饮食诱导的RKIP下调会破坏PC/PE-ER平衡,从而推动MASLD
Mengjie Li1,2, Qian Ou1, Qiang Qin1
1Institute of Immunology and Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Nature communications
|December 12, 2025
概括
高脂肪饮食可以通过降低Raf激酶抑制蛋白 (RKIP) 来引起肝病. 这种蛋白质对于管理肝细胞功能和预防代谢功能障碍相关的脂肪性肝病 (MASLD) 进展至关重要.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 肝病学 肝病学是一种肝病学.
背景情况:
- 高脂肪饮食 (HFD) 是代谢功能障碍相关的脂肪性肝病 (MASLD) 的重要危险因素.
- 连接饮食脂肪摄入与MASLD肝功能障碍的精确分子机制尚未完全理解.
- 了解这些途径对于开发有效的治疗策略至关重要.
研究的目的:
- 阐明拉夫酶抑制蛋白 (RKIP) 在饮食诱导的MASLD病变发生中的作用.
- 调查RKIP影响肝脂代谢和内 плазма网膜 (ER) 恒常性的分子机制.
- 确定RKIP作为MASLD预防的潜在治疗目标.
主要方法:
- 在MASLD患者和HFD养的雄性小鼠中分析RKIP表达.
- 通过脂肪酸吸收和S-palmitoylation对RKIP调节的研究.
- 通过m6ARNA结合对PEMT翻译中的RKIP作用的评估.
- 检查肝细胞特异性RKIP枯竭对肝肥胖症和ER压力的影响.
主要成果:
- 在MASLD患者和HFD养的雄性小鼠中,肝脏RKIP的下调.
- 脂肪酸的吸收抑制RKIP S-palmitoylation,导致其与ER相关的降解.
- RKIP促进YTHDF1与m6A修饰的PEMTmRNA结合,促进PEMT翻译.
- RKIP的耗尽加剧了PC/PE不平衡和ER压力,恶化了MASLD.
- RKIP蛋白水平与PEMT正相关,但与MASLD严重程度相反.
结论:
- 低调RKIP是饮食诱导的MASLD的一个关键细胞机制,由HFD和脂肪酸吸收驱动.
- 该HFD-RKIP-PEMT通路关键调节肝脏ER平衡和脂质新陈代谢.
- 在预防和治疗MASLD方面,RKIP是一个有前途的治疗标.
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