Rapid de-esterification and loss of eicosapentaenoic acid from rat brain phospholipids: an intracerebroventricular study

Abstract

Eicosapentaenoic acid (EPA, 20:5n-3) is being explored as a therapy in neurological diseases and disorders. Although it is known that palmitate is the most abundant fatty acid in the brain while EPA is one of the lowest, the mechanism by which the brain maintains this balance is unclear. Therefore, to trace the metabolism of these fatty acids in the brain, (14) C-palmitate or (14) C-EPA was administered via intracerebroventricular infusion to rats. From 4 to 128 days post-infusion, brains were collected after head-focused, high-energy microwave irradiation for biochemical analysis. At day 4 post-infusion, 57% (82 ± 26 nCi) of the total phospholipid radioactivity in (14) C-palmitate-infused brains was intact palmitate; whereas in (14) C-EPA-infused brains, 9% (2 ± 0.9 nCi) of the radioactivity was intact EPA. The half-life of esterified (14) C-palmitate and (14) C-EPA was 32 ± 4 (2% loss per day) and 5 ± 0.2 days (14% loss per day), respectively. Radioactivity was also detected in other saturates, monounsaturates, and cholesterol, suggesting that the infused radiolabeled fatty acids were β-oxidized. In conclusion, the low concentration of EPA in brain phospholipids may be the result of extensive metabolism of EPA, in part by β-oxidation, upon entry into the brain and upon de-esterification from phospholipids.