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

Brain Behav Immun. 2019 Feb;76:17-27. doi: 10.1016/j.bbi.2018.07.025. Epub 2018 Aug 4.

Abstract

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.

Keywords: 18-HEPE; DHA; EET; EPA; N-3 PUFA; Neuroinflammation; Oxylipin; TxB2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Cytokines / metabolism
  • Diet
  • Dietary Supplements
  • Fatty Acids
  • Fatty Acids, Omega-3 / metabolism*
  • Fatty Acids, Omega-3 / physiology
  • Fatty Acids, Omega-6
  • Fatty Acids, Unsaturated / metabolism
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Inflammation / metabolism
  • Lipopolysaccharides / adverse effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Models, Animal
  • Oxylipins / metabolism*

Substances

  • Cytokines
  • Fatty Acids
  • Fatty Acids, Omega-3
  • Fatty Acids, Omega-6
  • Fatty Acids, Unsaturated
  • Lipopolysaccharides
  • Oxylipins