Obesity Promotes Experimental Colitis by Increasing Oxidative Stress and Mitochondrial Dysfunction in the Colon
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ORIGINAL ARTICLE
Obesity Promotes Experimental Colitis by Increasing Oxidative Stress and Mitochondrial Dysfunction in the Colon Xue Li1 and Xin Li
2,3
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 proapoptotic pathway in the colon.
Abstract—
KEY WORDS: obesity; high-fat diet; inflammatory bowel disease; oxidative stress; mitochondrial dysfunction.
INTRODUCTION
1
Institute of Health Sciences, China Medical University, Shenyang, 110122, China 2 Department of Chemistry, School of Fundamental Sciences, China Medical University, Shenyang, 110122, China 3 To whom correspondence should be addressed at Department of Chemistry, School of Fundamental Sciences, China Medical University, Shenyang, 110122, China. E-mail: [email protected]
Inflammatory bowel disease (IBD) is a chronic non-specific inflammatory disease, including Ulcerative colitis (UC) and Crohn’s disease (CD). Impaired intestinal epithelia barrier function is thought to be an important pathogenic factor leading to intestinal hyperpermeability in IBD [1]. Intestinal epithelial barrier is composed of intestinal epithelial cells (IECs) and intercellular tight junctions (TJ) [2]. Aberrant apoptosis of IECs or TJ structural disorder causes epithelial barrier disruption that can increase the epithelial
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Li, and Li permeability; promote bacteria, antigens, and toxins to enter the intestinal lumen; and subsequently trigger inflammatory reactions [3]. Recent study d
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