杆菌感染加剧了乳化驱动的WTAP介导的肝肥胖症6 一种修改
Han Chen1,2, Zi Wang1,2, Yan Wang1,2
1Department of Gastroenterology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.
Gut microbes
|December 12, 2025
概括
杆菌感染通过增加RNA修饰中的关键蛋白质WTAP,使脂肪肝疾病恶化. 这一途径涉及乳酸并影响GLUT3,这表明代谢功能障碍相关的脂肪肝疾病的新治疗点.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 分子生物学分子生物学
- 微生物学 微生物学
背景情况:
- 杆菌 (H. pylori) 感染与胃外疾病有关,例如代谢功能障碍相关的脂肪肝疾病 (MASLD).
- 对于H. pylori影响MASLD的确切机制尚不清楚.
研究的目的:
- 调查H. pylori感染在恶化肝脏代谢障碍中的作用.
- 为了阐明背后的分子机制 H. pylori 诱导的肝硬化和胰岛素抵抗.
主要方法:
- 使用细胞模型 (HepG2) 和高脂肪饮食 (HFD) 诱导的小鼠模型进行了体外和体内实验.
- 对m6A修饰,WTAP表达,乳酸积累,H3K18乳化和GLUT3mRNA稳定性的分析.
- 基因淘汰和过度表达研究以评估功能影响.
主要成果:
- H. pylori 感染增加了肝脂沉积和胰岛素抵抗.
- 由H. pylori增加WTAP的调节促进了肝脏脂肪,减少了脂肪酸氧化 (FAO) 和氧化酸化 (OXPHOS).
- 乳酸积累通过H3K18乳化诱导WTAP上调,影响WTAP部位 (K99,K134) 并通过一个m6A-YTHDF1-依赖的通路调节GLUT3mRNA稳定性,为乳酸制造一个积极的反循环.
结论:
- 乳酸驱动的WTAP介导的RNA m6A修饰在H.pylori感染中显著加剧肝硬化症.
- 对于MASLD治疗考虑,H. pylori的状态至关重要.
- WTAP-YTHDF1-GLUT3轴为MASLD进展提供了一个潜在的治疗点.
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