Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8336590 | The Journal of Nutritional Biochemistry | 2016 | 10 Pages |
Abstract
Typically fatty acids (FA) exert differential immunomodulatory effects with n-3 [α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] and n-6 [linoleic acid (LA) and arachidonic acid (AA)] exerting anti- and pro-inflammatory effects, respectively. This over-simplified interpretation is confounded by a failure to account for conversion of the parent FA (LA and ALA) to longer-chain bioactive products (AA and EPA/DHA, respectively), thereby precluding discernment of the immunomodulatory potential of specific FA. Therefore, we utilized the Î6-desaturase model, wherein knockout mice (D6KO) lack the Fads2 gene encoding for the rate-limiting enzyme that initiates FA metabolism, thereby providing a model to determine specific FA immunomodulatory effects. Wild-type (WT) and D6KO mice were fed one of four isocaloric diets differing in FA source (9 weeks): corn oil (LA-enriched), arachidonic acid single cell oil (AA-enriched), flaxseed oil (ALA-enriched) or menhaden fish oil (EPA/DHA-enriched). Splenic mononuclear cell cytokine production in response to lipopolysaccharide (LPS), T-cell receptor (TCR) and anti-CD40 stimulation was determined. Following LPS stimulation, AA was more bioactive compared to LA, by increasing inflammatory cytokine production of IL-6 (1.2-fold) and TNFα (1.3-fold). Further, LPS-stimulated IFNγ production in LA-fed D6KO mice was reduced 5-fold compared to LA-fed WT mice, indicating that conversion of LA to AA was necessary for cytokine production. Conversely, ALA exerted an independent immunomodulatory effect from EPA/DHA and all n-3 FA increased LPS-stimulated IL-10 production versus LA and AA. These data definitively identify specific immunomodulatory effects of individual FA and challenge the simplified view of the immunomodulatory effects of n-3 and n-6 FA.
Keywords
EPAΔ6-desaturaseD6DTLRAPCALATCrLPSFBSArachidonic acidalpha-linolenic acidEicosapentaenoic aciddocosahexaenoic acidLinoleic acidfatty acid desaturase 2Polyunsaturated fatty acidinflammationToll-like receptorDHAFish oillong chainfetal bovine serumantigen presenting cellCytokinesphycoerythrinlipopolysaccharideFatty acid metabolismmajor histocompatibility complexMHCT-cell receptor
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Authors
Jennifer M. Monk, Danyelle M. Liddle, Daniel J.A. Cohen, Denis H. Tsang, Lyn M. Hillyer, Salma A. Abdelmagid, Manabu T. Nakamura, Krista A. Power, David W.L. Ma, Lindsay E. Robinson,