Expression and activity of the TLR4/NF-κB signaling pathway in mouse intestine following administration of a short-term high-fat diet.
Expression and activity of the TLR4/NF-κB signaling pathway in mouse intestine following administration of a short-term high-fat diet.
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DOI：
10.3892/etm.2013.1214
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发表时间：
2013-09
影响因子：
2.7
通讯作者：
Dila N
中科院分区：
文献类型：
--
作者：
Wang N;Wang H;Yao H;Wei Q;Mao XM;Jiang T;Xiang J;Dila N
肥胖者的胰岛素抵抗与慢性全身性低度炎症相关。尽管已经表明肝脏、肌肉和脂肪组织中的Toll样受体4（TLR 4）在肥胖相关炎症和胰岛素抵抗中起重要作用，但尚未研究TLR 4在肠中活化的作用。本研究旨在探讨短期高脂饮食对小鼠肠道TLR 4/NF-κB信号通路的激活及其在肠道局部炎症反应中的作用。研究高脂饮食对肥胖C57 BL/6小鼠肠组织中TLR 4活化、NF-κB和磷酸化IκB（PIκB）活性以及肿瘤坏死因子（TNF）-α和IL-6表达的影响。结果表明，高脂饲料诱导了小肠组织TLR 4 mRNA和蛋白的表达。TLR 4/NF-κB信号通路的激活随着高脂饮食给药天数的增加而逐渐增加，并在第7天达到峰值。此外，信号通路的激活降低了肠组织中PIκB的表达水平，并增加了TNF-α和IL-6的表达水平。我们的研究结果表明，短期高脂饮食会诱导肠道组织TLR 4/NF-κB信号通路的激活，从而导致局部肠道低度炎症。这些数据提高了我们对肠道低度炎症分子事件的理解，肠道低度炎症可能是慢性全身性低度炎症的触发因素。
Insulin resistance in obesity is associated with chronic systemic low-grade inflammation. Although it has been shown that Toll-like receptor 4 (TLR4) in the liver, muscle and adipose tissue plays an important role in obesity-associated inflammation and insulin resistance, the effect of TLR4 activation in the intestine has not been investigated. The aim of this study was to explore the activation of the mouse intestinal TLR4/NF-κB signaling pathway following the administration of a short-term high-fat diet, as well as the function of the signaling pathway in the local enteric inflammatory response. The effect of the high-fat diet on TLR4 activation, NF-κB and phosphorylated IκB (PIκB) activity, and tumor necrosis factor (TNF)-α and IL-6 expression in the intestinal tissues of diet-induced obese C57BL/6 mice was investigated. The results demonstrated that the high-fat diet induced TLR4 mRNA and protein expression in intestinal tissues. TLR4/NF-κB signaling pathway activation gradually increased as the number of days of high-fat diet administration increased, and peaked on day 7. Additionally, activation of the signaling pathway reduced PIκB expression levels and increased TNF-α and IL-6 expression levels in intestinal tissues. Our results demonstrated that a short-term high-fat diet induces activation of the TLR4/NF-κB signaling pathway in intestinal tissues, which causes local intestinal low-grade inflammation. These data improve our understanding of the molecular events involved in intestinal low-grade inflammation, which may be the triggering factor for chronic systemic low-grade inflammation.
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