Arachidonic acid offsets the effects on mouse brain and behavior of a diet with a low (n-6):(n-3) ratio and very high levels of docosahexaenoic acid.

This study investigated the effects of varying dietary levels of very long-chain polyunsaturated fatty acids on growth, brain fatty acid composition and behavior in mice. Five groups of pregnant and lactating B6D2F1 mice were fed diets with either a very high (n-6):(n-3) ratio of 49 [(n-3) deficient)], a normal ratio of 4.0 or a low ratio of 0.32. The (n-6) fatty acids (FA) were provided either entirely as linoleic acid (LA) or as LA in combination with arachidonic acid (ARA), and the (n-6):(n-3) ratios were adjusted by partial replacement of the (n-6) FA with docosahexaenoic acid (DHA). Offspring were maintained on these diets after weaning. The diets with the low (n-6): (n-3) ratio had no effect on the birth weights of the pups, but after 15 d resulted in a significant 12% reduction in body weights. This effect persisted to adulthood and was apparent in both brain and body weights unless ARA was substituted partially for LA as the source of (n-6) FA. There were significant effects of diet on brain fatty acid composition. Increasing levels of DHA in the diet increased brain DHA and decreased ARA, and there was also retroconversion of DHA in EPA in the mice fed high levels of DHA. Addition of ARA to the diet increased brain ARA, and, at high levels only, decreased DHA. There were no effects of this wide variation in dietary (n-6):(n-3) ratio on the ability of the mice to learn the place of the hidden platform in the Morris water maze. However, in both the cued and the place learning, the mice fed the low (n-6):(n-3) diet swam more slowly, unless ARA substituted partially for LA as the source of (n-6) FA. There were no effects of diet on activity in the spatial open field. These findings show that the effects of a diet with a low (n-6):(n-3) ratio and (n-3) FA provided as DHA, can be overcome if LA is partially replaced by ARA as the source of (n-6) FA.