Rapid β-oxidation of eicosapentaenoic acid in mouse brain: An in situ study

Chen, Chuck T.; Liu, Zhen; Ouellet, Melissa; Calon, Frédéric; Bazinet, Richard P.

doi:10.1016/j.plefa.2009.01.005

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Volume 80, Issue 2 , Pages 157-163, February 2009

Rapid β-oxidation of eicosapentaenoic acid in mouse brain: An in situ study

Chuck T. Chen
- Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, FitzGerald Building, 150 College St., Room 306, Toronto, Ontario, Canada M5S 3E2
- Corresponding author.
Zhen Liu
- Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, FitzGerald Building, 150 College St., Room 306, Toronto, Ontario, Canada M5S 3E2
Melissa Ouellet
- Faculty of Pharmacy, Laval University and Molecular Endocrinology and Oncology Research Center, Centre Hospitalier de l’Université Laval (CHUL) Research Center, 2705 Boulevard Laurier, Québec, Canada G1V 4G2
Frédéric Calon
- Faculty of Pharmacy, Laval University and Molecular Endocrinology and Oncology Research Center, Centre Hospitalier de l’Université Laval (CHUL) Research Center, 2705 Boulevard Laurier, Québec, Canada G1V 4G2
- These laboratories contributed equally to this work.
- Tel.: +14186542296.
Richard P. Bazinet
- Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, FitzGerald Building, 150 College St., Room 306, Toronto, Ontario, Canada M5S 3E2
- These laboratories contributed equally to this work.
- Tel.: +14169468276; fax: +14169785882.

Received 10 October 2008; received in revised form 5 December 2008; accepted 8 January 2009. published online 25 August 2009.

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 β-oxidized upon its entry into the brain. Wild-type C57BL/6 mice were perfused with either ¹⁴C-EPA or ¹⁴C-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. ¹⁴C-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, μl/g) was calculated. The V_D between ¹⁴C-EPA- and ¹⁴C-DHA-perfused samples was not statistically different for total lipid, neutral lipids or total phospholipids. However, the V_D of ¹⁴C-EPA in the aqueous fraction was 2.5 times higher than that of ¹⁴C-DHA (p=0.025), suggesting a more extensive β-oxidation than DHA. Furthermore, radiolabeled palmitoleic acid, a fatty acid that can be synthesized de novo, was detected in brain phospholipids from ¹⁴C-EPA but not from ¹⁴C-DHA-perfused mice suggesting that β-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 β-oxidation upon uptake by the brain.