Nrf2 pathway in vegetable oil-induced inflammation of large yellow croaker (Larimichthys crocea).

ABSTRACT

This study was conducted to investigate the effects and regulation of dietary vegetable oil (VO, enriched with α-linolenic acid [ALA] and linoleic acid [LNA]) on the nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor-κB (NF-κB) pathways in large yellow croaker. In vivo study showed that the VO diet significantly decreased the activity of antioxidant enzymes and antioxidant enzyme-related mRNA expression in the liver tissue, in comparison with the fish oil (FO) diet (P < 0.05). The suppression of antioxidant capacity might be due to the decrease of nuclear Nrf2 protein translocation, Nrf2 binding to antioxidant response element (ARE) sequences, and subsequently, antioxidant genes transcription as electrophoretic mobility shift assay (EMSA) and luciferase assay showed. VO-derivated ALA and LNA exerted a lower antioxidant capacity than FO-derivated DHA and EPA, characterized by significantly lower nucleus Nfr2 protein expression but significantly higher ROS production values in primary hepatocytes (P < 0.05). The pro-inflammatory genes (tumor necrosis factor α [TNFα] and interleukin 1ß [IL1ß]) expression was significantly higher in the liver tissue of fish fed the VO diet which might be due to the activation of the NF-κB pathway (P < 0.05). Knockdown of the Nrf2 gene negatively affected the anti-inflammatory effect of fatty acids by increasing the expression of TNFα and the IL1ß gene and nuclear p65 protein (P < 0.05). In general, the results indicated that dietary vegetable oil decreased antioxidant capacity but induced inflammatory responses through the Nrf2/NF-κB pathway.