Chen Wang, Qiao Chu, Wenxiao Dong, Xin Wang, Wenjing Zhao, Xin Dai, Wentian Liu, Bangmao Wang, Tianyu Liu, Weilong Zhong, Changtao Jiang, Hailong Cao
High-fat diet (HFD) has long been recognized as risk factors for the development and progression of ulcerative colitis (UC), but the exact mechanism remained elusive. Here, HFD increased intestinal deoxycholic acid (DCA) levels, and DCA further exacerbated colonic inflammation. Transcriptome analysis revealed that DCA triggered ferroptosis pathway in colitis mice. Mechanistically, DCA upregulated hypoxia-inducible factor-2α (HIF-2α) and divalent metal transporter-1 (DMT1) expression, causing the ferrous iron ions accumulation and ferroptosis in intestinal epithelial cells, which was reversed by ferroptosis inhibitor ferrostatin-1...
April 18, 2024: Molecular Metabolism