-like compounds (isothromboxanes) in vivo, J Biol Chem, 271, 23185, 10.1074/jbc.271.38.23185 Watson, 1999, Structural identification of a novel pro-inflammatory epoxyisoprostane phospholipid in mildly oxidized low density lipoprotein, J Biol Chem, 274, 24787, 10.1074/jbc.274.35.24787 Jung, 2003, Studies towards the total synthesis of an epoxy isoprostane phospholipid, a potent activator of endothelial cells, Chem Commun, Camb) (2, 196, 10.1039/b209892j Fessel, 2005, Isofurans: novel products of lipid peroxidation that define the occurrence of oxidant injury in settings of elevated oxygen tension, Antioxid Redox Signal, 7, 202, 10.1089/ars.2005.7.202 Cracowski, 2006, Cardiovascular pharmacology and physiology of the isoprostanes, Fundam Clin Pharmacol, 20, 417, 10.1111/j.1472-8206.2006.00435.x Ting, 2010, Platelet function and Isoprostane biology. Should isoprostanes be the newest member of the orphan-ligand family?, J Biomed Sci, 17, 24, 10.1186/1423-0127-17-24 Morrow, 2006, The isoprostanes - unique products of arachidonate peroxidation: their role as mediators of oxidant stress, Curr Pharm Des, 12, 895, 10.2174/138161206776055985 Janssen, 2004, The pulmonary biology of isoprostanes, Chem Phys Lipids, 128, 101, 10.1016/j.chemphyslip.2003.10.009 Bauer, 2014, Pathophysiology of isoprostanes in the cardiovascular system: implications of isoprostane-mediated thromboxane A2 receptor activation, Br J Pharmacol, 171, 3115, 10.1111/bph.12677 Musiek, 2005, Cyclopentenone isoprostanes inhibit the inflammatory response in macrophages, J Biol Chem, 280, 35562, 10.1074/jbc.M504785200 Lappas, 2007, Antiinflammatory effects of the cyclopentenone isoprostane 15-A(2)-IsoP in human gestational tissues, Free Radic Biol Med, 42, 1791, 10.1016/j.freeradbiomed.2007.03.009 Muri, 2020, Cyclopentenone prostaglandins and structurally related oxidized lipid species instigate and share distinct pro- and anti-inflammatory pathways, Cell Rep, 30, 10.1016/j.celrep.2020.03.019 Bretscher, 2015, Phospholipid oxidation generates potent anti-inflammatory lipid mediators that mimic structurally related pro-resolving eicosanoids by activating Nrf2, EMBO Mol Med, 7, 593, 10.15252/emmm.201404702 Jamil, 2014, Role of the non-enzymatic metabolite of eicosapentaenoic acid, 5-epi-5-F3t-isoprostane in the regulation of [ (3)H]D-aspartate release in isolated bovine retina, Neurochem Res, 39, 2360, 10.1007/s11064-014-1436-6 Brooks, 2011, The fatty acid oxidation product 15-A3t-isoprostane is a potent inhibitor of NFkappaB transcription and macrophage transformation, J Neurochem, 119, 604, 10.1111/j.1471-4159.2011.07422.x Musiek, 2008, Electrophilic cyclopentenone neuroprostanes are anti-inflammatory mediators formed from the peroxidation of the omega-3 polyunsaturated fatty acid docosahexaenoic acid, J Biol Chem, 283, 19927, 10.1074/jbc.M803625200 Majkova, 2011, Omega-3 fatty acid oxidation products prevent vascular endothelial cell activation by coplanar polychlorinated biphenyls, Toxicol Appl Pharmacol, 251, 41, 10.1016/j.taap.2010.11.013 Gladine, 2014, Lipid profiling following intake of the omega 3 fatty acid DHA identifies the peroxidized metabolites F4-neuroprostanes as the best predictors of atherosclerosis prevention, PLoS One, 9, 10.1371/journal.pone.0089393 Roy, 2015, Nonenzymatic lipid mediators, neuroprostanes, exert the antiarrhythmic properties of docosahexaenoic acid, Free Radic Biol Med, 86, 269, 