Abstract
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.
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This work was supported by the guiding Plan of Natural Science Foundation of Liaoning Province of China (Grant No. 20170520275).
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Li, X., Li, X. Obesity Promotes Experimental Colitis by Increasing Oxidative Stress and Mitochondrial Dysfunction in the Colon. Inflammation 43, 1884–1892 (2020). https://doi.org/10.1007/s10753-020-01261-6
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DOI: https://doi.org/10.1007/s10753-020-01261-6