Dietary n‐6 polyunsaturated fatty acid deprivation increases docosahexaenoic acid metabolism in rat brain

J. Neurochem. (2012) 120 , 985–997. 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.