10.1016/j.freeradbiomed.2015.04.014 Signorini, 2021, F4-neuroprostanes: a role in sperm capacitation, Life (Basel), 11 Gladine, 2021, The clinical translation of eicosanoids and other oxylipins, although challenging, should be actively pursued, Adv Clin Lab, 21, 27 Lee, 2020, Nonenzymatic oxygenated metabolite of docosahexaenoic acid, 4(RS)-4-F4t -neuroprostane, acts as a bioactive lipid molecule in neuronal cells, FEBS Lett, 594, 1797, 10.1002/1873-3468.13774 Yore, 2014, Discovery of a class of endogenous mammalian lipids with anti-diabetic and anti-inflammatory effects, Cell, 159, 318, 10.1016/j.cell.2014.09.035 Brejchova, 2020, Understanding FAHFAs: from structure to metabolic regulation, Prog Lipid Res, 79, 10.1016/j.plipres.2020.101053 Smedley, 2002, Mayolenes: labile defensive lipids from the glandular hairs of a caterpillar (Pieris rapae), Proc Natl Acad Sci U S A, 99, 6822, 10.1073/pnas.102165699 Kolar, 2019, Linoleic acid esters of hydroxy linoleic acids are anti-inflammatory lipids found in plants and mammals, J Biol Chem, 294, 10698, 10.1074/jbc.RA118.006956 Pham, 2019, Moose and caribou as novel sources of functional lipids: fatty acid esters of hydroxy fatty acids, diglycerides and monoacetyldiglycerides, Molecules, 24, 10.3390/molecules24020232 Hammarstedt, 2018, Adipose tissue dysfunction is associated with low levels of the novel Palmitic Acid Hydroxystearic Acids, Sci Rep, 8, 15757, 10.1038/s41598-018-34113-3 Paluchova, 2020, Lipokine 5-PAHSA is regulated by adipose triglyceride lipase and primes adipocytes for de novo lipogenesis in mice, Diabetes, 69, 300, 10.2337/db19-0494 Brezinova, 2020, Exercise training induces insulin-sensitizing PAHSAs in adipose tissue of elderly women, Biochim Biophys Acta Mol Cell Biol Lipids, 1865 Dongoran, 2020, Determination of major endogenous FAHFAs in healthy human circulation: the correlations with several circulating cardiovascular-related biomarkers and anti-inflammatory effects on RAW 264.7 cells, Biomolecules, 10, 10.3390/biom10121689 Malý, 2021, Lipidomic analysis to assess oxidative stress in acute coronary syndrome and acute stroke patients, Metabolites, 11, 412, 10.3390/metabo11070412 Zhu, 2017, Highly sensitive determination of fatty acid esters of hydroxyl fatty acids by liquid chromatography-mass spectrometry, J Chromatogr B Analyt Technol Biomed Life Sci, 1061-1062, 34, 10.1016/j.jchromb.2017.06.045 Hu, 2021, Lipidomics revealed aberrant metabolism of lipids including FAHFAs in renal tissue in the progression of lupus nephritis in a murine model, Metabolites, 11, 10.3390/metabo11030142 Gowda, 2020, Chemical labeling assisted detection and identification of short chain fatty acid esters of hydroxy fatty acid in rat colon and cecum contents, Metabolites, 10, 398, 10.3390/metabo10100398 Fais, 2021, Metabolomics and lipid profile analysis of Coccomyxa melkonianii SCCA 048, Extremophiles, 25, 357, 10.1007/s00792-021-01234-z Brezinova, 2018, Levels of palmitic acid ester of hydroxystearic acid (PAHSA) are reduced in the breast milk of obese mothers, Biochim Biophys Acta Mol Cell Biol Lipids, 1863, 126, 10.1016/j.bbalip.2017.11.004 Moreau, 2008, The identification of mono-, di-, tri-, and tetragalactosyl-diacylglycerols and their natural estolides in oat kernels, Lipids, 43, 533, 10.1007/s11745-008-3181-6 Liberati-Cizmek, 2019, Analysis of fatty acid esters of hydroxyl fatty acid in selected plant food, Plant Foods Hum Nutr, 74, 