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Dietary docosahexaenoic acid supplementation enhances expression of fatty acid‐binding protein 5 at the blood–brain barrier and brain docosahexaenoic acid levels
Author(s) -
Pan Yijun,
Morris Elonie R.,
Scanlon Martin J.,
Marriott Philip J.,
Porter Christopher J. H.,
Nicolazzo Joseph A.
Publication year - 2018
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.14342
Subject(s) - docosahexaenoic acid , blood–brain barrier , fatty acid binding protein , fatty acid , endocrinology , biochemistry , polyunsaturated fatty acid , biology , medicine , chemistry , central nervous system , gene
The cytoplasmic trafficking of docosahexaenoic acid ( DHA ), a cognitively beneficial fatty acid, across the blood–brain barrier ( BBB ) is governed by fatty acid‐binding protein 5 ( FABP 5). Lower levels of brain DHA have been observed in Alzheimer's disease ( AD ), which is associated with diminished BBB expression of FABP 5. Therefore, up‐regulating FABP 5 expression at the BBB may be a novel approach for enhancing BBB transport of DHA in AD . DHA supplementation has been shown to be beneficial in various mouse models of AD , and therefore, the aim of this study was to determine whether DHA has the potential to up‐regulate the BBB expression of FABP 5, thereby enhancing its own uptake into the brain. Treating human brain microvascular brain endothelial ( hCMEC /D3) cells with the maximum tolerable concentration of DHA (12.5 μM) for 72 h resulted in a 1.4‐fold increase in FABP 5 protein expression. Associated with this was increased expression of fatty acid transport proteins 1 and 4. To study the impact of dietary DHA supplementation, 6‐ to 8‐week‐old C57 BL /6 mice were fed with a control diet or a DHA ‐enriched diet for 21 days. Brain microvascular FABP 5 protein expression was up‐regulated 1.7‐fold in mice fed the DHA ‐enriched diet, and this was associated with increased brain DHA levels (1.3‐fold). Despite an increase in brain DHA levels, reduced BBB transport of 14 C‐ DHA was observed over a 1 min perfusion, possibly as a result of competitive binding to FABP 5 between dietary DHA and 14 C‐ DHA . This study has demonstrated that DHA can increase BBB expression of FABP 5, as well as fatty acid transporters, overall increasing brain DHA levels.