Abstract: Oxylipins are bioactive lipids that are formed by monooxygenation of PUFA by cyclooxygenase, lipoxygenase and cytochrome P450 enzymes. Since diet and sex can alter brain fatty acid compositions, it is likely that brain oxylipins also are influenced by differing dietary fatty acids and by sex. However, oxylipins do not always directly reflect PUFA compositions. We therefore examined the brain oxylipin profile by HPLC/MS/MS in weanling male and female rats provided diets that differed in their oil types for 6 weeks. These standard rodent diets differed only in their content of ALA, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and linoleic acid. GC analysis revealed that there was ~1.5 times as much DHA compared to arachidonic acid (ARA) in the brain. In comparison, when examining oxylipins produced by the same enzymes, this was reversed, with higher levels of ARA compared to DHA oxylipins. Effects of dietary PUFA and of sex on brain oxylipins also differed in several aspects when compared to other tissues. For example, the brain oxylipin profile was much more resistant to changes in response to diet when compared to all other tissues examined - liver, kidney, spleen, adipose, muscle and heart. Further, oxylipins that displayed a sex effect were predominantly higher in male brains, similar to the liver, spleen and kidney, but opposite what was observed in the heart, muscle and adipose. In a second experiment, increasing levels of dietary ALA were provided to mice to determine its effects on an oxylipin biomarker of dietary ALA adequacy. This biomarker comprised of DHA and ARA oxylipins demonstrated that the brain’s requirement for dietary ALA is much lower than for several other tissues. Overall, these studies demonstrate unique effects of dietary PUFA and sex on brain oxylipins that have implications for dietary ALA requirements in rodents.
