Nutrigenomic Approaches to Study the Effects of N-3 PUFA Diet in the Central Nervous System

Deficiencies in essential, mainly omega-3 and omega-6 (n-3, n-6) long chain polyunsaturated fatty acids (LC-PUFA) result in visual and cognitive impairment and disturbances in mental functions in animals and could be the main reason for the increasing incidence of different mental disorders in humans. Traditional approaches cannot give us a detailed picture on how dietary lipids exert their effects, because they focus on only a few genes or biomarkers. Dietary lipids not only influence the biophysical state of the cell membranes but, via direct and indirect routes, they also act on multiple pathways including signalling and gene and protein activities. Therefore, to understand the molecular basis of the effects and roles of n-3 PUFA in the central nervous system global screening techniques such as DNA- or protein microarrays were used to assess the changes, in a global way, at the transcriptome and at the proteome level. With DNA microarrays we found that cholesterol and fish oil (high in PUFA) diets altered the expression of several genes involved in raft formation and membrane protrusions. By using protein microarrays we detected a decreased concentration of protein kinase C beta, gamma, phospholipase C gamma and other changes in the expression level of proteins involved in the signal transduction pathway in the brain in response to high cholesterol diet. Besides the known cellular effects of lipid nutritions (changing eicosanoid make up, effects on membrane fluidity and raft stability) it is now evident that dietary lipids influence gene and protein activity levels, protein modifications and probably play important role in modulating protein aggregation.