三 орто-克雷西尔酸盐通过mTOR激活和ER压力诱导诱导诱导肝肥胖症
1Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Ecotoxicology and environmental safety
|January 27, 2024
概括
三正酸 (TOCP) 通过通过内质网膜应激和mTOR信号传递增加脂质合成,导致肝损伤. 这些导致肝脏肥胖症的效应被特定的抑制剂逆转.
科学领域:
- 毒理学 毒理学 毒理学
- 肝病学 肝病学是一种肝病学.
- 分子生物学分子生物学
背景情况:
- 三甲酸 (TOCP) 是一种用于工业的有机化合物 (OP).
- 已知TOCP会引起神经毒性和生殖毒性.
- 之前,TOCP诱导肝毒性和影响脂质代谢的可能性尚不清楚.
研究的目的:
- 为了研究TOCP对肝细胞的影响.
- 为了检查TOCP对脂质代谢的影响.
- 为了阐明TOCP诱导的肝损伤背后的分子机制.
主要方法:
- 成年小鼠接受了单次口服剂量的TOCP (800 mg/kg).
- 分析了肝脏组织组织学和血清脂质含量.
- 评估了内等质网膜 (ER) 应激和mTOR途径抑制剂 (4-酸和拉巴胺素) 的影响.
- 测量了ER应激和mTOR信号生物标志物的表达水平 (GRP78,CHOP,p-mTOR).
主要成果:
- 暴露于TOCP导致小鼠肝脏组织中真空孔和脂质液滴增加.
- 在血清和肝脏中观察到三糖度的显著增加.
- 肝病理变化和高甘油被ER压力和mTOR抑制剂逆转.
- 在体内和体外,TOCP暴露改变了ER应激和mTOR途径生物标志物的表达.
结论:
- 在小鼠中,TOCP诱导肝脏肥胖症.
- 该机制涉及mTOR信号和ER压力的激活.
- 这种激活促进了新的脂质合成,导致肝脏脂肪的积累.
- 抑制ER压力和mTOR信号可以逆转TOCP诱导的肝毒性.
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