微生物代谢物脱氧醇酸介导的铁灭症加剧了高脂肪饮食引起的结肠炎症
Chen Wang1, Qiao Chu1, Wenxiao Dong1
1Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, National Key Clinical Specialty, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China.
Molecular metabolism
|April 20, 2024
概括
高脂肪饮食通过增加胆汁酸脱氧醇酸 (DCA) 来加剧性结肠炎,从而引发结肠中的细胞死亡途径铁亡. 这种机制涉及缺氧诱导因子-2α (HIF-2α) 并影响人类患者.
科学领域:
- 胃肠病学 胃肠病学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 高脂肪饮食 (HFD) 是性结肠炎 (UC) 发展和进展的已知危险因素.
- 连接HFD与UC病原体的精确分子机制仍然不完全理解.
研究的目的:
- 阐明HFD在UC中加剧结肠炎症的机制.
- 调查胆酸,特别是脱氧胆酸 (DCA) 和铁死在HFD诱导的UC中的作用.
主要方法:
- 在肠炎小鼠模型中进行的转录组分析,这些小鼠被食HFD.
- 研究DCA对铁亡,缺氧诱导因子-2α (HIF-2α) 和双价金属载体-1 (DMT1) 表达的作用.
- 使用特定于肠道的HIF-2α-null小鼠和ferrostatin-1 (一种ferroptosis抑制剂).
- 评估byak-angelicin对DCA诱导的炎症和铁亡的影响.
- 关联UC患者的脂肪摄入与疾病活性和铁亡标志物.
主要成果:
- HFD增加了肠道DCA水平,这加剧了结肠炎症.
- 在大肠炎小鼠中,DCA通过上调HIF-2α和DMT1来触发铁亡途径,导致铁的积累和细胞死亡.
- 在HIF-2α-null小鼠中,DCA导致的铁和大肠炎恶化被废除了.
- 比亚克-安吉利辛通过抑制HIF-2α上调来抵消DCA的促炎和促ferroptotic作用.
- 消费HFD的UC患者显示脂肪摄入量,疾病活性和铁亡标志物之间存在正相关性.
结论:
- 在UC中,HFD通过促进DCA诱导的铁死来加剧结肠炎症.
- DCA-HIF-2α-DMT1轴是饮食诱导的肠道炎症和细胞死亡的关键媒介.
- 这些发现为与饮食相关的UC胆汁酸失调提供了新的见解,并建议潜在的治疗点.
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