title: Inhibiting mitochondrial β-oxidation selectively reduces levels of nonenzymatic oxidative polyunsaturated fatty acid metabolites in the brain.
abstract: Schönfeld and Reiser recently hypothesized that fatty acid β-oxidation is a source of oxidative stress in the brain. To test this hypothesis, we inhibited brain mitochondrial β-oxidation with methyl palmoxirate (MEP) and measured oxidative polyunsaturated fatty acid (PUFA) metabolites in the rat brain. Upon MEP treatment, levels of several nonenzymatic auto-oxidative PUFA metabolites were reduced with few effects on enzymatically derived metabolites. Our finding confirms the hypothesis that reduced fatty acid β-oxidation decreases oxidative stress in the brain and β-oxidation inhibitors may be a novel therapeutic approach for brain disorders associated with oxidative stress.
authors: Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors: Chuck T
authors: CT
authors: Chen
authors: Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors: Marc-Olivier
authors: MO
authors: Trépanier
authors: Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors: Kathryn E
authors: KE
authors: Hopperton
authors: Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors: Anthony F
authors: AF
authors: Domenichiello
authors: 1] Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada [2] Nestlé Institute of Health Sciences SA, Lausanne, Switzerland.
authors: Mojgan
authors: M
authors: Masoodi
authors: Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors: Richard P
authors: RP
authors: Bazinet
mesh_terms: D000818:Animals; D001237:Asphyxia / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D004852:Epoxy Compounds / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D008297:Male; D008872:Microwaves; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects / Q000528:radiation effects; D011422:Propionates / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004852:Epoxy Compounds; D005231:Fatty Acids, Unsaturated; D011422:Propionates; C017522:methyl 2-tetradecylglycidate