Obesity Promotes Experimental Colitis by Increasing Oxidative Stress and Mitochondrial Dysfunction in the Colon

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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Funding

This work was supported by the guiding Plan of Natural Science Foundation of Liaoning Province of China (Grant No. 20170520275).

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Correspondence to Xin Li.

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Li, X., Li, X. Obesity Promotes Experimental Colitis by Increasing Oxidative Stress and Mitochondrial Dysfunction in the Colon. Inflammation (2020). https://doi.org/10.1007/s10753-020-01261-6

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KEY WORDS

  • obesity
  • high-fat diet
  • inflammatory bowel disease
  • oxidative stress
  • mitochondrial dysfunction