Plasma non-esterified docosahexaenoic acid is the major pool supplying the brain: Plasma NEFA pool supplies the brain with DHA

Chuck T. Chen; Alex P. Kitson; Kathryn E. Hopperton; Antony F Domenichiello; Mark O. Trepanier; Lauren E. Lin; Leonardo Ermini; Martin Post; Frank Thies; Richard P.  Bazinet

doi:10.1038/srep15791

Plasma non-esterified docosahexaenoic acid is the major pool supplying the brain: Plasma NEFA pool supplies the brain with DHA

Chuck T. Chen, Alex P. Kitson, Kathryn E. Hopperton, Antony F Domenichiello, Mark O. Trepanier, Lauren E. Lin, Leonardo Ermini, Martin Post, Frank Thies, Richard P. Bazinet (Corresponding Author)

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Abstract

Despite being critical for normal brain function, the pools that supply docosahexaenoic acid (DHA) to the brain are not agreed upon. Using multiple kinetic models in free-living adult rats, we first demonstrate that DHA uptake from the plasma non-esterified fatty acid (NEFA) pool predicts brain uptake of DHA upon oral administration, which enters the plasma NEFA pool as
well as multiple plasma esterified pools. The rate of DHA loss by the brain is similar to the uptake from the plasma NEFA pool. Furthermore, upon acute iv administration, although more radiolabeled lysophosphatidylcholine (LPC)-DHA enters the brain than NEFA-DHA, this is due to the longer plasma half-life and exposure to the brain. Direct comparison of the uptake rate of LPC-DHA and NEFA-DHA demonstrates that uptake of NEFA-DHA into the brain is 10-fold greater than LPC-DHA. In conclusion, plasma NEFA-DHA is the major plasma pool supplying the brain.

Original language	English
Article number	15791
Number of pages	12
Journal	Scientific Reports
Volume	5
DOIs	https://doi.org/10.1038/srep15791
Publication status	Published - 29 Oct 2015

Bibliographical note

Acknowledgements This project was funded by a NSERC and CIHR grant to R.P.B. and studentship to C.T.C. R.P.B. holds a Canada Research Chair in Brain Lipid Metabolism. R.P.B. acknowledges support and mass spectrometry equipment and solutions for lipidomics from Sciex. Computer programmable pump software was designed by Dr. Brian Scott. HPLC analyses were performed at the Analytical Facility at the Department of Nutritional Sciences by Dr. Zhen Liu. LC/MS/MS analyses of NEFA-DHA and LPC-DHA and MALDI imaging were performed at the Analytical Facility for Bioactive Molecules (AFBM) with the assistance of Michael Leadley. The AFBM is part of the Centre for the Study of Complex Childhood Diseases (CSCCD) at the Hospital for Sick Children, Toronto, Ontario. CSCCD was supported by Canadian Foundation for Innovation (CFI).

Keywords

DHA
LPC-DHA
brain uptake

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Plasma non-esterified docosahexaenoic acid is the major pool supplying the brain
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Frank Thies
- School of Medicine, Medical Sciences & Nutrition, Aberdeen Cardiovascular and Diabetes Centre
- School of Medicine, Medical Sciences & Nutrition, The Rowett Institute of Nutrition and Health - Reader
Person: Academic

Cite this

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title = "Plasma non-esterified docosahexaenoic acid is the major pool supplying the brain: Plasma NEFA pool supplies the brain with DHA",

abstract = "Despite being critical for normal brain function, the pools that supply docosahexaenoic acid (DHA) to the brain are not agreed upon. Using multiple kinetic models in free-living adult rats, we first demonstrate that DHA uptake from the plasma non-esterified fatty acid (NEFA) pool predicts brain uptake of DHA upon oral administration, which enters the plasma NEFA pool aswell as multiple plasma esterified pools. The rate of DHA loss by the brain is similar to the uptake from the plasma NEFA pool. Furthermore, upon acute iv administration, although more radiolabeled lysophosphatidylcholine (LPC)-DHA enters the brain than NEFA-DHA, this is due to the longer plasma half-life and exposure to the brain. Direct comparison of the uptake rate of LPC-DHA and NEFA-DHA demonstrates that uptake of NEFA-DHA into the brain is 10-fold greater than LPC-DHA. In conclusion, plasma NEFA-DHA is the major plasma pool supplying the brain.",

