Nutritional Deprivation of α‐Linolenic Acid Decreases but Does Not Abolish Turnover and Availability of Unacylated Docosahexaenoic Acid and Docosahexaenoyl‐CoA in Rat Brain

Abstract: We applied our in vivo fatty acid method to examine concentrations, incorporation, and turnover rates of docosahexaenoic acid (22:6 n‐3) in brains of rats subject to a dietary deficiency of α‐linolenic acid (18:3 n‐3) for three generations. Adult deficient and adequate rats of the F3 generation were infused intravenously with [4,5‐3H]docosahexaenoic acid over 5 min, after which brain uptake and distribution of tracer were measured. Before infusion, the plasma 22:6 n‐3 level was 0.2 nmol ml‐1 in 18:3 n‐3‐deficient compared with 10.6 nmol ml‐1 in control rats. Brain unesterified 22:6 n‐3 was not detectable, whereas docosahexaenoyl‐CoA content was reduced by 95%, and 22:6 n‐3 content in different phospholipid classes was reduced by 83‐88% in deficient rats. Neither plasma or brain arachidonic acid (20:4 n‐6) level was significantly changed with diet. Docosapentaenoic acid (22:5 n‐6) reciprocally replaced 22:6 n‐3 in brain phospholipids. Calculations using operational equations from our model indicated that 22:6 n‐3 incorporation from plasma into brain was reduced 40‐fold by 18:3 n‐3 deficiency. Recycling of 22:6 n‐3 due to deacylation‐reacylation within phospholipids was reduced by 30‐70% with the deficient diet, but animals nevertheless continued to produce 22:6 n‐3 and docosahexaenoyl‐CoA for brain function. We propose that functional brain effects of n‐3 deficiency reflect altered ratios of n‐6 to n‐3 fatty acids.