Institute of Animal Nutrition and Nutrition Physiology, Justus-Liebig-University Gießen, Heinrich-Buff-Ring 26-32, 35392, Gießen, Germany.
Eur J Nutr. 2011 Dec;50(8):601-9. doi: 10.1007/s00394-011-0181-8. Epub 2011 Mar 10.
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.
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-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.
The activation of oxidative stress-sensitive pathways likely reflects an adaptive response of the intestinal mucosa to prevent oxidative damage to the intestinal mucosa.
已知氧化脂肪会引起氧化应激,导致抗氧化酶的上调,但其潜在机制尚不清楚。然而,已知组织对氧化应激的反应是由 NF-κB 和 Nrf2 等氧化还原敏感转录因子介导的。因此,本研究的目的是检验以下假设,即摄入氧化脂肪会导致小肠黏膜中这些转录因子的激活。
将雌性小鼠随机分为两组,每组 12 只,每天通过灌胃分别给予氧化或新鲜脂肪。
治疗 6 天后,处死小鼠,分离肠黏膜,测定核内 NF-κB 和 Nrf2 的浓度以及 NF-κB 和 Nrf2 调节的氧化应激反应基因的表达。氧化脂肪显著增加了核内 NF-κB 和 Nrf2 的浓度以及氧化应激反应基因的转录水平,如醛酮还原酶 1B8、vanin-1、谷胱甘肽过氧化物酶 1 和超氧化物歧化酶 1。此外,氧化脂肪增加了 PPAR 调节基因的浓度。
氧化应激敏感途径的激活可能反映了小肠黏膜的适应性反应,以防止氧化损伤。