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Influence of in vivo polyunsaturated fatty acid supplementation on expression of proximal signal transduction genes in human mononuclear cells
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.155.5
Subject(s) - polyunsaturated fatty acid , peripheral blood mononuclear cell , signal transduction , pi3k/akt/mtor pathway , fish oil , western blot , gene expression , protein kinase b , in vivo , biology , fatty acid desaturase , fatty acid , gene , chemistry , endocrinology , medicine , biochemistry , in vitro , fishery , fish <actinopterygii> , microbiology and biotechnology
A primary mechanism by which polyunsaturated fatty acids (PUFA) may have their potent effects on inflammatory disorders is by regulation of the expression of inflammatory genes. The purpose of the current study was to alter levels of n‐6 and n‐3 PUFA in humans and determine the effect on gene expression in circulating mononuclear cells. Healthy adults were placed on a background diet for 5 weeks, and given fish oil (775 mg EPA) and borage oil (831 mg GLA) supplements daily for 4 weeks. Blood was drawn weekly and fatty acid profiles in circulation were determined by gas chromatography. At the end of the supplementation period, long chain n‐6 to n‐3 fatty acid ratios shifted from greater than 20:1 to approximately 5:1. Mononuclear cells were isolated from whole blood and RNA and protein were extracted. Quantitative real‐time RT PCR showed a decrease in several genes that play a role in early signal transduction: PI3Kα (down 56%), PI3Kγ (down 66%) and Akt (down 57%) Expression of the inflammatory cytokines IL‐8 and IL‐23 was also decreased. Akt activation was studied by measuring the level of pAkt (S473) by Western blot and pAkt protein levels reflected a decrease following the supplementation period. These data support the hypothesis that circulating levels of PUFA may have their potent effects via their capacity to alter the expression of proximal genes critical to signal transduction pathways.