Effect of Dietary Fatty Acids on Inflammatory Gene Expression in Healthy Humans

• Published in: The Journal of biological chemistry 2009-06, Vol.284 (23), p.15400-15407
• Main Authors: Weaver, Kelly L., Ivester, Priscilla, Seeds, Michael, Case, L. Douglas, Arm, Jonathan P., Chilton, Floyd H.
• Format: Article
• Language: English
• Subjects: Dietary Fats - pharmacology; Dietary Fats, Unsaturated - pharmacology; Fatty Acids - blood; Fatty Acids - pharmacology; Fatty Acids, Omega-3 - pharmacology; Fish Oils - pharmacology; gamma-Linolenic Acid - pharmacology; Gene Expression Regulation - drug effects; Humans; Inflammation - genetics; Kinetics; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - physiology; Leukotriene B4 - blood; Lipids and Lipoproteins: Metabolism, Regulation, and Signaling; Neutrophils - drug effects; Neutrophils - physiology; Phosphatidylinositol 3-Kinases - drug effects; Phosphatidylinositol 3-Kinases - genetics; Plant Oils - pharmacology; Reverse Transcriptase Polymerase Chain Reaction; RNA - genetics; RNA - isolation & purification
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M109.004861

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 (ω6) to ω3 polyunsaturated fatty acids (PUFA) in circulation and in tissues. Increased ω6/ω3 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 ω6/ω3 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, NFκB, and inflammatory cytokines was measured by real-time PCR. A marked increase was seen in serum and neutrophil levels of long-chain ω3 PUFA concomitant with a reduction in the ω6/ω3 PUFA ratio (40%). The ex vivo capacity of stimulated neutrophils to produce leukotriene B4 was decreased by 31%. Expression of PI3Kα and PI3Kγ and the quantity of PI3Kα 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.