Dietary n-3 long chain PUFA supplementation promotes a pro-resolving oxylipin profile in the brain

C. Rey, J.c. Delpech, C. Madore, A. Nadjar, A.d. Greenhalgh, C. Amadieu, A. Aubert, V. Pallet, C. Vaysse, S. Layé, C. Joffre

Research output: Contribution to journalArticlepeer-review


The brain is highly enriched in long chain polyunsaturated fatty acids (LC-PUFAs) that display immunomodulatory properties in the brain. At the periphery, the modulation of inflammation by LC-PUFAs occurs through lipid mediators called oxylipins which have anti-inflammatory and pro-resolving activities when derived from n-3 LC-PUFAs and pro-inflammatory activities when derived from n-6 LC-PUFAs. However, whether a diet rich in LC-PUFAs modulates oxylipins and neuroinflammation in the brain has been poorly investigated. In this study, the effect of a dietary n-3 LC-PUFA supplementation on oxylipin profile and neuroinflammation in the brain was analyzed. Mice were given diets deficient or supplemented in n-3 LC-PUFAs for a 2-month period starting at post-natal day 21, followed by a peripheral administration of lipopolysaccharide (LPS) at adulthood. We first showed that dietary n-3 LC-PUFA supplementation induced n-3 LC-PUFA enrichment in the hippocampus and subsequently an increase in n-3 PUFA-derived oxylipins and a decrease in n-6 PUFA-derived oxylipins. In response to LPS, n-3 LC-PUFA deficient mice presented a pro-inflammatory oxylipin profile whereas n-3 LC-PUFA supplemented mice displayed an anti-inflammatory oxylipin profile in the hippocampus. Accordingly, the expression of cyclooxygenase-2 and 5-lipoxygenase, the enzymes implicated in pro- and anti-inflammatory oxylipin synthesis, was induced by LPS in both diets. In addition, LPS-induced pro-inflammatory cytokine increase was reduced by dietary n-3 LC-PUFA supplementation. These results indicate that brain n-3 LC-PUFAs increase by dietary means and promote the synthesis of anti-inflammatory derived bioactive oxylipins. As neuroinflammation plays a key role in all brain injuries and many neurodegenerative disorders, the present data suggest that dietary habits may be an important regulator of brain cytokine production in these contexts.
Original languageEnglish
Pages (from-to)17-27
JournalBrain, Behavior, and Immunity
Publication statusPublished - 4 Aug 2018


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