Dietary oxidized fat activates the oxidative stress-responsive transcription factors NF-κB and Nrf2 in intestinal mucosa of mice

Oxidized fats are known to induce oxidative stress resulting in the up-regulation of antioxidant enzymes, with the underlying mechanism being unclear. It is known, however, that the response of tissues to oxidative stress is mediated by redox-sensitive transcription factors such as NF-kappa B and Nrf2. The aim of this study, therefore, was to test the hypothesis that ingestion of an oxidized fat causes activation of these transcription factors in the small intestinal mucosa. Female mice were randomly assigned to 2 groups of 12 mice each and administered orally by gavage either oxidized or fresh fat once per day. After 6 days of treatment, mice were killed, intestinal mucosa was isolated, and nuclear concentration of NF-kappa B and Nrf2 and expression of NF-kappa B- and Nrf2-regulated oxidative stress-responsive genes were determined. Oxidized fat markedly increased nuclear concentration of NF-kappa B and Nrf2 and transcript levels of oxidative stress-responsive genes, like aldo-keto reductase 1B8, vanin-1, glutathione peroxidase 1, and superoxide dismutase-1. In addition, oxidized fat increased the concentrations of PPAR-regulated genes. The activation of oxidative stress-sensitive pathways likely reflects an adaptive response of the intestinal mucosa to prevent oxidative damage to the intestinal mucosa.