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The blood‐brain barrier fatty acid transport protein 1 ( FATP 1/ SLC 27A1) supplies docosahexaenoic acid to the brain, and insulin facilitates transport
Author(s) -
Ochiai Yusuke,
Uchida Yasuo,
Ohtsuki Sumio,
Tachikawa Masanori,
Aizawa Sanshiro,
Terasaki Tetsuya
Publication year - 2017
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.13943
Subject(s) - docosahexaenoic acid , biology , blood–brain barrier , biochemistry , fatty acid , efflux , oleic acid , microbiology and biotechnology , endocrinology , polyunsaturated fatty acid , central nervous system
We purposed to clarify the contribution of fatty acid transport protein 1 ( FATP 1/SLC 27A1) to the supply of docosahexaenoic acid ( DHA ) to the brain across the blood–brain barrier in this study. Transport experiments showed that the uptake rate of [ 14 C]‐ DHA in human FATP 1‐expressing HEK 293 cells was significantly greater than that in empty vector‐transfected (mock) HEK 293 cells. The steady‐state intracellular DHA concentration was nearly 2‐fold smaller in FATP 1‐expressing than in mock cells, suggesting that FATP 1 works as not only an influx, but also an efflux transporter for DHA . [ 14 C]‐ DHA uptake by a human cerebral microvascular endothelial cell line ( hCMEC /D3) increased in a time‐dependent manner, and was inhibited by unlabeled DHA and a known FATP 1 substrate, oleic acid. Knock‐down of FATP 1 in hCMEC /D3 cells with specific si RNA showed that FATP 1‐mediated uptake accounts for 59.2–73.0% of total [ 14 C]‐ DHA uptake by the cells. Insulin treatment for 30 min induced translocation of FATP 1 protein to the plasma membrane in hCMEC /D3 cells and enhanced [ 14 C]‐ DHA uptake. Immunohistochemical analysis of mouse brain sections showed that FATP 1 protein is preferentially localized at the basal membrane of brain microvessel endothelial cells. We found that two neuroprotective substances, taurine and biotin, in addition to DHA , undergo FATP 1‐mediated efflux. Overall, our results suggest that FATP 1 localized at the basal membrane of brain microvessels contributes to the transport of DHA , taurine and biotin into the brain, and insulin rapidly increases DHA supply to the brain by promoting translocation of FATP 1 to the membrane.Read the Editorial Comment for this article on page 324.