Wang Ning, Wang Huguo, Yao Hua, Wei Qin, Mao Xin-Min, Jiang Tao, Xiang Jing, Dila Na
Department of No. 1 Cadre Wards Medicine, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830011, P.R. China.
Exp Ther Med. 2013 Sep;6(3):635-640. doi: 10.3892/etm.2013.1214. Epub 2013 Jul 10.
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.
肥胖中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（TLR4）在肥胖相关炎症和胰岛素抵抗中起重要作用，但TLR4激活在肠道中的作用尚未得到研究。本研究的目的是探讨短期高脂饮食给药后小鼠肠道TLR4/NF-κB信号通路的激活情况，以及该信号通路在局部肠道炎症反应中的功能。研究了高脂饮食对饮食诱导的肥胖C57BL/6小鼠肠道组织中TLR4激活、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，高脂饮食诱导肠道组织中TLR4 mRNA和蛋白表达。随着高脂饮食给药天数的增加，TLR4/NF-κB信号通路激活逐渐增加，并在第7天达到峰值。此外，该信号通路的激活降低了肠道组织中PIκB表达水平，并增加了TNF-α和IL-6表达水平。我们的结果表明短期高脂饮食诱导肠道组织中TLR4/NF-κB信号通路激活，从而导致局部肠道低度炎症。这些数据增进了我们对肠道低度炎症所涉及分子事件的理解，肠道低度炎症可能是慢性全身性低度炎症的触发因素。
