Dietary n‐6 PUFA deprivation for 15 weeks alters expression and activity of enzymes of arachidonic acid and docosahexaenoic acid cascades in rat frontal cortex

n‐3 and n‐6 PUFAs are critical for brain function. Few studies have addressed the effects of n‐6 PUFAs deficient diet on brain, while many studies have examined n‐3 PUFA deficient diets. Previously, we reported that n‐3 PUFA deprivation for 15 weeks in rats increased the AA cascade enzyme ‐ cPLA 2 , sPLA 2 and COX‐2‐expressions, but decreased the DHA cascade enzyme, iPLA 2 . We also reported that 15 weeks of n‐6 PUFA deprivation increased DHA and decreased AA in brain. Based on these, we hypothesized that n‐6 PUFA dietary deprivation would increase the DHA cascade enzymes while decreasing the AA cascade enzymes. We fed male rats an n‐6 PUFA adequate or an n‐6 PUFA deficient diet for 15 weeks after weaning, and then measured enzyme activity, expression levels of PLA 2 s and expression of their transcription factors. Fifteen weeks of n‐6 PUFA deprivation significantly increased the enzyme activity, expression levels of iPLA 2 but decreased those of cPLA 2 and COX‐2. These effects correlated with an increased protein level of an iPLA 2 transcription factor SREBP‐1, and a decreased protein level of a cPLA 2 transcription factor, NF‐κB. Expression levels of sPLA 2 and COX‐1 were unchanged. The results suggest that dietary n‐6 PUFA deprivation leads to enzyme changes, at the transcriptional level, that would tend to reduce AA metabolic loss from brain, while increasing DHA metabolic loss. The increased iPLA 2 expression and decreased cPLA 2 and COX‐2 expression are in the opposite direction to changes caused by dietary n‐3 PUFA deprivation. Thus n‐3 and n‐6 PUFAs within brain have reciprocal effects, at the level of transcription, on expression of enzymes that regulate brain AA and DHA metabolism. This work was supported entirely by the Intramural Research Program of the NIH, National Institute on Aging.