title: Rapid beta-oxidation of eicosapentaenoic acid in mouse brain: an in situ study.
abstract: Analyses of brain phospholipid fatty acid profiles reveal a selective deficiency and enrichment in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), respectively. In order to account for this difference in brain fatty acid levels, we hypothesized that EPA is more rapidly beta-oxidized upon its entry into the brain. Wild-type C57BL/6 mice were perfused with either (14)C-EPA or (14)C-DHA via in situ cerebral perfusion for 40s, followed by a bicarbonate buffer to wash out the residual radiolabeled polyunsaturated fatty acid (PUFA) in the capillaries. (14)C-PUFA-perfused brains were extracted for chemical analyses of neutral lipid and phospholipid fatty acids. Based on the radioactivity in aqueous, total lipid, neutral lipid and phospholipid fractions, volume of distribution (V(D), microl/g) was calculated. The V(D) between (14)C-EPA- and (14)C-DHA-perfused samples was not statistically different for total lipid, neutral lipids or total phospholipids. However, the V(D) of (14)C-EPA in the aqueous fraction was 2.5 times higher than that of (14)C-DHA (p=0.025), suggesting a more extensive beta-oxidation than DHA. Furthermore, radiolabeled palmitoleic acid, a fatty acid that can be synthesized de novo, was detected in brain phospholipids from (14)C-EPA but not from (14)C-DHA-perfused mice suggesting that beta-oxidation products of EPA were recycled into endogenous fatty acid biosynthetic pathways. These findings suggest that low levels of EPA in brain phospholipids compared to DHA may be the result of its rapid beta-oxidation upon uptake by the brain.
authors.affiliation: Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, FitzGerald Building, 150 College St., Room 306, Toronto, Ontario, Canada M5S 3E2. tzu.huan.chuck.chen@gmail.com
authors.forename: Chuck T
authors.initials: CT
authors.lastname: Chen
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
authors.forename: Melissa
authors.initials: M
authors.lastname: Ouellet
authors.forename: Frédéric
authors.initials: F
authors.lastname: Calon
authors.forename: Richard P
authors.initials: RP
authors.lastname: Bazinet
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D002788:Cholesterol Esters / Q000737:chemistry / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004281:Docosahexaenoic Acids / Q000032:analysis / Q000378:metabolism; D015118:Eicosapentaenoic Acid / Q000032:analysis / Q000378:metabolism*; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction; D010477:Perfusion; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism; D014280:Triglycerides / Q000737:chemistry / Q000378:metabolism
chemical_list: D002788:Cholesterol Esters; D008055:Lipids; D010743:Phospholipids; D014280:Triglycerides; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid