Rapid β-oxidation of eicosapentaenoic acid in mouse brain: An in situ study

Analyses of brain phospholipid fatty acid profiles reveal a selective deficiency and enrichment in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), respectively. In order to account for this difference in brain fatty acid levels, we hypothesized that EPA is more rapidly β-oxidized upon its entry into the brain. Wild-type C57BL/6 mice were perfused with either 14C-EPA or 14C-DHA via in situ cerebral perfusion for 40s, followed by a bicarbonate buffer to wash out the residual radiolabeled polyunsaturated fatty acid (PUFA) in the capillaries. 14C-PUFA-perfused brains were extracted for chemical analyses of neutral lipid and phospholipid fatty acids. Based on the radioactivity in aqueous, total lipid, neutral lipid and phospholipid fractions, volume of distribution (VD, μl/g) was calculated. The VD between 14C-EPA- and 14C-DHA-perfused samples was not statistically different for total lipid, neutral lipids or total phospholipids. However, the VD of 14C-EPA in the aqueous fraction was 2.5 times higher than that of 14C-DHA (p=0.025), suggesting a more extensive β-oxidation than DHA. Furthermore, radiolabeled palmitoleic acid, a fatty acid that can be synthesized de novo, was detected in brain phospholipids from 14C-EPA but not from 14C-DHA-perfused mice suggesting that β-oxidation products of EPA were recycled into endogenous fatty acid biosynthetic pathways. These findings suggest that low levels of EPA in brain phospholipids compared to DHA may be the result of its rapid β-oxidation upon uptake by the brain.