Most previous studies have focused on improved reference memory and recovery of whole brain docosahexaenoic acid [DHA, 22:6(n-3)] levels in DHA-deficient animals supplemented with fish oil (FO) or switched to an adequate DHA-enriched diet. The aims of this study were to determine whether reference and working memory performance can be enhanced in control male rats and improved in (n-3) fatty acid-deficient male rats given an FO supplement and whether brain DHA accumulation, deficiency, and recovery are region specific. From the embryo to postnatal d 140, 4 groups of rats were fed a nonpurified or sunflower oil-based (n-3) fatty acid-deficient diet alone or supplemented with (n-3) fatty acids from FO representing ∼0.3% of the energy source. The male rats were tested at postnatal d 102–130 for spatial learning memory performance in the Morris water maze. The fatty acid composition of different brain regions was analyzed by GC. Rats fed the (n-3) fatty acid-deficient diet showed significantly poorer reference and working memory, and FO supplementation partially rescued both memory performances. Furthermore, FO supplementation during brain development and adulthood in normal rats resulted in significant enhancement of both memories. Following dietary DHA repletion, the hippocampus and olfactory bulbs accumulated more DHA, were more resistant to dietary DHA deprivation, and showed better DHA recovery than the visual cortex, frontal cortex, and cerebellum. These results suggest that DHA is critical for the development and maintenance of learning memory performance.

Almost forty years ago, it was first hypothesized that an increased dietary intake of omega-3 polyunsaturated fatty acids (PUFA) from fish fat could exert protective effects against several pathologies. Decades of intense preclinical investigation have supported this hypothesis in a variety of model systems. Several clinical cardiovascular studies demonstrated the beneficial health effects of omega-3 PUFA, leading medical institutions worldwide to publish recommendations for their increased intake. However, particularly in recent years, contradictory results have been obtained in human studies focusing on cardiovascular disease and the clinical evidence in other diseases, particularly chronic inflammatory and neoplastic diseases, was never established to a degree that led to clear approval of treatment with omega-3 PUFA. Recent data not in line with the previous findings have sparked a debate on the health efficacy of omega-3 PUFA and the usefulness of increasing their intake for the prevention of a number of pathologies. In this review, we aim to examine the controversies on the possible use of these fatty acids as preventive/curative tools against the development of cardiovascular, metabolic, and inflammatory diseases, as well as several kinds of cancer.

A large body of evidence has emerged over the past years to show the critical role played by inflammation in the pathogenesis of several diseases including some cardiovascular, neoplastic, and neurodegenerative diseases, previously not considered inflammation-related. The anti-inflammatory action ofω-3 polyunsaturated fatty acids (PUFAs), as well as their potential healthy effects against the development and progression of the same diseases, has been widely studied by our and others’ laboratories. As a result, a rethinking is taking place on the possible mechanisms underlying the beneficial effects ofω-3 PUFAs against these disorders, and, in particular, on the influence that they may exert on the molecular pathways involved in inflammatory process, including the production of inflammatory cytokines and lipid mediators active in the resolving phase of inflammation. In the present review we will summarize and discuss the current knowledge regarding the modulating effects ofω-3 PUFAs on the production of inflammatory cytokines and proresolving or protective lipid mediators in the context of inflammatory, metabolic, neurodegenerative, and neoplastic diseases.