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 (18:2 omega-6) and linolenic acid (18:3 omega-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 cerebromicrovascular endothelia were incubated with [1-14C]18:2 omega-6 or [1-14C]18:3 omega-3 and their elongation/desaturation products determined. The major metabolite of 18:2 omega-6 was 20:4 omega-6, whereas the primary product from 18:3 omega-3 was 20:5 omega-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 20:4 omega-6 and 20:5 omega-3 that were formed. No 22:5 omega-6 or 22:6 omega-3 fatty acids were detected, suggesting that these endothelial cells are not the site of the final desaturation step. Although the uptake of 18:3 omega-3 and 18:2 omega-6 was nearly identical, 18:3 omega-3 was more extensively elongated and desaturated. Competition experiments demonstrated a preference for 18:3 omega-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 omega-3 and omega-6 essential fatty acids during their transfer from the circulation into the brain.
Moore
S A
SA
Department of Pathology, University of Iowa, Iowa City 52242.
Yoder
E
E
Spector
A A
AA
D000123:Acetyltransferases / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D001769:Blood; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000098:blood supply; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D015777:Eicosanoids / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000378:metabolism*; D044943:Fatty Acid Desaturases / Q000378:metabolism; D000081031:Fatty Acid Elongases; D005228:Fatty Acids, Essential / Q000378:metabolism*; D015525:Fatty Acids, Omega-3 / Q000096:biosynthesis*; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis*; D008401:Gas Chromatography-Mass Spectrometry; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000378:metabolism; D008042:Linolenic Acids / Q000378:metabolism; D051379:Mice; D008833:Microcirculation / Q000378:metabolism; D051381:Rats
D015777:Eicosanoids; D005228:Fatty Acids, Essential; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated; D008041:Linoleic Acids; D008042:Linolenic Acids; D019787:Linoleic Acid; D044943:Fatty Acid Desaturases; D000123:Acetyltransferases; D000081031:Fatty Acid Elongases