Effects of n-3 polyunsaturated fatty acids and their derivatives on gene expression and cytokine production.

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Fatty acids were traditionally thought to represent intermediary metabolites involved in energy and substrate fluxes in several living organisms. However, it has now become very clear that increased cell and tissue fatty acid content can influence cell function through a variety of mechanisms including alterations in the physical property of the membrane as well as modulation of cell signalling pathways and gene expression. For example, we and others have observed that omega-3 or n-3 polyunsaturated fatty acid (n3-PUFA) supplementation using fish oil capsules substantially alters the gene expression profile of blood mononuclear cells in humans. Beneficial health effects of n-3 PUFAs have been consistently reported in human intervention studies with oily fish or fish oil that are rich in eicosapentanoic acid (EPA) and decohexaenoic acid (DHA). The effects are mainly attributable: 1) to the ability of n-3 PUFAs to modify the expression of transcription factors; and 2) to alterations in lipid mediators including resolvins and protectins. However, there are several limitations to human trials. First, it is relatively difficult to study the independent effect of EPA, DHA and their lipid mediators on gene expression. Another limitation of human trials is the access to target tissues. In the present research program, we want to develop cell culture models that will be used to perform in vitro studies addressing the cellular and molecular impact of n-3 PUFAs and their derivatives. Gene expression profiling or transcriptomics will be used in order to look at the independent effects of n-3 PUFAs and their lipid mediators on genes known to regulate cholesterol homeostasis and inflammatory mediators. In addition, the potential of n-3 PUFAs and their lipid-mediators to suppress inflammatory cytokine production will be studied. Such an integrated approach will help elucidate the underlying mechanisms explaining cellular and molecular changes attributable to n-3 PUFAs and pave the way for studies on the biological effects of bioactive lipids. Also, it will contribute to the training of highly qualified personnals in the growing field of nutrigenomics.