通过CdtB诱导的线粒体压力和脂质代谢重编程,Helicobacter hepaticus促进了肝脏肥胖症
Shanhao Jin1,2, Liqi Zhu3,4, Ruoyu Bao1,2
1Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou, China.
Nature communications
|August 26, 2025
概括
肝炎细菌感染,特别是其CdtB毒素,通过损害线粒体和破坏脂质代谢导致肝脏脂肪的积累. 中和CdtB为MASLD提供了一个潜在的治疗策略.
科学领域:
- 微生物学
- 肝病学
- 分子生物学
背景情况:
- 宿主-病原体相互作用与代谢功能障碍相关的脂肪性肝病 (MASLD) 等非传染性疾病有关.
- 在MASLD患者中存在Helicobacter hepaticus (H.
研究的目的:
- 调查H. hepaticus感染和肝脂症之间的因果关系.
- 阐明H. hepaticus诱导肝细胞中的脂质沉积的分子机制.
主要方法:
- 在体内和体外的实验涉及H. hepaticus感染和CdtB过度表达.
- 线粒体功能测定,脂质代谢分析和分子通路调查 (ROS,mTORC1,SREBP1,NONO).
- 使用小鼠模型和分析人类MASLD肝脏组织的体内研究.
主要成果:
- 肝炎感染或CdtB过度表达导致肝细胞中显著的脂质沉积.
- CdtB转移到线粒体,抑制了呼吸复合体V的活动,并导致线粒体损伤.
- 确定了CdtB-线粒体ROS-mTORC1-SREBP1轴和NONO介导的SREBP1核定位是推动脂质发生的关键途径.
- 在小鼠中,CdtB的中和改善了肝脂症.
- 在MASLD患者的肝脏组织中检测到H.
结论:
- 通过线粒体功能障碍和代谢途径干扰诱导肝脂症的关键因素是H. hepaticus CdtB.
- 对于H. hepaticus相关的MASLD,CdtB是一个潜在的治疗点.
- 肝炎感染与MASLD发生/进展之间存在相关性.
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