The antithetic relationship of dietary arachidonic acid and eicosapentaenoic acid : a comparison of indices of lipid metabolism and eicosanoid production

Low to moderate levels of dietary arachidonic acid (20:4 n-6, AA) significantly enriches AA in tissue phospholipids and augment the in vitro production of its oxidized derivatives, eicosanoids. The effects of eicosapentaenoic acid (20:5 n-3, EPA) appear to be diametrically opposite to those of AA. This study is designed to evaluate this antithetic relationship of dietary AA and EPA. Forty-nine CD-1 mice were randomly assigned to four dietary groups: oleic acid (18:1 n-9, OA) group as control, AA group, EPA group, and AA+EPA group. Each diet contained identical amounts of saturated fat, monounsaturated fat, and polyunsaturated fat. Additionally, each diet was supplemented with combinations of OA, AA and EPA ethyl esters (3%, w/w). Animals were on diets for 4 weeks. Prior to sacrifice, production and release of eicosanoids were induced by stimulating residence peritoneal macrophages with opsonized zymosan. Fatty acid composition was analyzed in perfused liver. AA feeding significantly enriched AA concentration in hepatic phospholipids. Dietary EPA enriched hepatic phospholipids with EPA at the expense of AA. Adding AA to the EPA containing diet replenished tissue AA content to the control levels, while tissue EPA levels declined from 6.5 mole% in the EPA group to 0.4 mole % in the AA+EPA group. Similar effects were also observed with eicosanoid production. AA feeding significantly enhanced the formation of eicosanoids while dietary EPA depressed them. AA+EPA feeding elevated eicosanoid formation by 46% and 390% compared to the OA control group (p<0.05) and the EPA group (p<0.05), respectively. These changes of eicosanoid formation appeared to be regulated in part by phospholipid AA content, as phospholipid AA content was significantly (p<0.01) and positively correlated with the formation of AA-derived eicosanoids. In summary, while dietary EPA potently depresses phospholipid AA content and AA-derived eicosanoid formation, dietary AA diminishes these effects of EPA and appears to be a more potent modulator for fatty acid composition and eicosanoid formation.