title: Dietary oxidized fat activates the oxidative stress-responsive transcription factors NF-κB and Nrf2 in intestinal mucosa of mice.
abstract: OBJECTIVE
  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-κB 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.
  
  
  METHODS
  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.
  
  
  RESULTS
  After 6 days of treatment, mice were killed, intestinal mucosa was isolated, and nuclear concentration of NF-κB and Nrf2 and expression of NF-κB- and Nrf2-regulated oxidative stress-responsive genes were determined. Oxidized fat markedly increased nuclear concentration of NF-κB 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.
  
  
  CONCLUSIONS
  The activation of oxidative stress-sensitive pathways likely reflects an adaptive response of the intestinal mucosa to prevent oxidative damage to the intestinal mucosa.
authors.affiliation: Institute of Animal Nutrition and Nutrition Physiology, Justus-Liebig-University Gießen, Heinrich-Buff-Ring 26-32, 35392, Gießen, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Varady
authors.forename: Klaus
authors.initials: K
authors.lastname: Eder
authors.forename: Robert
authors.initials: R
authors.lastname: Ringseis
mesh_terms: D000449:Aldehyde Reductase / Q000235:genetics / Q000378:metabolism; D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage*; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000235:genetics* / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D015854:Up-Regulation; D000094765:Glutathione Peroxidase GPX1
chemical_list: D004041:Dietary Fats; D058851:GPI-Linked Proteins; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495636:Nfe2l2 protein, mouse; D047493:PPAR alpha; D047495:PPAR gamma; D000449:Aldehyde Reductase; D005979:Glutathione Peroxidase; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000581:Amidohydrolases; C022314:pantetheinase; D000094765:Glutathione Peroxidase GPX1; C000722068:Gpx1 protein, mouse