Research: Omega3/Omega6 ratio and Autoimmune disease.
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research-article
Effect of Dietary Fatty Acids on Inflammatory Gene Expression in Healthy Humans*
Kelly L. Weaver{ddagger}§, Priscilla Ivester§1, Michael Seeds{ddagger}, L. Douglas Case¶, Jonathan P. Arm||, and Floyd H. Chilton§
From the From the {ddagger}Department of Internal Medicine, Section on Molecular Medicine, and , Departments of §Physiology and Pharmacology and , ¶Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157 and the , ||Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115
ABSTRACT
Over the past 100 years, changes in the food supply in Western nations have resulted in alterations in dietary fatty acid consumption, leading to a dramatic increase in the ratio of omega-6 ({omega}6) to {omega}3 polyunsaturated fatty acids (PUFA) in circulation and in tissues. Increased {omega}6/{omega}3 ratios are hypothesized to increase inflammatory mediator production, leading to higher incidence of inflammatory diseases, and may impact inflammatory gene expression. To determine the effect of reducing the {omega}6/{omega}3 ratio on expression of inflammatory pathway genes in mononuclear cells, healthy humans were placed on a controlled diet for 1 week, then given fish oil and borage oil for an additional 4 weeks. Serum and neutrophil fatty acid composition and ex vivo leukotriene B4 production from stimulated neutrophils were measured at the start and end of the supplementation period and after a 2-week washout. RNA was isolated from mononuclear cells and expression of PI3K, Akt, NF{kappa}B, and inflammatory cytokines was measured by real-time PCR. A marked increase was seen in serum and neutrophil levels of long-chain {omega}3 PUFA concomitant with a reduction in the {omega}6/{omega}3 PUFA ratio (40%). The ex vivo capacity of stimulated neutrophils to produce leukotriene B4 was decreased by 31%. Expression of PI3K{alpha} and PI3K{gamma} and the quantity of PI3K{alpha} protein in mononuclear cells was reduced after supplementation, as was the expression of several proinflammatory cytokines. These data reveal that PUFA may exert their clinical effects via their capacity to regulate the expression of signal transduction genes and genes for proinflammatory cytokines.
Abbreviations: PUFA, polyunsaturated fatty acid • PBMC, peripheral blood mononuclear cell • FAME, fatty acid methyl ester • LT, leukotriene • EPA, eicosapentaenoic acid • DPA, docosapentaenoic acid • IL, interleukin • TNF, tumor necrosis factor • AA, arachidonic acid • DGLA, dihomo-{gamma}-linolenic acid • PI3K, phosphatidylinositol 3-kinase.
Received for publication, January 28, 2009 , and in revised form, April 6, 2009.
1To whom correspondence should be addressed: Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157. Tel.: 336-716-7388; Fax: 336-716-8501; E-mail: ivester@wfubmc.edu. |
