Novel omega-3 fatty acid epoxides and the activation of cellular survival pathways

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Recent studies have reported that foods and oils containing high levels of omega-3 fatty acids have beneficial effects in patients with arthritis and cardiovascular disease. The mechanisms by which these dietary changes produce health benefits are unclear but it is known that omega-3 fatty acids can replace omega-6 and other fatty acids in cells; these omega-6 acids are more common in western diets. A number of enzymes in cells convert fatty acids to oxygenated derivatives and some of these have potent protective effects that allow cells to survive in the presence of toxic stimuli. We have found that epoxides formed from the omega-3 fatty acid stearidonic acid are extremely potent protective agents in cells - more so that epoxides from omega-6 acids like arachidonic acid. The present project seeks to identify omega-3 fatty acid epoxides with potent and long-lived beneficial effects in cells, relate these properties to those of omega-6 fatty acid epoxides and then understand how the omega-3 epoxides enhance cell survival. The findings will provide a rational basis from which to understand the beneficial effects of dietary modification already seen in clinical studies. By understanding the biochemical and molecular events in cells that are activated by omega-3 fatty acid epoxides we may be able to design therapies, most likely involving changes in dietary fat intake, that could benefit individuals with arthritic, cardiovascular and other conditions. Given the high incidence of these conditions in this country the potential impact of the findings from this project could be highly significant and are consistent with the national research priority healthy ageing.