title: The low levels of eicosapentaenoic acid in rat brain phospholipids are maintained via multiple redundant mechanisms.
abstract: 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 (14)C-palmitate, (14)C-DHA, or (14)C-EPA. MEP reduced the radioactivity of brain aqueous fractions for (14)C-palmitate-, (14)C-EPA-, and (14)C-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.
authors.affiliation: Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: Chuck T
authors.initials: CT
authors.lastname: Chen
authors.forename: Anthony F
authors.initials: AF
authors.lastname: Domenichiello
authors.forename: Marc-Olivier
authors.initials: MO
authors.lastname: Trépanier
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
authors.forename: Mojgan
authors.initials: M
authors.lastname: Masoodi
authors.forename: Richard P
authors.initials: RP
authors.lastname: Bazinet
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D015118:Eicosapentaenoic Acid / Q000097:blood / Q000378:metabolism*; D004951:Esterification; D007700:Kinetics; D008297:Male; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000097:blood / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014867:Water / Q000737:chemistry
chemical_list: D010743:Phospholipids; D014867:Water; D015118:Eicosapentaenoic Acid
keywords: incorporation; kinetics; turnover; β-oxidation