帕迪4依赖性NETosis使饮食诱导的肠道过性成为可能,将dysbiosis转化为全身炎症和消化不良
Mattia Albiero1,2, Ludovica Migliozzi2,3, Carlotta Boscaro2,3
1Department of Surgery, Oncology and Gastroenterology, University of Padova, Padua, Italy.
Diabetes
|February 13, 2025
概括
氨基氨酸减小酶4 (PADI4) 驱动中性粒细胞外细胞陷 (NET) 的形成,将饮食诱导的微生物群变化与代谢功能障碍联系起来. 抑制PADI4可以防止肠道屏障破坏和代谢疾病.
科学领域:
- 免疫学 免疫学 免疫学
- 代谢过程中的代谢.
- 微生物组研究的研究.
背景情况:
- 中性粒细胞外细胞陷 (NETs),通过基氨酸减小酶4 (PADI4) 释放,可以传播炎症.
- 与肥胖相关的失糖症与脂肪组织中的NETosis有关.
- 高脂肪饮食 (HFD) 诱导了代谢功能障碍,炎症和NETosis.
研究的目的:
- 研究PADI4在调解饮食修饰微生物群对宿主新陈代谢影响中的作用.
- 确定PADI4依赖性NETosis是否有助于代谢性内毒性和肠道屏障功能障碍.
- 探索PADI4抑制作为饮食诱导的代谢疾病的治疗策略.
主要方法:
- 利用Padi4淘汰赛 (Padi4KO) 的小鼠和药物 PADI4 抑制.
- 向小鼠进行高脂肪饮食 (HFD),以诱导代谢功能障碍和炎症.
- 评估肠道屏障完整性,新陈代谢参数,肝脂肪症和全身炎症.
- 研究了从HFD养的小鼠移植到Padi4KO小鼠的微生物群的影响.
主要成果:
- 在小鼠中,HFD诱导了代谢不良,炎症和NETosis.
- 在保护免受HFD诱导的肝脏和脂肪炎症和改善新陈代谢的造血细胞中的 Padi4 缺失.
- 废除NETosis保留了肠道屏障功能,并减少了代谢性内毒性.
- Padi4KO小鼠得到了保护,免受HFD微生物群诱导的超透性和代谢障碍.
- 药理上的PADI4抑制模仿了PADI4KO的发现,改善了新陈代谢和减少了肝硬化.
结论:
- PADI4介导的NETosis作用于微生物群-肠道接口,导致超透性和细菌产品溢出.
- 这一过程对HFD的代谢后果有着显著的贡献.
- PADI4是一种可用药物的标,用于减轻不健康微生物群的代谢影响.
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