Dietary docosahexaenoic and eicosapentaenoic acid: Emerging mediators of inflammation

Abstract

The inflammatory response is designed to help fight and clear infection, remove harmful chemicals, and repair damaged tissue and organ systems. Although this process, in general, is protective, the failure to resolve the inflammation and return the target tissue to homeostasis can result in disease, including the promotion of cancer. A plethora of published literature supports the contention that dietary n-3 polyunsaturated fatty acids (PUFA), and eicosapentaenoic (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) in particular, are important modulators of a host's inflammatory/immune responses. The following review describes a mechanistic model that may explain, in part, the pleiotropic anti-inflammatory and immunosuppressive properties of EPA and DHA. In this review, we focus on salient studies that address three overarching mechanisms of n-3 PUFA action: (i) modulation of nuclear receptor activation, i.e., nuclear factor-κB (NF-κB) suppression; (ii) suppression of arachidonic acid–cyclooxygenase-derived eicosanoids, primarily prostaglandin E2-dependent signaling; and (iii) alteration of the plasma membrane micro-organization (lipid rafts), particularly as it relates to the function of Toll-like receptors (TLRs), and T-lymphocyte signaling molecule recruitment to the immunological synapse (IS). We propose that lipid rafts may be targets for the development of n-3 PUFA-containing dietary bioactive agents to down-modulate inflammatory and immune responses and for the treatment of autoimmune and chronic inflammatory diseases.

Omega-3 long-chain polyunsaturated fatty acids and aquaculture in perspective

“…In brief, inflammatory responses are largely driven by eicosanoids produced from the major n-6 LC-PUFA, ARA, but other LC-PUFA, particularly EPA, compete with ARA at level of the cyclooxygenase (COX) and lipoxygenase enzymes responsible for the production of eicosanoids, both reducing the production of proinflammatory ARA derivatives and producing less inflammatory EPA-derived mediators (Calder, 2007). However, there is considerable research showing a wide range of mechanisms potentially underpinning the effects of n-3 LC-PUFA on inflammatory responses and immune pathways (Chapkin et al, 2009;Calder, 2013). In particular in recent years, it has been established that the n-3 LC-PUFA, EPA and DHA, are also precursors of other COX-2 derived non-classical eicosanoid derivatives called resolvins, maresins and protectins, which are specialized pro-resolving mediators (PSM) that bring about resolution of the inflammatory response and a return to homeostasis (Serhan and Petasis, 2011;Weylandt et al, 2012).…”

“…In particular in recent years, it has been established that the n-3 LC-PUFA, EPA and DHA, are also precursors of other COX-2 derived non-classical eicosanoid derivatives called resolvins, maresins and protectins, which are specialized pro-resolving mediators (PSM) that bring about resolution of the inflammatory response and a return to homeostasis (Serhan and Petasis, 2011;Weylandt et al, 2012). In addition, as ligands of various transcription factors, n-3 LC-PUFA and their derivatives can also have affects on expression of genes in inflammatory and immune pathways (Chapkin et al, 2009;Schmuth et al, 2014). Therefore, n-3 LC-PUFA have a combination of effects acting to reduce the respiratory burst and increase resolution (Calder, 2013).…”

Omega-3 Long-Chain Polyunsaturated Fatty Acids for Extremely Preterm Infants: A Systematic Review

“…Dietary LCPUFA, particularly DHA and eicosapentaenoic acid are important modulators of inflammation. Considering the anti-inflammatory effect of DHA, and of its downstream metabolite eicosanoids, 51,52 authors have argued that DHA deficits in preterm infants may have considerable, underestimated adverse effects during the neonatal period. 9,10,53,54 In light of the strong association between elevated inflammation and both shortand long-term morbidities in extreme preterm infants, 48,55 we postulate that a DHA supplementation or a decrease in the omega-6/omega-3 reduces the occurrence of these major adverse neonatal outcomes, including BPD.…”

Incorporation of n-3 fatty acids by the liver of mice fed linseed oil as a function of feeding duration

“…The competition between n-6 and n-3 FA may be clinically important and may affect the development or progression of diseases (Vancassel et al, 2007). It is worth nothing that AA is important for fetal growth and the metabolism of prostaglandins (Calder, 2006;Innis, 2007), while among LC-PUFA, EPA and DHA have received much attention from the scientific communities because of their positive role in human health (Carl et al, 2009;Calder, 2006;Chapkin et al, 2009). Studies in humans have also demonstrated the conversion of LNA to EPA and DHA (Harnack et al, 2009).…”