12-hydroxy-5-8-10-14-eicosatetraenoic-acid and 12-hydroxy-5-8-10-14-17-eicospentaenoic-acid

Lipid bioactivity is a result of direct action and the action of lipid mediators including oxylipins, endocannabinoids, bile acids and steroids. Understanding the factors contributing to biological variation in lipid mediators may inform future approaches to understand and treat complex metabolic diseases. This research aims to determine the contribution of genetic and environmental influences on lipid mediators involved in the regulation of inflammation and energy metabolism. This study recruited 138 monozygotic (MZ) and dizygotic (DZ) twins aged 18-65 years and measured serum oxylipins, endocannabinoids, bile acids and steroids using liquid chromatography mass-spectrometry (LC-MS). In this classic twin design, the similarities and differences between MZ and DZ twins are modelled to estimate the contribution of genetic and environmental influences to variation in lipid mediators. Heritable lipid mediators included the 12-lipoxygenase products 12-hydroxyeicosatetraenoic acid [0.70 (95% CI: 0.12,0.82)], 12-hydroxyeicosatetraenoic acid [0.73 (95% CI: 0.30,0.83)] and 14‑hydroxy-docosahexaenoic acid [0.51 (95% CI: 0.07,0.71)], along with the endocannabinoid docosahexaenoy-lethanolamide [0.52 (95% CI: 0.15,0.72)]. For others such as 13-hydroxyoctadecatrienoic acid and lithocholic acid the contribution of environment to variation was stronger. With increased understanding of lipid mediator functions in health, it is important to understand the factors contributing to their variance. This study provides a comprehensive analysis of lipid mediators and extends pre-existing knowledge of the genetic and environmental influences on the human lipidome.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Adolescent; Adult; Aged; Bile Acids and Salts; Dehydroepiandrosterone; Docosahexaenoic Acids; Eicosapentaenoic Acid; Endocannabinoids; Fatty Acids, Omega-3; Female; Gene-Environment Interaction; Humans; Lipid Metabolism; Male; Middle Aged; Oxylipins; Steroids; Twins, Dizygotic; Twins, Monozygotic; Young Adult

Cardiovascular disease, a major cause of mortality and morbidity, exhibits sexual dimorphism since the onset of cardiovascular disease occurs later in women than in men. The loss of cardioprotection in older women may be due to an increase in arterial stiffness after menopause. Free fatty acid metabolites of polyunsaturated fatty acids, called oxylipins, are known to impact vessel function and may be responsible for the vascular benefits of polyunsaturated fatty acids. The objectives of this study were to compare the plasma oxylipin profiles of young females (20-55 years), older females (55. Higher 12-lipoxygenase oxylipin plasma concentrations associated with lower arterial stiffness in premenopausal females may be an important contributing factor to sex differences in cardiovascular disease. Registration: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01661543, NCT01562171, NCT01890330, NCT02571114 and NCT02317588.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Adult; Age Factors; Aged; Ankle Brachial Index; Biomarkers; Cardiovascular Diseases; Docosahexaenoic Acids; Eicosapentaenoic Acid; Female; Health Status Disparities; Heart Disease Risk Factors; Humans; Male; Menopause; Middle Aged; Obesity; Oxylipins; Pulse Wave Analysis; Risk Assessment; Sex Factors; Up-Regulation; Vascular Stiffness; Young Adult

The eicosanoid generating potential of the brain, gills, skin, ovary, muscle, eye, liver, spleen, heart, and alimentary canal in the rainbow trout, Oncorhynchus mykiss, was examined. All the organs/tissues examined synthesized the 12-lipoxygenase products, 12-hydroxyeicosatetraenoic acid (12-HETE), and 12-hydroxyeicosapentaenoic acid (12-HEPE), implying the widespread nature of this enzyme in trout. Both prostaglandin E and LTC were also found in variable amounts in the organs, with the greatest amount of PGE found in the gill. Leukotriene (LT) B4 and LTB5 were found in supernatants from calcium ionophore-challenged brain, skin, ovary, liver, spleen, and heart, but the lipoxins A4 and A5 were only present in brain, ovary, and spleen in relatively small amounts. As lipoxins have previously been shown to be synthesized by macrophages in rainbow trout [Pettitt et al., J. Biol. Chem. 266, 8720-8726 (1991)], and related cells (microglial cells) are found in the brain of mammals, the localization of macrophage-like cells in trout brain was investigated immunocytochemically. Monoclonal antibodies specific for trout leucocytes failed to identify any microglial-like cells in sections of the brain, although microvessels containing immuno-positive reaction products were observed. A number of distinct lipoxygenase products were found in supernatants of ionophore-challenged gill, including 14-hydroxydocosahexaenoic acid, 12-HETE, and 12-HEPE, and a large number of dihydroxy fatty acid derivatives with conjugated triene chromophores. One of these products was tentatively identified as 8(R),15(S)-dihydroxyeicosatetraenoic acid, a dual 12- and 15-lipoxygenase product, but apparently no LTB4 was generated by this tissue.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Animals; Brain; Captopril; Eicosanoids; Eicosapentaenoic Acid; Fatty Acids; Female; Gills; Hydroxyeicosatetraenoic Acids; Indoles; Leukotriene C4; Masoprocol; Oncorhynchus mykiss; Prostaglandins E; Tissue Distribution; Umbelliferones

Eicosapentaenoic acid (EPA) has been reported to have a potent anti-aggregatory activity and to be efficiently metabolized by 12-lipoxygenase, not by cyclooxygenase in platelets. In vitro effect of 12-lipoxygenase metabolites of EPA on platelet function was studied and compared with those of arachidonic acid (AA). The 12-lipoxygenase metabolites of AA and EPA; 12-hydroperoxyeicosatetraenoic acid (12-HPETE) and 12-hydroperoxyeicosapentaenoic acid (12-HPEPE), and their hydroxy derivatives, 12-hydroxyeicosatetraenoic acid (12-HETE) and 12-hydroxyeicosapentaenoic acid (12-HEPE) were prepared enzymatically using human platelet lysate. These compounds were purified by high performance liquid chromatography and identified by gas chromatography mass spectrometry. 12-HPETE and 12-HPEPE inhibited dose-dependently washed human platelet aggregation and serotonin (5-HT) release induced by AA and collagen. The potency of 12-HPEPE was almost equal to that of 12-HPETE. Their hydroxy derivatives, 12-HETE and 12-HEPE were less potent. 12-hydroperoxy derivatives of AA and EPA were the most potent in inhibiting platelet aggregation and 5-HT release among 5-, 12- and 15-hydroperoxy isomers of AA and EPA. The inhibitory effects of 12-HPETE and 12-HPEPE on platelet aggregation were additive.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Arachidonate Lipoxygenases; Arachidonic Acid; Arachidonic Acids; Blood Platelets; Eicosapentaenoic Acid; Humans; Hydroxyeicosatetraenoic Acids; In Vitro Techniques; Isomerism; Leukotrienes; Lipoxygenase; Platelet Aggregation; Serotonin