The low level of EPA in brain phospholipids is maintained by multiple compensatory mechanisms

Abstract

ObjectiveTo examine if mitochondrial fatty acid beta‐oxidation is necessary for maintaining low EPA levels in brain phospholipids.MethodsAdult male free‐living Sprague Dawley rats were administered vehicle or methyl palmoxirate (MEP), a carnitine palmitoyltransferase I (CPTI) antagonist prior to being infused intravenously with 150 μCi/kg of 14C‐radiolabeled palmitate, DHA or EPA. Blood samples were collected during the five minute infusion via the jugular vein. At 5 minutes with continual radiotracer infusion, rats were subjected to high‐energy, head‐focused microwave irradiation and brains were collected for radioactive and biochemical analyses.ResultsUsing equations from our fatty acid model, we found that that incorporation coefficient (k*) into the aqueous fraction (marker of β‐oxidation) decreased significantly in MEP‐treated brains compared to vehicle controls for palmitate (3.8‐fold) and EPA (2.2‐fold) but not DHA. This was accompanied by a significant increase in the k* into total phospholipids of MEP‐treated brains as compared to controls for 14C‐EPA infused rats (1.5‐fold) but not 14C‐palmitate and 14C‐DHA infused rats. However, after identification and correction for metabolized 14C‐EPA, the increase in k* was attributed to an increase in synthesis of the EPA elongation product, n‐3 docosapentaenoic acid. Furthermore, the incorporation (Jin) and recycling (FFA) of EPA into brain phospholipids were significantly lower than palmitate and DHA by up to 56‐fold and 9‐fold, respectively.ConclusionThe low level of EPA in brain phospholipids is maintained via beta‐oxidation, elongation and rapid metabolisms.Grant Funding Source: NSERC