title: Dietary n-6 polyunsaturated fatty acid deprivation increases docosahexaenoic acid metabolism in rat brain.
abstract: Dietary n-6 polyunsaturated fatty acid (PUFA) deprivation in rodents reduces brain arachidonic acid (20:4n-6) concentration and 20:4n-6-preferring cytosolic phospholipase A(2) (cPLA(2) -IVA) and cyclooxygenase (COX)-2 expression, while increasing brain docosahexaenoic acid (DHA, 22:6n-3) concentration and DHA-selective calcium-independent phospholipase A(2) (iPLA(2) )-VIA expression. We hypothesized that these changes are accompanied by up-regulated brain DHA metabolic rates. Using a fatty acid model, brain DHA concentrations and kinetics were measured in unanesthetized male rats fed, for 15 weeks post-weaning, an n-6 PUFA 'adequate' (31.4 wt% linoleic acid) or 'deficient' (2.7 wt% linoleic acid) diet, each lacking 20:4n-6 and DHA. [1-(14) C]DHA was infused intravenously, arterial blood was sampled, and the brain was microwaved at 5 min and analyzed. Rats fed the n-6 PUFA deficient compared with adequate diet had significantly reduced n-6 PUFA concentrations in brain phospholipids but increased eicosapentaenoic acid (EPA, 20:5n-3), docosapentaenoic acid n-3 (DPAn-3, 22:5n-3), and DHA (by 9.4%) concentrations, particularly in ethanolamine glycerophospholipid (EtnGpl). Incorporation rates of unesterified DHA from plasma, which represent DHA metabolic loss from brain, were increased 45% in brain phospholipids, as was DHA turnover. Increased DHA metabolism following dietary n-6 PUFA deprivation may increase brain concentrations of antiinflammatory DHA metabolites, which with a reduced brain n-6 PUFA content, likely promotes neuroprotection and alters neurotransmission.
authors: Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA. miki.i@uci.edu
authors: Miki
authors: M
authors: Igarashi
authors: Hyung-Wook
authors: HW
authors: Kim
authors: Lisa
authors: L
authors: Chang
authors: Kaizong
authors: K
authors: Ma
authors: Stanley I
authors: SI
authors: Rapoport
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight; D001921:Brain / Q000378:metabolism*; D002247:Carbon Isotopes / Q000493:pharmacokinetics; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004041:Dietary Fats / Q000008:administration & dosage* / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000378:metabolism* / Q000493:pharmacokinetics; D043371:Fatty Acids, Omega-6 / Q000172:deficiency*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D008055:Lipids / Q000097:blood; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D000214:Acyl Coenzyme A; D002247:Carbon Isotopes; D004041:Dietary Fats; D043371:Fatty Acids, Omega-6; D008055:Lipids; D004281:Docosahexaenoic Acids