ROLE OF THE BLOOD-BRAIN-BARRIER IN THE FORMATION OF LONG-CHAIN OMEGA-3 AND OMEGA-6 FATTY-ACIDS FROM ESSENTIAL FATTY-ACID PRECURSORS

Elongated, more highly polyunsaturated derivatives of linoleic acid (18:2ω‐6) and linolenic acid (18:3ω‐3) accumulate in brain, but their sites of synthesis and mechanism of entry are not well characterized. To investigate the role of the blood‐brain barrier in this process, cultured murine cere‐bromicrovascular endothelia were incubated with [1‐14C]18: 2ω‐6 or [1‐14C]18:3ω‐3 and their elongation/desaturation products determined. The major metabolite of 18:2ω‐6 was 20:4ω‐6, whereas the primary product from 18:3ω‐3 was 20: 5ω‐3. Although these products were found primarily in cell lipids, they were also released from the cells and gradually accumulated in the extracellular fluid. Eicosanoid production was observed from the 20:4ω‐6 and 20:5ω‐3 that were formed. No 22:5ω‐6 or 22:6ω‐3 fatty acids were detected, suggesting that these endothelial cells are not the site of the final desaturation step. Although the uptake of 18:3ω‐3 and 18:2ω‐6 was nearly identical, 18:3ω‐3 was more extensively elongated and desaturated. Competition experiments demonstrated a preference for 18:3ω‐3 by the elongation/desaturation pathway. These findings suggest that the blood‐brain barrier can play an important role in the elongation and desaturation of ω‐3 and ω‐6 essential fatty acids during their transfer from the circulation into the brain. Copyright © 1990, Wiley Blackwell. All rights reserved