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author = "Chen, {Chuck T.} and Kitson, {Alex P.} and Hopperton, {Kathryn E.} and Domenichiello, {Antony F} and Trepanier, {Mark O.} and Lin, {Lauren E.} and Leonardo Ermini and Martin Post and Frank Thies and Bazinet, {Richard P.}",

note = "Acknowledgements This project was funded by a NSERC and CIHR grant to R.P.B. and studentship to C.T.C. R.P.B. holds a Canada Research Chair in Brain Lipid Metabolism. R.P.B. acknowledges support and mass spectrometry equipment and solutions for lipidomics from Sciex. Computer programmable pump software was designed by Dr. Brian Scott. HPLC analyses were performed at the Analytical Facility at the Department of Nutritional Sciences by Dr. Zhen Liu. LC/MS/MS analyses of NEFA-DHA and LPC-DHA and MALDI imaging were performed at the Analytical Facility for Bioactive Molecules (AFBM) with the assistance of Michael Leadley. The AFBM is part of the Centre for the Study of Complex Childhood Diseases (CSCCD) at the Hospital for Sick Children, Toronto, Ontario. CSCCD was supported by Canadian Foundation for Innovation (CFI).",

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AU - Hopperton, Kathryn E.

AU - Domenichiello, Antony F

AU - Trepanier, Mark O.

AU - Lin, Lauren E.

AU - Ermini, Leonardo

AU - Post, Martin

AU - Thies, Frank

AU - Bazinet, Richard P.

N1 - Acknowledgements This project was funded by a NSERC and CIHR grant to R.P.B. and studentship to C.T.C. R.P.B. holds a Canada Research Chair in Brain Lipid Metabolism. R.P.B. acknowledges support and mass spectrometry equipment and solutions for lipidomics from Sciex. Computer programmable pump software was designed by Dr. Brian Scott. HPLC analyses were performed at the Analytical Facility at the Department of Nutritional Sciences by Dr. Zhen Liu. LC/MS/MS analyses of NEFA-DHA and LPC-DHA and MALDI imaging were performed at the Analytical Facility for Bioactive Molecules (AFBM) with the assistance of Michael Leadley. The AFBM is part of the Centre for the Study of Complex Childhood Diseases (CSCCD) at the Hospital for Sick Children, Toronto, Ontario. CSCCD was supported by Canadian Foundation for Innovation (CFI).

PY - 2015/10/29

Y1 - 2015/10/29

N2 - Despite being critical for normal brain function, the pools that supply docosahexaenoic acid (DHA) to the brain are not agreed upon. Using multiple kinetic models in free-living adult rats, we first demonstrate that DHA uptake from the plasma non-esterified fatty acid (NEFA) pool predicts brain uptake of DHA upon oral administration, which enters the plasma NEFA pool aswell as multiple plasma esterified pools. The rate of DHA loss by the brain is similar to the uptake from the plasma NEFA pool. Furthermore, upon acute iv administration, although more radiolabeled lysophosphatidylcholine (LPC)-DHA enters the brain than NEFA-DHA, this is due to the longer plasma half-life and exposure to the brain. Direct comparison of the uptake rate of LPC-DHA and NEFA-DHA demonstrates that uptake of NEFA-DHA into the brain is 10-fold greater than LPC-DHA. In conclusion, plasma NEFA-DHA is the major plasma pool supplying the brain.

AB - Despite being critical for normal brain function, the pools that supply docosahexaenoic acid (DHA) to the brain are not agreed upon. Using multiple kinetic models in free-living adult rats, we first demonstrate that DHA uptake from the plasma non-esterified fatty acid (NEFA) pool predicts brain uptake of DHA upon oral administration, which enters the plasma NEFA pool aswell as multiple plasma esterified pools. The rate of DHA loss by the brain is similar to the uptake from the plasma NEFA pool. Furthermore, upon acute iv administration, although more radiolabeled lysophosphatidylcholine (LPC)-DHA enters the brain than NEFA-DHA, this is due to the longer plasma half-life and exposure to the brain. Direct comparison of the uptake rate of LPC-DHA and NEFA-DHA demonstrates that uptake of NEFA-DHA into the brain is 10-fold greater than LPC-DHA. In conclusion, plasma NEFA-DHA is the major plasma pool supplying the brain.

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KW - LPC-DHA

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M1 - 15791

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Plasma non-esterified docosahexaenoic acid is the major pool supplying the brain: Plasma NEFA pool supplies the brain with DHA

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