Dietary docosahexaenoic acid supplementation enhances expression of fatty acid-binding protein 5 at the blood–brain barrier and brain docosahexaenoic acid levels

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Abstract

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 (FABP5). Lower levels of brain DHA have been observed in Alzheimer's disease (AD), which is associated with diminished BBB expression of FABP5. Therefore, up-regulating FABP5 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 FABP5, 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 FABP5 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 C57BL/6 mice were fed with a control diet or a DHA-enriched diet for 21 days. Brain microvascular FABP5 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 14C-DHA was observed over a 1 min perfusion, possibly as a result of competitive binding to FABP5 between dietary DHA and 14C-DHA. This study has demonstrated that DHA can increase BBB expression of FABP5, as well as fatty acid transporters, overall increasing brain DHA levels. (Figure presented.).

Original languageEnglish
Pages (from-to)186-197
Number of pages12
JournalJournal of Neurochemistry
Volume146
Issue number2
DOIs
Publication statusPublished - 1 Jul 2018

Keywords

  • Alzheimer's disease
  • blood–brain barrier
  • docosahexaenoic acid
  • fatty acid-binding protein 5

Cite this

@article{bdbe3283943043b2a8a5d95a3fffd8bb,
title = "Dietary docosahexaenoic acid supplementation enhances expression of fatty acid-binding protein 5 at the blood–brain barrier and brain docosahexaenoic acid levels",
abstract = "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 (FABP5). Lower levels of brain DHA have been observed in Alzheimer's disease (AD), which is associated with diminished BBB expression of FABP5. Therefore, up-regulating FABP5 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 FABP5, 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 FABP5 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 C57BL/6 mice were fed with a control diet or a DHA-enriched diet for 21 days. Brain microvascular FABP5 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 14C-DHA was observed over a 1 min perfusion, possibly as a result of competitive binding to FABP5 between dietary DHA and 14C-DHA. This study has demonstrated that DHA can increase BBB expression of FABP5, as well as fatty acid transporters, overall increasing brain DHA levels. (Figure presented.).",
keywords = "Alzheimer's disease, blood–brain barrier, docosahexaenoic acid, fatty acid-binding protein 5",
author = "Yijun Pan and Morris, {Elonie R} and Scanlon, {Martin J} and Marriott, {Philip J} and Porter, {Christopher J H} and Nicolazzo, {Joseph A}",
year = "2018",
month = "7",
day = "1",
doi = "10.1111/jnc.14342",
language = "English",
volume = "146",
pages = "186--197",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
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TY - JOUR

T1 - Dietary docosahexaenoic acid supplementation enhances expression of fatty acid-binding protein 5 at the blood–brain barrier and brain docosahexaenoic acid levels

AU - Pan, Yijun

AU - Morris, Elonie R

AU - Scanlon, Martin J

AU - Marriott, Philip J

AU - Porter, Christopher J H

AU - Nicolazzo, Joseph A

PY - 2018/7/1

Y1 - 2018/7/1

N2 - 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 (FABP5). Lower levels of brain DHA have been observed in Alzheimer's disease (AD), which is associated with diminished BBB expression of FABP5. Therefore, up-regulating FABP5 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 FABP5, 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 FABP5 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 C57BL/6 mice were fed with a control diet or a DHA-enriched diet for 21 days. Brain microvascular FABP5 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 14C-DHA was observed over a 1 min perfusion, possibly as a result of competitive binding to FABP5 between dietary DHA and 14C-DHA. This study has demonstrated that DHA can increase BBB expression of FABP5, as well as fatty acid transporters, overall increasing brain DHA levels. (Figure presented.).

AB - 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 (FABP5). Lower levels of brain DHA have been observed in Alzheimer's disease (AD), which is associated with diminished BBB expression of FABP5. Therefore, up-regulating FABP5 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 FABP5, 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 FABP5 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 C57BL/6 mice were fed with a control diet or a DHA-enriched diet for 21 days. Brain microvascular FABP5 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 14C-DHA was observed over a 1 min perfusion, possibly as a result of competitive binding to FABP5 between dietary DHA and 14C-DHA. This study has demonstrated that DHA can increase BBB expression of FABP5, as well as fatty acid transporters, overall increasing brain DHA levels. (Figure presented.).

KW - Alzheimer's disease

KW - blood–brain barrier

KW - docosahexaenoic acid

KW - fatty acid-binding protein 5

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U2 - 10.1111/jnc.14342

DO - 10.1111/jnc.14342

M3 - Article

VL - 146

SP - 186

EP - 197

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

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ER -