在UFBP1上的Ufmylation通过调节肝脏内质网膜应激应变来缓解非酒精性脂肪性肝病

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Ziming Mao¹, Xiaowen Ma¹, Yu Jing¹

¹Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 201999, China.

Cell death & disease

|September 2, 2023

概括

UFBP1的Ufmylation通过减少ER压力和改善脂质代谢来保护免受非酒精性脂肪性肝病 (NAFLD) 的影响. 这一发现为NAFLD治疗提供了潜在的治疗目标.

科学领域:

生物化学生物化学
细胞生物学细胞生物学
肝病学肝病学是一种肝病学.

背景情况:

非酒精性脂肪性肝病 (NAFLD) 是一种普遍存在的疾病,其特点是肝脏脂肪积累和内质网膜 (ER) 压力,有效治疗方法有限.
Ufmylation是一种涉及Ubiquitin-fold修饰剂1 (UFM1) 的翻译后修饰,它调节了ER压力,可能在NAFLD病变发生过程中发挥作用.

研究的目的:

调查乌夫mylation在NAFLD发病过程中的作用,特别是其对UFM1结合蛋白1 (UFBP1) 的影响.
探索化影响NAFLD进展的潜在机制,并确定潜在的治疗点.

主要方法:

在NAFLD患者和模型肝脏中分析UFM1结合蛋白和ufmylation系统组件.
使用用自由脂肪酸 (FFA) 处理的肝细胞进行体外研究,以评估UFBP1的敲击和救援实验.
在高脂肪饮食 (HFD) 诱导的NAFLD小鼠模型中的体内研究,以评估ufmylation对UFBP1.1的影响.

主要成果:

在NAFLD肝脏中观察到化成分的表达增加,这表明对ER压力的适应性反应.
在实验室中除UFBP1会加剧脂质积累,而野生类型的UFBP1则挽救了这种效应.
在体内,UFBP1的化改善了HFD诱导的NAFLD小鼠的肥胖,肝硬化,失脂症,胰岛素耐药性和肝损伤.
UFBP1的化减轻了ER的压力,这与改善的肝脂生和胰岛素抵抗有关.

结论:

UFBP1的Ufmylation通过减轻ER压力和改善代谢功能障碍,对NAFLD起着保护作用.
针对UFBP1的化,为治疗NAFLD提供了一个有前途的治疗策略.

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