期刊
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
卷 32, 期 -, 页码 29-38出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jnutbio.2016.01.004
关键词
Polyunsaturated fatty acid; Cytokines; Inflammation; Fatty acid desaturase 2; Fatty acid metabolism
资金
- Natural Sciences and Engineering Research Council of Canada
- Canadian Institutes of Health Research [MOP-89,971]
- Canada Foundation for Innovation Leaders Opportunity Fund
- Ontario Research Fund
- Ontario Graduate Scholarship
- Canadian Breast Cancer Foundation-Ontario Region
Typically fatty acids (FA) exert differential immunomodulatory effects with n-3 [alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] and n-6 [linoleic add (IA) 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 discemment of the immunomodulatory potential of specific FA Therefore, we utilized the Delta 6-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 TNF alpha (1.3-fold). Further, LPS-stimulated IFN gamma 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. (C) 2016 The Authors. Published by Elsevier Inc.
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