Xu Ziying, Gao Yagang, Yu Zihui, Zhang Rui, Wang Ruikun, Li Shang, Wang Shuowen, Du Bing, Tian Ziyan, Huang Lijuan, Ding Zanbo, Yuan Jing
Capital Institute of Pediatrics, Beijing, China.
Clinical Laboratory Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Sci Rep. 2025 Jan 20;15(1):2487. doi: 10.1038/s41598-025-86547-1.
Aldehyde dehydrogenase 2 (Aldh2) Glu504Lys mutation, common in East Asians, is linked to various alcohol-related pathologies, notably fatty liver disease. Recent findings suggest that high ethanol-producing Klebsiella pneumoniae(HiAlc Kpn) exacerbates liver injury in non-alcoholic fatty liver disease (NAFLD). Our study investigated the combined effects of Aldh2 deficiency and HiAlc Kpn on NAFLD liver injury, transcriptome analyses to unearth potential mechanisms and therapeutic targets. In our controlled experiment with Aldh2-deficient mice, we induced fatty liver via alcohol and HiAlc Kpn gavage, followed by comprehensive analyses to detect gene expression and epigenetic changes. The results showed that Aldh2-deficient mice were particularly vulnerable to ethanol and HiAlc Kpn, with notable gene expression changes in key metabolic and liver injury pathways. Our analysis identified crucial differentially expressed genes (DEGs) and pathways, highlighting the significant roles of genes like Cyp8b1, Cyp7a1, and Ugt2b1 in liver metabolism and suggesting them as therapeutic targets. The study underscores the impact of Aldh2 deficiency and HiAlc Kpn on NAFLD progression, revealing potential therapeutic strategies. Despite these insights, further research is needed to clarify the systemic effects on aldehyde metabolism and the full implications of Aldh2 deficiency and HiAlc Kpn in liver injury.
乙醛脱氢酶2（Aldh2）的Glu504Lys突变在东亚人群中较为常见，与多种酒精相关疾病有关，尤其是脂肪肝疾病。最近的研究结果表明，高产乙醇的肺炎克雷伯菌（HiAlc Kpn）会加重非酒精性脂肪性肝病（NAFLD）中的肝损伤。我们的研究调查了Aldh2缺乏和HiAlc Kpn对NAFLD肝损伤的联合作用，通过转录组分析来揭示潜在机制和治疗靶点。在我们对Aldh2缺陷小鼠的对照实验中，通过酒精和HiAlc Kpn灌胃诱导脂肪肝，随后进行全面分析以检测基因表达和表观遗传变化。结果表明，Aldh2缺陷小鼠对乙醇和HiAlc Kpn特别敏感，关键代谢和肝损伤途径中存在显著的基因表达变化。我们的分析确定了关键的差异表达基因（DEG）和途径，突出了Cyp8b1、Cyp7a1和Ugt2b1等基因在肝脏代谢中的重要作用，并将它们作为治疗靶点。该研究强调了Aldh2缺乏和HiAlc Kpn对NAFLD进展的影响，揭示了潜在的治疗策略。尽管有这些见解，但仍需要进一步研究来阐明对醛代谢的全身影响以及Aldh2缺乏和HiAlc Kpn在肝损伤中的全部意义。
