Although obesity is associated with inflammatory bowel disease (IBD), the underlying molecular mechanism still remains unclear. In this study, we evaluated the effects of high-fat diet (HFD)-induced obesity on the development of experimental colitis in mice. The C57BL/6 mice were fed with a HFD for 12 weeks to develop obesity. The concentrations of free fatty acids (FFA), triglycerides, and cholesterol in plasma were significantly increased in HFD-fed mice compared to low-fat diet (LFD)-fed mice. We found that HFD-induced obesity could exacerbate 2,4,6-trinitro-benzene-sulfonic acid (TNBS)-induced experimental colitis in mice resembling Crohn’s disease (CD). HFD-fed mice showed shorter colon length, higher clinical scores and histological scores, more production of mucosal tumor necrosis factor-α (TNF-α), and greater destruction of colonic epithelial barrier than LFD-fed mice after TNBS induction. HFD feeding also promoted reactive oxygen species (ROS) production in colonic epithelial cells, thus activating the pro-apoptotic pathway to damage colonic epithelial barrier induced by TNBS. After HCT116 cells were treated with palmitate acid (PA) and/or TNF-α for 24 h, the combination of PA and TNF-α increased ROS production, promoted mitochondrial dysfunction, and activated the pro-apoptotic pathway, but these effects were markedly attenuated by a ROS inhibitor. Taken together, these observations suggest that HFD-induced obesity promotes experimental colitis by increasing oxidative stress and mitochondrial dysfunction, which triggers the activation of pro-apoptotic pathway in the colon.

尽管肥胖与炎症性肠病（IBD）有关，但潜在的分子机制仍不清楚。在这项研究中，我们评估了高脂饮食（HFD）引起的肥胖对小鼠实验性结肠炎发展的影响。给C57BL / 6小鼠喂食HFD 12周以使其肥胖。与低脂饮食（LFD）喂养的小鼠相比，HFD喂养的小鼠血浆中的游离脂肪酸（FFA），甘油三酸酯和胆固醇的浓度显着增加。我们发现，HFD诱发的肥胖症可能会在类似于克罗恩病（CD）的小鼠中加剧2,4,6-三硝基苯磺酸（TNBS）诱发的实验性结肠炎。用HFD喂养的小鼠显示出较短的结肠长度，较高的临床评分和组织学评分，粘膜肿瘤坏死因子-α（TNF-α）产生更多，TNBS诱导后，与LFD喂养的小鼠相比，对结肠上皮屏障的破坏更大。HFD进食还可以促进结肠上皮细胞中活性氧（ROS）的产生，从而激活促凋亡途径，从而破坏TNBS诱导的结肠上皮屏障。用棕榈酸（PA）和/或TNF-α处理HCT116细胞24小时后，PA和TNF-α的组合增加了ROS的产生，促进了线粒体功能障碍，并激活了促凋亡途径，但是这些作用明显被ROS抑制剂减弱。综上所述，这些观察结果表明，HFD诱导的肥胖症通过增加氧化应激和线粒体功能障碍来促进实验性结肠炎，从而触发结肠中促凋亡途径的激活。HFD进食还可以促进结肠上皮细胞中活性氧（ROS）的产生，从而激活促凋亡途径，从而破坏TNBS诱导的结肠上皮屏障。用棕榈酸（PA）和/或TNF-α处理HCT116细胞24小时后，PA和TNF-α的组合增加了ROS的产生，促进了线粒体功能障碍，并激活了促凋亡途径，但是这些作用明显被ROS抑制剂减弱。综上所述，这些观察结果表明，HFD诱导的肥胖症通过增加氧化应激和线粒体功能障碍来促进实验性结肠炎，从而触发结肠中促凋亡途径的激活。HFD进食还可以促进结肠上皮细胞中活性氧（ROS）的产生，从而激活促凋亡途径，从而破坏TNBS诱导的结肠上皮屏障。用棕榈酸（PA）和/或TNF-α处理HCT116细胞24小时后，PA和TNF-α的组合增加了ROS的产生，促进了线粒体功能障碍，并激活了促凋亡途径，但是这些作用明显被ROS抑制剂减弱。综上所述，这些观察结果表明，HFD诱导的肥胖症通过增加氧化应激和线粒体功能障碍来促进实验性结肠炎，从而触发结肠促凋亡途径的激活。从而激活促凋亡途径，从而破坏TNBS诱导的结肠上皮屏障。用棕榈酸（PA）和/或TNF-α处理HCT116细胞24小时后，PA和TNF-α的组合增加了ROS的产生，促进了线粒体功能障碍，并激活了促凋亡途径，但是这些作用明显被ROS抑制剂减弱。综上所述，这些观察结果表明，HFD诱导的肥胖症通过增加氧化应激和线粒体功能障碍来促进实验性结肠炎，从而触发结肠中促凋亡途径的激活。从而激活促凋亡途径，从而破坏TNBS诱导的结肠上皮屏障。用棕榈酸（PA）和/或TNF-α处理HCT116细胞24小时后，PA和TNF-α的组合增加了ROS的产生，促进了线粒体功能障碍，并激活了促凋亡途径，但是这些作用明显被ROS抑制剂减弱。综上所述，这些观察结果表明，HFD诱导的肥胖症通过增加氧化应激和线粒体功能障碍来促进实验性结肠炎，从而触发结肠中促凋亡途径的激活。但是这些作用被ROS抑制剂明显减弱。综上所述，这些观察结果表明，HFD诱导的肥胖症通过增加氧化应激和线粒体功能障碍来促进实验性结肠炎，从而触发结肠中促凋亡途径的激活。但是这些作用被ROS抑制剂明显减弱。综上所述，这些观察结果表明，HFD诱导的肥胖症通过增加氧化应激和线粒体功能障碍来促进实验性结肠炎，从而触发结肠促凋亡途径的激活。