SREBP1 是 CLOCK 的下游目标,调解了 HFD 诱导的 MAFLD 的自然发展
Ying Wang1, Jia Luo2, Weiqi Zhang1
1Health Science Center, Ningbo University, Ningbo, China.
概括
肝脏 肝脏是肝脏中的一个部分.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 时间生物学 时间生物学
- 分子生物学分子生物学
背景情况:
- 循环时钟的干扰与代谢功能障碍相关的脂肪肝疾病 (MAFLD) 有关.
- 在MAFLD病原发生过程中,肝脏昼夜时钟的下游目标仍然不清楚.
研究的目的:
- 研究肝脏昼夜时钟在调节MAFLD发展中的作用.
- 为了确定肝脏中核心昼夜系因子CLOCK的下游目标.
主要方法:
- 高脂肪饮食 (HFD) 在雄性小鼠中诱导了MAFLD.
- 在细胞模型 (老鼠和人类) 中,CLOCK knockdown 和过度表达.
- 在小鼠中使用rAAV8-CAG-EGFP-Clock传递进行体内验证.
主要成果:
- HFD导致体重增加,肝脏肥胖症,并减少肝脏的CLOCK表达.
- 时钟敲击增加了SREBP1和脂质积累;时钟过度表达减少了它们.
- 在体内,CLOCK过度表达通过降低SREBP1信号的调节,逆转了肝硬化症,甘油三和胆固醇水平.
结论:
- 肝脏昼夜因子CLOCK在调节MAFLD方面发挥着至关重要的作用.
- SREBP1信号传递是CLOCK参与MAFLD发展的关键下游目标.
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