Effect of dietary supplementation with n-9 eicosatrienoic acid on leukotriene B4 synthesis in rats: A novel approach to inhibition of eicosanoid synthesis

Studies were undertaken to assess the biochemical effects of dietary supplementation with n-9 eicosatrienoic acid (ETrA), an arachidonic acid analogue that is normally present in cell membranes at very low levels but is raised in the presence of essential fatty acid deficiency (EFAD). The incorporation of dietary ETrA into rat neutrophils and its effect on A23187-stimulated 5-lipoxygenase metabolism in these cells was examined; in addition, the effect of ETrA was compared with that of another arachidonic acid analogue, eicosapentaenoic acid (EPA), which is known to accumulate in cell membranes and inhibit synthesis of leukotriene B₄ (LBT₄), a product of the 5-lipoxygenase metabolic pathway. Rats were fed a defined diet that was sufficient in essential fatty acids and that contained EPA or ETrA (0.14% of energy) or no added fatty acid, for 3 wk. In the cells from ETrA-fed rats, LTB₄ synthesis was inhibited relative to control values, but sythesis of the other products of 5-lipoxygenase metabolism, 5-hydroxyeicosatetraenoic acid (5-HETE) and the all-trans isomers of LTB₄, were not inhibited. This pattern indicates inhibition of LTA hydrolase in ETrA-fed rats. In EPA-fed rats, there was inhibition of LTB₄ and the all-trans isomers of LTB₄, but there was no inhibition of 5-HETE. This pattern indicates inhibition of LTA synthase in EPA-fed rats. The results establish that dietary ETrA effectively inhibits synthesis of the inflammatory mediator, LTB₄, and suggest that ETrA may confer antiinflammatory benefits similar to those observed with EFAD or dietary fish oil (which contains EPA). Because ETrA is substantially less unsaturated than EPA, it can expected to have greater chemical stability, which could be an important practical advantage when used as a dietary constituent or supplement.