Integrated multi-omics analysis of liver metabolic dysregulation in ACE2 knockout mice

This study reveals the molecular mechanisms of liver metabolic dysregulation in ACE2 knockout (ACE2KO) mice through multi-omics analysis. ACE2 deficiency exacerbates lipid accumulation, disrupts RAS balance, and induces hepatocyte injury and inflammation. Integrated multi-omics analysis identified numerous differentially expressed genes, proteins, and metabolites, highlighting the PPAR signaling pathway as a central regulatory hub. ACE2 deletion also impairs detoxification and antioxidant balance, creating a self-reinforcing oxidative injury cycle. These findings provide new insights into the mechanisms and therapeutic targets of ACE2-related liver diseases. Overall design: RNA-seq profiling of 8-week-old male ACE2 knockout (ACE2KO) mice and age-matched C57BL/6J wild-type control mice.

本研究通过多组学分析，揭示了血管紧张素转换酶2（Angiotensin-converting enzyme 2, ACE2）敲除（ACE2KO）小鼠肝脏代谢失调的分子机制。ACE2缺失会加剧脂质蓄积、破坏肾素-血管紧张素系统（renin-angiotensin system, RAS）平衡紊乱，诱导肝细胞损伤与炎症。整合多组学分析鉴定出大量差异表达基因、蛋白质与代谢物，并明确过氧化物酶体增殖物激活受体（peroxisome proliferator-activated receptor, PPAR）信号通路作为核心调控枢纽。ACE2缺失还会削弱机体解毒功能与抗氧化平衡，形成自我强化的氧化损伤循环。本研究结果为ACE2相关肝脏疾病的发病机制与治疗靶点提供了全新见解。实验总体设计：对8周龄雄性ACE2敲除（ACE2KO）小鼠与同月龄C57BL/6J野生型对照小鼠开展RNA测序（RNA-seq）转录组分析。