235, 10.1007/s11130-019-00728-8 Matsuzawa, 2021, Food lipidomics for 155 agricultural plant products, J Agric Food Chem, 69, 8981, 10.1021/acs.jafc.0c07356 Kuda, 2018, Nrf2-mediated antioxidant defense and peroxiredoxin 6 are linked to biosynthesis of palmitic acid ester of 9-hydroxystearic acid, Diabetes, 67, 1190, 10.2337/db17-1087 Balas, 2018, Branched fatty acyl esters of hydroxyl fatty acids (FAHFAs), appealing beneficial endogenous fat against obesity and type-2 diabetes, Chemistry, 24, 9463, 10.1002/chem.201800853 Smith, 2016, Adipose tissue regulates insulin sensitivity: role of adipogenesis, de novo lipogenesis and novel lipids, J Intern Med, 280, 465, 10.1111/joim.12540 Vijayakumar, 2017, Absence of carbohydrate response element binding protein in adipocytes causes systemic insulin resistance and impairs glucose transport, Cell Rep, 21, 1021, 10.1016/j.celrep.2017.09.091 Benlebna, 2021, Long-term intake of 9-PAHPA or 9-OAHPA modulates favorably the basal metabolism and exerts an insulin sensitizing effect in obesogenic diet-fed mice, Eur J Nutr, 60, 2013, 10.1007/s00394-020-02391-1 Benlebna, 2020, Long-term high intake of 9-PAHPA or 9-OAHPA increases basal metabolism and insulin sensitivity but disrupts liver homeostasis in healthy mice, J Nutr Biochem, 79, 10.1016/j.jnutbio.2020.108361 Paluchova, 2020, Triacylglycerol-rich oils of marine origin are optimal nutrients for induction of polyunsaturated docosahexaenoic acid ester of hydroxy linoleic acid (13-DHAHLA) with anti-inflammatory properties in mice, Mol Nutr Food Res, 64, 10.1002/mnfr.201901238 Benlebna, 2021, Potential physio-pathological effects of branched fatty acid esters of hydroxy fatty acids, Biochimie, 182, 13, 10.1016/j.biochi.2020.12.020 Gowda, 2020, Identification of short-chain fatty acid esters of hydroxy fatty acids (SFAHFAs) in a murine model by nontargeted analysis using ultra-high-performance liquid chromatography/linear ion trap quadrupole-Orbitrap mass spectrometry, Rapid Commun Mass Spectrom, 34, 10.1002/rcm.8831 Butovich, 2009, Human tear film and meibum. Very long chain wax esters and (O-acyl)-omega-hydroxy fatty acids of meibum, J Lipid Res, 50, 2471, 10.1194/jlr.M900252-JLR200 Butovich, 2019, Effects of sex (or lack thereof) on meibogenesis in mice (Mus musculus): comparative evaluation of lipidomes and transcriptomes of male and female tarsal plates, Ocul Surf, 17, 793, 10.1016/j.jtos.2019.03.002 Wood, 2018, Lipidomics of equine amniotic fluid: Identification of amphiphilic (O-acyl)-ω-hydroxy-fatty acids, Theriogenology, 105, 120, 10.1016/j.theriogenology.2017.09.012 Hirabayashi, 2017, PNPLA1 has a crucial role in skin barrier function by directing acylceramide biosynthesis, Nat Commun, 8, 14609, 10.1038/ncomms14609 Kaluzikova, 2017, Cholesteryl esters of omega-(O-acyl)-hydroxy fatty acids in vernix caseosa, J Lipid Res, 58, 1579, 10.1194/jlr.M075333 Wood, 2016, Lipidomics of equine sperm and seminal plasma: Identification of amphiphilic (O-acyl)-ω-hydroxy-fatty acids, Theriogenology, 86, 1212, 10.1016/j.theriogenology.2016.04.012 Butovich, 2017, Meibomian glands, meibum, and meibogenesis, Exp Eye Res, 163, 2, 10.1016/j.exer.2017.06.020 Miyamoto, 2020, Lipid polarity gradient formed by ω-hydroxy lipids in tear film prevents dry eye disease, eLife, 9, 10.7554/eLife.53582 Brejchova, 2021, Distinct roles of adipose triglyceride lipase and hormone-sensitive lipase in the catabolism of