Oxidation of polyunsaturated fatty acids to produce lipid mediators

Abstract

<jats:title>Abstract</jats:title> <jats:p>The chemistry, biochemistry, pharmacology and molecular biology of oxylipins (defined as a family of oxygenated natural products that are formed from unsaturated fatty acids by pathways involving at least one step of dioxygen-dependent oxidation) are complex and occasionally contradictory subjects that continue to develop at an extraordinarily rapid rate. The term includes docosanoids (e.g. protectins, resolvins and maresins, or specialized pro-resolving mediators), eicosanoids and octadecanoids and plant oxylipins, which are derived from either the omega-6 (n-6) or the omega-3 (n-3) families of polyunsaturated fatty acids. For example, the term eicosanoid is used to embrace those biologically active lipid mediators that are derived from C20 fatty acids, and include prostaglandins, thromboxanes, leukotrienes, hydroxyeicosatetraenoic acids and related oxygenated derivatives. The key enzymes for the production of prostanoids are prostaglandin endoperoxide H synthases (cyclo-oxygenases), while lipoxygenases and oxidases of the cytochrome P450 family produce numerous other metabolites. In plants, the lipoxygenase pathway from C18 polyunsaturated fatty acids yields a variety of important products, especially the jasmonates, which have some comparable structural features and functions. Related oxylipins are produced by non-enzymic means (isoprostanes), while fatty acid esters of hydroxy fatty acids (FAHFA) are now being considered together with the oxylipins from a functional perspective. In all kingdoms of life, oxylipins usually act as lipid mediators through specific receptors, have short half-lives and have functions in innumerable biological contexts.</jats:p>

Omega-3 Polyunsaturated Fatty Acid Intervention Against Established Autoimmunity in a Murine Model of Toxicant-Triggered Lupus

“…DHA and EPA also directly compete with ω-6 PUFAs as enzymatic substrates to specialized pro-resolving mediators (SPMs) (e.g., resolvins, protectins, maresins) ( 62 ) that can impede inflammatory signaling ( 63 , 64 ) and promote efferocytosis which are critical to maintaining immune tolerance ( 63 , 64 ). Germaine to the present study, resolvin D1 and resolvin D2 and maresin 1 can (i) suppress cytokine production by activated CD8 + T cells and CD4 + T helper 1 (TH1) and TH17 cells, (ii) inhibit naïve CD4 + T cell differentiation into TH1 and TH17 cells by GPR32 and ALX/FPR2 receptor-mediated down-regulation of critical transcription factors, and (iii) enhance de novo generation and function of Foxp3 + regulatory T (Treg) cell ( 65 ).…”

Long-Chain Polyunsaturated Fatty Acids (LCPUFAs) and the Developing Immune System: A Narrative Review

“…As a result of these effects, LCPUFAs have been reported to regulate the function of many immune cell types including neutrophils, monocytes, macrophages, dendritic cells, T cells and B cells [ 24 ]. Perhaps the best described function of LCPUFAs with regard to immune function, including the inflammatory component, is their role as substrates for the generation of bioactive lipid mediators [ 25 , 26 ] ( Figure 5 ).…”

“…They can be released upon cell stimulation, typically as a result of the activity of phospholipase A 2 . Once released, LCPUFAs can enter the cyclooxygenase (COX), lipoxygenase (LOX) or cytochrome P450 pathways [ 25 , 26 ]. The COX pathway gives rise to 2-series prostaglandins (PGs) and thromboxanes from AA, and the 5-LOX pathway gives rise to 4-series leukotrienes (LTs).…”

Expert Opinion on Benefits of Long-Chain Omega-3 Fatty Acids (DHA and EPA) in Aging and Clinical Nutrition

“…The second effect of increased EPA and DHA in the membranes of inflammatory cells is that they partially replace the omega-6 PUFA arachidonic acid (see [ 12 , 13 , 14 ] for references). Arachidonic acid is the usual substrate for cyclooxygenase, lipoxygenase and cytochrome P450 enzymes producing eicosanoids [ 37 , 38 ]; these eicosanoids (e.g., prostaglandin E 2 , leukotriene B 4 ) are recognized mediators of inflammation [ 38 ]. Therefore, through the EPA- and DHA-mediated decrease in arachidonic acid availability, production of these inflammatory eicosanoids is decreased (see [ 12 , 13 , 14 ] for references).…”