Dietary omega-3 (n-3) and omega-6 (n-6) fatty acids as novels activators of the anti-oxidant response

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We propose to leverage existing expertise and model systems we have created, to determine whether dietary omega-3 (n-3) and omega-6 (n-6) fatty acids activate the NRF2-dependent antioxidant response and as a result prevent neurodegeneration. Our focus is on the n-3 and n-6 fatty acids that have been associated with reduced risk of neurodegeneration in population cohort studies. The mechanism behind this correlation is unknown, yet determining which fatty acids elicit this effect and the mechanism responsible is of strategic value to the oil manufacturing industry. We hypothesize that this effect is due to the ability of n-3 and n-6 fatty acids to activate the NRF2 transcription factor, the master regulator of the cells anti-oxidant response pathway. Our goals are to determine 1) whether dietary n-3 and n-6 fatty acids activate the NRF2 response, 2) the mechanism underlying this effect, 3) whether the effect is dependent on single n-3/n-6 fatty acid species or complex dietary fatty acid intake and finally 4) whether this activity inhibits neurodegenerative-signaling cascades. To achieve these goals we will employ a combination of in vitro screening techniques as well as in vivo animal based dietary studies. This will allow for assessment of NRF2 activation in human neurons as well as measure the effect of dietary n-3 and n-6 fatty acid intake on neurodegenerative indices. To relate this work to the dietary trends within the Canadian population we have partnered with two agricultural industry representatives. Soy20/20 has acquired detailed population based information on oil consumption patterns amongst diverse sub groups of the Canadian population. This will allow us to translate our findings to actual Canadian dietary consumption patterns, and identify those oils whose fatty acid profiles correlate most highly with NRF2 activation. The Grain Farmers of Ontario influences the types of crops that are grown for specific purposes (ie industrial application verses consumption). Partnering with GFO will facilitate the translation of our findings into specific numbers of bushels of crops that are grown for dietary consumption, both increasing market share and providing value added dietary benefit to Canadians.