氧酸通过调节肠肝轴来缓解非酒精性脂肪性肝病
Junliang Kuang1, Jieyi Wang1, Yitao Li2
1Center for Translational Medicine, Shanghai Key Laboratory of Diabetes Mellitus and Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China.
Cell metabolism
|August 17, 2023
概括
氧化胆酸 (HDCA) 是一种肠道微生物修饰的胆酸,在非酒精性脂肪肝疾病 (NAFLD) 中显示出治疗潜力. HDCA通过调节肠道微生物群和激活肝脏关键信号通路来缓解NAFLD.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 微生物组研究 微生物组研究
- 代谢性疾病 代谢性疾病
背景情况:
- 非酒精性脂肪肝 (NAFLD) 影响全球四分之一的人口.
- 宿主-肠道微生物群相互作用在NAFLD病变发生过程中越来越被认可.
- 胆汁酸 (BAs) 是肠-肝-微生物群轴信号传递的关键媒介.
研究的目的:
- 调查肠道微生物群修饰胆酸在NAFLD中的作用.
- 探索氧化胆酸 (HDCA) 在NAFLD治疗中的治疗潜力.
- 阐明HDCA对NAFLD影响背后的分子机制.
主要方法:
- 胆酸概况与NAFLD的存在和严重程度的相关性分析.
- 在NAFLD临床前小鼠模型中给予HDCA.
- 对肠道和肝脏基因表达和信号通路 (FXR,CYP7B1,PPARα) 的分析.
- 16S rRNA基因测序以评估肠道微生物群的组成.
主要成果:
- HDCA物种与NAFLD的存在和严重程度有负相关性.
- 在小鼠模型中,HDCA治疗改善了NAFLD.
- HDCA 抑制了肠道法纳索伊德X受体 (FXR) 和上调的肝CYP7B1.1.
- HDCA增加了Parabacteroides distasonis的丰富性,通过PPARα信号增强了脂质代谢.
- 治疗HDCA导致肝脏FXR的随后上调.
结论:
- 在治疗NAFLD方面,HDCA显示出显著的治疗潜力.
- HDCA通过一种双重机制发挥其有益作用,包括肠道微生物群调节和直接肝脏信号传递.
- HDCA同时激活肝脏CYP7B1和PPARα,为NAFLD提供了一种新的治疗策略.
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