Eicosadienoic acid

15-hydroxy eicosadienoic acid is an exacerbating factor for nasal congestion in mice

Allergic rhinitis (AR) is one of the most common allergic inflammatory diseases worldwide. In AR, increased blood flow and vascular permeability in nasal mucosa cause rhinorrhea and nasal congestion. We investigated the role of an 11Z,14Z-eicosadienoic acid-derived metabolite, 15-hydroxy-11Z,13Z-eicosadienoic acid (15-HEDE), in functional changes in vasculature and nasal congestion in AR. Repeated intranasal administration of Ovalbumin (OVA) caused AR symptoms, such as sneezing and nasal congestion, in mice. OVA administration increased the level of 15-HEDE in nasal lavage fluid, which reached approximately 0.6 ng/ml after ten OVA treatments. Upon measuring vascular contraction, treatment with 0.1-3 μM 15-HEDE did not cause contraction in mouse aortae, while it dilated aortae that were pre-contracted by thromboxane receptor stimulation. Pretreatment with the voltage-gated K+ (KV ) channel inhibitor 4-aminopyridine significantly inhibited the 15-HEDE-induced vascular relaxation. Intravital imaging showed that administration of 1 μg 15-HEDE dilated blood vessels, and Mile's assay demonstrated that this administration also caused dye leakage, indicating vascular hyperpermeability in mouse ears. Computed tomography scanning and morphological study revealed that administration of 3 μg 15-HEDE narrowed nasal passages and thickened nasal mucosa in mice. Finally, we confirmed that treating mice with 3 μg 15-HEDE caused rhinitis symptoms, such as abdominal breathing, and reduced respiratory frequency, suggesting nasal congestion. 15-HEDE caused vasodilation by activating KV channels and increased vascular permeability, which may lead to nasal congestion. Furthermore, 15-HEDE might be a new lipid mediator that exacerbates nasal congestion in AR.

Eicosadienoic acid differentially modulates production of pro-inflammatory modulators in murine macrophages

Eicosadienoic acid (Δ11,14-20:2; EDA) is a rare, naturally occurring n-6 polyunsaturated fatty acid (PUFA) found mainly in animal tissues. EDA is elongated from linoleic acid (LA), and can also be metabolized to dihomo-γ-linolenic acid (DGLA), arachidonic acid (AA), and sciadonic acid (Δ5,11,14-20:3; SCA). Although, the metabolism of EDA has been extensively studied, there are few reports regarding how EDA might affect inflammatory processes. The objective of this study was to determine the effect of EDA on the n-6 PUFA composition and inflammatory response of murine RAW264.7 macrophages to lipopolysaccharide (LPS). EDA was taken up rapidly by macrophages and metabolized to SCA, and the percentages of both fatty acids increased in cellular phospholipids in a dose-dependent manner. The incorporation of EDA into macrophage lipids increased the proportions of LA, DGLA, and AA as well, and reduced the proportion of total monounsaturated fatty acids. When LPS were applied to the macrophages, EDA decreased the production of nitric oxide (NO), and increased that of prostaglandin E(2) (PGE(2)) and tumor necrotic factor-α. The modulation of NO and PGE(2) was due, in part, to the modified expression of inducible nitric oxide synthase and type II cyclooxygenase. The differential effects of EDA on pro-inflammatory mediators might attribute to the negative feedback mechanism associated with prolonged inflammation. Furthermore, EDA was a weaker pro-inflammatory agent than LA, and not as anti-inflammatory as SCA. This study shows that EDA can modulate the metabolism of PUFA and alter the responsiveness of macrophages to inflammatory stimulation.

Alterations in Polyunsaturated Fatty Acid Metabolism and Reduced Serum Eicosadienoic Acid Level in Ulcerative Colitis: Is There a Place for Metabolomic Fatty Acid Biomarkers in IBD?

Dietary linoleic acid has no effect on arachidonic acid, but increases n-6 eicosadienoic acid, and lowers dihomo-gamma-linolenic and eicosapentaenoic acid in plasma of adult men

High intakes of linoleic acid (LA,18:2n-6) have raised concern due to possible increase in arachidonic acid (ARA, 20:4n-6) synthesis, and inhibition of alpha linolenic acid (ALA, 18:3n-3) desaturation to eicosapentaenoic (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3). In healthy men, 10.5% energy compared to 3.8% energy LA with 1% energy ALA increased plasma phospholipid LA and 20:2n-6, the elongation product of LA, and decreased EPA, with no change in ARA. However, LA was inversely related to ARA at both 10.5% energy and 3.8% energy LA, (r=-0.761, r=-0.817, p<0.001, respectively). A two-fold variability in ARA among individuals was not explained by the dietary LA, ARA, ALA, or fish intake. Our results confirm LA requirements for ARA synthesis is low, <3.8% energy, and they suggest current LA intakes saturate Delta-6 desaturation and adversely affect n-3 fatty acid metabolism. Factors other than n-6 fatty acid intake are important modifiers of plasma ARA.

Facile syntheses for (5Z,9Z)-5,9-hexadecadienoic acid, (5Z,9Z)-5,9-nonadecadienoic acid, and (5Z,9Z)-5,9-eicosadienoic acid through a common synthetic route

The delta 5,9 fatty acids (5Z,9Z)-5,9-hexadecadienoic acid, (5Z,9Z)-5,9-nonadecadienoic acid, and (5Z,9Z)-5,9-eicosadienoic acid were synthesized for the first time in four steps (9-12% overall yield) starting from commercially available 2-(2-bromoethyl)-1,3-dioxolane. The synthetic approach provided enough material to corroborate the structure and stereochemistry of (5Z,9Z)-5,9-nonadecadienoic acid which was recently identified in the flowers of Malvaviscus arboreus (Malvaceae). The novel phospholipids 1-hexadecanoyl-2-[(5Z,9Z)-5,9-eicosadienoyl]-sn-glycer o-3-phosphocholine and 1-octadecanoyl-2-[(5Z,9Z)-5,9-eicosadienoyl]-sn- glycero-3-phosphocholine were also synthesized from commercially available L-alpha-phosphatidylcholine (egg yolk) and characterized by positive ion electrospray mass spectrometry. These are the first examples of unsymmetrical phospholipids with saturated fatty acids at the sn-1 position and delta 5,9 fatty acids at the sn-2 position.