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Dietary n-3 long chain PUFA supplementation promotes a pro-resolving oxylipin profile in the brain.
Brain Behav Immun. 2019 02; 76:17-27.BB

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.

Authors+Show Affiliations

INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, 33076 Bordeaux, France; ITERG, Institut des corps gras, 33600 Pessac, France.Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA 02118, USA.Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, 33076 Bordeaux, France; Université de Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France.INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, 33076 Bordeaux, France; Université de Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France.INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, 33076 Bordeaux, France; Université de Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France.INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, 33076 Bordeaux, France; Université de Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France.INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, 33076 Bordeaux, France; Université de Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France.ITERG, Institut des corps gras, 33600 Pessac, France.INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, 33076 Bordeaux, France; Université de Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France.INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, 33076 Bordeaux, France; Université de Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France. Electronic address: corinne.joffre@inra.fr.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30086401

Citation

Rey, C, et al. "Dietary N-3 Long Chain PUFA Supplementation Promotes a Pro-resolving Oxylipin Profile in the Brain." Brain, Behavior, and Immunity, vol. 76, 2019, pp. 17-27.
Rey C, Delpech JC, Madore C, et al. Dietary n-3 long chain PUFA supplementation promotes a pro-resolving oxylipin profile in the brain. Brain Behav Immun. 2019;76:17-27.
Rey, C., Delpech, J. C., Madore, C., Nadjar, A., Greenhalgh, A. D., Amadieu, C., Aubert, A., Pallet, V., Vaysse, C., Layé, S., & Joffre, C. (2019). Dietary n-3 long chain PUFA supplementation promotes a pro-resolving oxylipin profile in the brain. Brain, Behavior, and Immunity, 76, 17-27. https://doi.org/10.1016/j.bbi.2018.07.025
Rey C, et al. Dietary N-3 Long Chain PUFA Supplementation Promotes a Pro-resolving Oxylipin Profile in the Brain. Brain Behav Immun. 2019;76:17-27. PubMed PMID: 30086401.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dietary n-3 long chain PUFA supplementation promotes a pro-resolving oxylipin profile in the brain. AU - Rey,C, AU - Delpech,J C, AU - Madore,C, AU - Nadjar,A, AU - Greenhalgh,A D, AU - Amadieu,C, AU - Aubert,A, AU - Pallet,V, AU - Vaysse,C, AU - Layé,S, AU - Joffre,C, Y1 - 2018/08/04/ PY - 2018/05/09/received PY - 2018/07/27/revised PY - 2018/07/30/accepted PY - 2018/8/8/pubmed PY - 2020/2/29/medline PY - 2018/8/8/entrez KW - 18-HEPE KW - DHA KW - EET KW - EPA KW - N-3 PUFA KW - Neuroinflammation KW - Oxylipin KW - TxB2 SP - 17 EP - 27 JF - Brain, behavior, and immunity JO - Brain Behav. Immun. VL - 76 N2 - 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. SN - 1090-2139 UR - https://www.unboundmedicine.com/medline/citation/30086401/Dietary_n_3_long_chain_PUFA_supplementation_promotes_a_pro_resolving_oxylipin_profile_in_the_brain_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0889-1591(18)30397-0 DB - PRIME DP - Unbound Medicine ER -