Department of Gastrointestinal Surgery, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Guangdong province, China.
State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
J Nutr Biochem. 2022 Nov;109:109106. doi: 10.1016/j.jnutbio.2022.109106. Epub 2022 Jul 17.
A high-fat diet (HFD) is reported to exacerbate ulcerative colitis by inducing obesity, which conceals the effect of the diet itself. Ferroptosis, a type of regulated cell death induced by lipid hydroperoxides, has recently been reported in colitis. Here, we aimed to determine whether HFD affects ferroptosis and colitis progression in an obesity-independent manner. We subjected male C57BL/6J mice to either an HFD (60% fat diet) or isocaloric control diet (10% fat diet) for 4 weeks, followed by inducing colitis with 2.5% dextran sulfate sodium (DSS). Compared with the isocaloric control diet, non-obesogenic HFD reduced DSS-induced colonic mucosal injury, as shown by disease activity index, colon thickness, inflammatory infiltrations, and mucosal damage index; however, there were no differences in body weight, Lee's index, and omental fat weight between the two groups. HFD mice exhibited decreased lipid peroxidation and ferroptosis markers expression in colon tissues. Furthermore, a lipid mixture protected gut organoids and normal colonic epithelial cells from RSL3-induced ferroptosis. Mechanistically, the lipid mixture prevented glutathione deficiency by upregulating the cysteine transporter, solute carrier family seven member 11. Collectively, these findings suggest that an HFD ameliorates DSS-induced colitis through ferroptosis repression in an obesity-independent manner and provide new evidence to evaluate the effects of an HFD on colitis.
高脂肪饮食（HFD）通过诱导肥胖而加剧溃疡性结肠炎，这掩盖了饮食本身的作用。铁死亡，一种由脂质过氧化物诱导的调节性细胞死亡，最近在结肠炎中被报道。在这里，我们旨在确定 HFD 是否以肥胖不依赖的方式影响铁死亡和结肠炎的进展。我们使雄性 C57BL/6J 小鼠接受高脂肪饮食（60%脂肪饮食）或等热量对照饮食（10%脂肪饮食）4 周，然后用 2.5%葡聚糖硫酸钠（DSS）诱导结肠炎。与等热量对照饮食相比，非肥胖的 HFD 减少了 DSS 诱导的结肠黏膜损伤，表现为疾病活动指数、结肠厚度、炎症浸润和黏膜损伤指数；然而，两组之间的体重、Lee 指数和大网膜脂肪重量没有差异。HFD 小鼠的结肠组织中脂质过氧化和铁死亡标志物的表达减少。此外，脂质混合物保护肠道类器官和正常结肠上皮细胞免受 RSL3 诱导的铁死亡。从机制上讲，脂质混合物通过上调半胱氨酸转运蛋白、溶质载体家族 7 成员 11 来防止谷胱甘肽缺乏。总的来说，这些发现表明，HFD 通过肥胖不依赖的方式抑制铁死亡来改善 DSS 诱导的结肠炎，并为评估 HFD 对结肠炎的影响提供了新的证据。