triacylglycerol estolides, Proc Natl Acad Sci U S A, 118, 10.1073/pnas.2020999118 Erikci Ertunc, 2020, AIG1 and ADTRP are endogenous hydrolases of fatty acid esters of hydroxy fatty acids (FAHFAs) in mice, J Biol Chem, 295, 5891, 10.1074/jbc.RA119.012145 Hamberg, 1998, Isolation and structure of a new galactolipid from oat seeds, Lipids, 33, 355, 10.1007/s11745-998-0215-9 Moore, 2016, Sinninghe Damsté, Elucidation and identification of amino acid containing membrane lipids using liquid chromatography/high-resolution mass spectrometry, Rapid Commun Mass Spectrom, 30, 739, 10.1002/rcm.7503 Lynch, 2019, The glycine lipids of bacteroides thetaiotaomicron are important for fitness during growth in vivo and in vitro, Appl Environ Microbiol, 85, 10.1128/AEM.02157-18 Yasutaka, 1976, An ornithine-containing lipid isolated from Gluconobacter cerinus, Biochim Biophysica Acta (BBA) - Lipids Lipid Metabol, 450, 225, 10.1016/0005-2760(76)90094-1 Wood, 2020, Fatty acyl esters of hydroxy fatty acid (FAHFA) lipid families, Metabolites, 10, 10.3390/metabo10120512 Moore, 2021, Trimethylornithine membrane lipids: discovered in planctomycetes and identified in diverse environments, Metabolites, 11, 49, 10.3390/metabo11010049 Tahara, 1976, A New Lipid; the Ornithine and Taurine-containing “Cerilipin”, Agric Biol Chem, 40, 243 Geiger, 2010, Amino acid-containing membrane lipids in bacteria, Prog Lipid Res, 49, 46, 10.1016/j.plipres.2009.08.002 Schneider, 2019, Anti-bacterial effect and cytotoxicity assessment of lipid 430 isolated from Algibacter sp, Molecules, 24, 3991, 10.3390/molecules24213991 Nemati, 2017, Deposition and hydrolysis of serine dipeptide lipids of Bacteroidetes bacteria in human arteries: relationship to atherosclerosis, J Lipid Res, 58, 1999, 10.1194/jlr.M077792 Farrokhi, 2013, Bacterial lipodipeptide, Lipid 654, is a microbiome-associated biomarker for multiple sclerosis, Clin Transl Immunol., 2, 10.1038/cti.2013.11 Mueller, 2008, General detoxification and stress responses are mediated by oxidized lipids through TGA transcription factors in Arabidopsis, Plant Cell, 20, 768, 10.1105/tpc.107.054809 Jiang, 2021, Ferroptosis: mechanisms, biology and role in disease, Nat Rev Mol Cell Biol, 22, 266, 10.1038/s41580-020-00324-8 Shah, 2018, Resolving the role of lipoxygenases in the initiation and execution of ferroptosis, ACS Cent Sci, 4, 387, 10.1021/acscentsci.7b00589 Tang, 2021, Ferroptosis: molecular mechanisms and health implications, Cell Res, 31, 107, 10.1038/s41422-020-00441-1 Lagarde, 2012, Expanding the horizons of lipidomics. Towards fluxolipidomics, Mol Membr Biol, 29, 222, 10.3109/09687688.2012.689378 Simopoulos, 2011, Importance of the omega-6/omega-3 balance in health and disease: evolutionary aspects of diet, World Rev Nutr Diet, 102, 10, 10.1159/000327785 Calder, 2020, Eicosapentaenoic and docosahexaenoic acid derived specialised pro-resolving mediators: Concentrations in humans and the effects of age, sex, disease and increased omega-3 fatty acid intake, Biochimie, 178, 105, 10.1016/j.biochi.2020.08.015 Barden, 2020, Effects of antiemetic doses of dexamethasone on plasma mediators of inflammation resolution and pain after surgery in women, Prostaglandins Other Lipid Mediat, 149, 10.1016/j.prostaglandins.2020.106427 Hartling, 2021, Quantitative profiling of inflammatory and pro-resolving lipid mediators in human adolescents and mouse plasma using UHPLC-MS/MS, Clin Chem Lab