The low levels of eicosapentaenoic acid in rat brain phospholipids are maintained via multiple redundant mechanisms

Brain eicosapentaenoic acid (EPA) levels are 250- to 300-fold lower than docosahexaenoic acid (DHA), at least partly, because EPA is rapidly β-oxidized and lost from brain phospholipids. Therefore, we examined if β-oxidation was necessary for maintaining low EPA levels by inhibiting β-oxidation with...

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Main Authors: Chuck T. Chen, Anthony F. Domenichiello, Marc-Olivier Trépanier, Zhen Liu, Mojgan Masoodi, Richard P. Bazinet
Format: Article
Language:English
Published: Elsevier 2013-09-01
Series:Journal of Lipid Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0022227520351312
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author Chuck T. Chen
Anthony F. Domenichiello
Marc-Olivier Trépanier
Zhen Liu
Mojgan Masoodi
Richard P. Bazinet
author_facet Chuck T. Chen
Anthony F. Domenichiello
Marc-Olivier Trépanier
Zhen Liu
Mojgan Masoodi
Richard P. Bazinet
author_sort Chuck T. Chen
collection DOAJ
description Brain eicosapentaenoic acid (EPA) levels are 250- to 300-fold lower than docosahexaenoic acid (DHA), at least partly, because EPA is rapidly β-oxidized and lost from brain phospholipids. Therefore, we examined if β-oxidation was necessary for maintaining low EPA levels by inhibiting β-oxidation with methyl palmoxirate (MEP). Furthermore, because other metabolic differences between DHA and EPA may also contribute to their vastly different levels, this study aimed to quantify the incorporation and turnover of DHA and EPA into brain phospholipids. Fifteen-week-old rats were subjected to vehicle or MEP prior to a 5 min intravenous infusion of 14C-palmitate, 14C-DHA, or 14C-EPA. MEP reduced the radioactivity of brain aqueous fractions for 14C-palmitate-, 14C-EPA-, and 14C-DHA-infused rats by 74, 54, and 23%, respectively; while it increased the net rate of incorporation of plasma unesterified palmitate into choline glycerophospholipids and phosphatidylinositol and EPA into ethanolamine glycerophospholipids and phosphatidylserine. MEP also increased the synthesis of n-3 docosapentaenoic acid (n-3 DPA) from EPA. Moreover, the recycling of EPA into brain phospholipids was 154-fold lower than DHA. Therefore, the low levels of EPA in the brain are maintained by multiple redundant pathways including β-oxidation, decreased incorporation from plasma unesterified FA pool, elongation/desaturation to n-3 DPA, and lower recycling within brain phospholipids.
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spelling doaj.art-478684076c734aa9a0a6ef70e6bb0cbb2022-12-21T18:53:41ZengElsevierJournal of Lipid Research0022-22752013-09-0154924102422The low levels of eicosapentaenoic acid in rat brain phospholipids are maintained via multiple redundant mechanismsChuck T. Chen0Anthony F. Domenichiello1Marc-Olivier Trépanier2Zhen Liu3Mojgan Masoodi4Richard P. Bazinet5Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada M5S 3E2; andDepartment of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada M5S 3E2; andDepartment of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada M5S 3E2; andDepartment of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada M5S 3E2; andNestlé Institute of Health Sciences SA, Campus EPFL, Quartier de l'innovation, bâtiment G, 1015 Lausanne, SwitzerlandTo whom correspondence should be addressed; Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada M5S 3E2; andBrain eicosapentaenoic acid (EPA) levels are 250- to 300-fold lower than docosahexaenoic acid (DHA), at least partly, because EPA is rapidly β-oxidized and lost from brain phospholipids. Therefore, we examined if β-oxidation was necessary for maintaining low EPA levels by inhibiting β-oxidation with methyl palmoxirate (MEP). Furthermore, because other metabolic differences between DHA and EPA may also contribute to their vastly different levels, this study aimed to quantify the incorporation and turnover of DHA and EPA into brain phospholipids. Fifteen-week-old rats were subjected to vehicle or MEP prior to a 5 min intravenous infusion of 14C-palmitate, 14C-DHA, or 14C-EPA. MEP reduced the radioactivity of brain aqueous fractions for 14C-palmitate-, 14C-EPA-, and 14C-DHA-infused rats by 74, 54, and 23%, respectively; while it increased the net rate of incorporation of plasma unesterified palmitate into choline glycerophospholipids and phosphatidylinositol and EPA into ethanolamine glycerophospholipids and phosphatidylserine. MEP also increased the synthesis of n-3 docosapentaenoic acid (n-3 DPA) from EPA. Moreover, the recycling of EPA into brain phospholipids was 154-fold lower than DHA. Therefore, the low levels of EPA in the brain are maintained by multiple redundant pathways including β-oxidation, decreased incorporation from plasma unesterified FA pool, elongation/desaturation to n-3 DPA, and lower recycling within brain phospholipids.http://www.sciencedirect.com/science/article/pii/S0022227520351312incorporationturnoverkineticsβ-oxidation
spellingShingle Chuck T. Chen
Anthony F. Domenichiello
Marc-Olivier Trépanier
Zhen Liu
Mojgan Masoodi
Richard P. Bazinet
The low levels of eicosapentaenoic acid in rat brain phospholipids are maintained via multiple redundant mechanisms
Journal of Lipid Research
incorporation
turnover
kinetics
β-oxidation
title The low levels of eicosapentaenoic acid in rat brain phospholipids are maintained via multiple redundant mechanisms
title_full The low levels of eicosapentaenoic acid in rat brain phospholipids are maintained via multiple redundant mechanisms
title_fullStr The low levels of eicosapentaenoic acid in rat brain phospholipids are maintained via multiple redundant mechanisms
title_full_unstemmed The low levels of eicosapentaenoic acid in rat brain phospholipids are maintained via multiple redundant mechanisms
title_short The low levels of eicosapentaenoic acid in rat brain phospholipids are maintained via multiple redundant mechanisms
title_sort low levels of eicosapentaenoic acid in rat brain phospholipids are maintained via multiple redundant mechanisms
topic incorporation
turnover
kinetics
β-oxidation
url http://www.sciencedirect.com/science/article/pii/S0022227520351312
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