Dietary n-3 long chain PUFA supplementation promotes a pro-resolving oxylipin profile in the brain
Brain, Behavior, and Immunity. 2019-02-01; 76: 17-27
DOI: 10.1016/j.bbi.2018.07.025
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1. Brain Behav Immun. 2019 Feb;76:17-27. doi: 10.1016/j.bbi.2018.07.025. Epub 2018
Aug 4.
Dietary n-3 long chain PUFA supplementation promotes a pro-resolving oxylipin
profile in the brain.
Rey C(1), Delpech JC(2), Madore C(3), Nadjar A(4), Greenhalgh AD(4), Amadieu
C(4), Aubert A(4), Pallet V(4), Vaysse C(5), Layé S(4), Joffre C(6).
Author information:
(1)INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, 33076 Bordeaux, France;
ITERG, Institut des corps gras, 33600 Pessac, France.
(2)Department of Pharmacology and Experimental Therapeutics, Boston University
School of Medicine, Boston, MA 02118, USA.
(3)Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical
School, Boston, MA 02115, USA.
(4)INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, 33076 Bordeaux, France;
Université de Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France.
(5)ITERG, Institut des corps gras, 33600 Pessac, France.
(6)INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, 33076 Bordeaux, France;
Université de Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France.
Electronic address:.
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.
Copyright © 2018 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.bbi.2018.07.025
PMID: 30086401