Med, 10.1515/cclm-2021-0644 Isopi, 2020, Resolvin D1 reduces lung infection and inflammation activating resolution in cystic fibrosis, Front Immunol, 11, 581, 10.3389/fimmu.2020.00581 Barden, 2021, Increased inspired oxygen concentration does not adversely affect oxidative stress and the resolution of inflammation during reperfusion in patients undergoing knee replacement surgery, Free Radic Res, 55, 131, 10.1080/10715762.2020.1868451 Lee, 2021, Subgingival microbiome and specialized pro-resolving lipid mediator pathway profiles are correlated in periodontal inflammation, Front Immunol, 12 Keeley, 2022, Specialized proresolving mediators in symptomatic women with coronary microvascular dysfunction (from the women's ischemia trial to reduce events in nonobstructive CAD [WARRIOR] trial), Am J Cardiol, 162, 1, 10.1016/j.amjcard.2021.09.015 Vickery, 2021, Altered tissue specialized pro-resolving mediators in chronic rhinosinusitis, Prostaglandins Leukot Essent Fatty Acids, 164, 10.1016/j.plefa.2020.102218 Bazan, 2017, Circulating inflammation-resolving lipid mediators RvD1 and DHA are decreased in patients with acutely symptomatic carotid disease, Prostaglandins Leukot Essent Fatty Acids, 125, 43, 10.1016/j.plefa.2017.08.007 Schulte, 2020, The relationship between specialized pro-resolving lipid mediators, morbid obesity and weight loss after bariatric surgery, Sci Rep, 10, 20128, 10.1038/s41598-020-75353-6 Barden, 2018, The effect of n-3 fatty acids and coenzyme Q10 supplementation on neutrophil leukotrienes, mediators of inflammation resolution and myeloperoxidase in chronic kidney disease, Prostaglandins Other Lipid Mediat, 136, 1, 10.1016/j.prostaglandins.2018.03.002 See, 2017, Effects of prenatal n-3 fatty acid supplementation on offspring resolvins at birth and 12 years of age: a double-blind, randomised controlled clinical trial, Br J Nutr, 118, 971, 10.1017/S0007114517002914 Ramirez, 2019, Fish oil increases specialized pro-resolving lipid mediators in PAD (The OMEGA-PAD II Trial), J Surg Res, 238, 164, 10.1016/j.jss.2019.01.038 Lamon-Fava, 2021, Dose- and time-dependent increase in circulating anti-inflammatory and pro-resolving lipid mediators following eicosapentaenoic acid supplementation in patients with major depressive disorder and chronic inflammation, Prostaglandins Leukot Essent Fatty Acids, 164, 10.1016/j.plefa.2020.102219 So, 2021, EPA and DHA differentially modulate monocyte inflammatory response in subjects with chronic inflammation in part via plasma specialized pro-resolving lipid mediators: a randomized, double-blind, crossover study, Atherosclerosis, 316, 90, 10.1016/j.atherosclerosis.2020.11.018 Welty, 2021, Regression of human coronary artery plaque is associated with a high ratio of (18-hydroxy-eicosapentaenoic acid + resolvin E1) to leukotriene B4, FASEB J, 35, 10.1096/fj.202002471R Mozurkewich, 2016, Pathway markers for pro-resolving lipid mediators in maternal and umbilical cord blood: a secondary analysis of the mothers, omega-3, and mental health study, Front Pharmacol, 7, 274, 10.3389/fphar.2016.00274 Arita, 2005, Stereochemical assignment, antiinflammatory properties, and receptor for the omega-3 lipid mediator resolvin E1, J Exp Med, 201, 713, 10.1084/jem.20042031 Colas, 2014, Identification and signature profiles for pro-resolving and inflammatory lipid mediators in human tissue, Am J Physiol Cell Physiol, 307, C39, 10.1152/ajpcell.00024.2014