Long-term supplementation with EPA and DHA changes the fatty acid profile of rat tissues, upregulates NRF2 expression and downregulates TGFβ expression

Abstract

We studied the influence of long-term treatment with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on the liver, and kidney lipogenesis, inflammation and antioxidative gene expression. Male Wistar rats were divided into three groups on the basis of the different n6/n3 fatty acid ratios achieved by using different dietary oil blends: the control (CON, n6/n3 ratio was ~7), the N6 group (n6/n3 ratio was ~50) and the DHA group (n6/n3 ~1). Treatment significantly influenced the fatty acid profile of the liver and kidney tissues. The most characteristic changes were an increased content of EPA and DHA in the DHA group in both tissues, of the kidney and liver. The expression of transforming growth factor beta (TGF-ß) was downregulated in the liver tissue by long-term EPA/DHA supplementation. This could be attributed to a decrease in the production of arachidonic acid-derived proinflammatory mediators, and an increase in EPA and DHA derived eicosanoids. DHA and EPA supplementation also significantly increased expression of the NRF 2 gene. This finding suggests that n3 PUFA could influence the activation of the NRF 2 pathway, which is important in cell antioxidative defense. In conclusion, we have shown that long-term dietary supplementation with DHA and EPA could influence lipid metabolism, inflammation and antioxidative defense. Therefore, the long-term addition of dietary DHA and EPA could potentially influence the most important pathological processes in aging.