油酸通过减轻自功能障碍来改善肝脏脂毒性损伤
Xiaohong Liu1, Xiaoyu Li2, Shan Su1
1Department of Clinical Nutrition and Key Laboratory of Transplant Engineering and Immunology, NHFPC, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, PR China.
油酸 (OA) 通过通过TFEB调节溶酶体功能来改善非酒精性脂肪肝 (NAFLD) 的自功能障碍. 这保护肝细胞免受脂毒性和内质网膜压力.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 细胞生物学 细胞生物学
- 代谢疾病 代谢疾病
背景情况:
- 非酒精性脂肪性肝病 (NAFLD) 的发病包括和脂肪酸 (SFAs) 的脂毒性.
- 不和脂肪酸 (UFA),如油脂酸 (OA),表现出对SFA诱导的肝损伤的保护作用.
- 在NAFLD中调节自的OA的作用仍然在很大程度上未被探索.
研究的目的:
- 研究肝细胞中OA介导的自细胞调节的机制.
- 在小鼠模型中评估OA对NAFLD的保护作用.
主要方法:
- 在体外:用棕酸 (PA) /胺 (TM) 和/或OA处理的HepG2,L-02和AML12细胞.
- 在体内:高脂肪饮食 (HFD) 诱导的NAFLD模型在C57/BL6小鼠中,HFD部分被橄油所取代.
- 评估了细胞活力,细胞亡,内质网膜 (ER) 应激,自标志物和TFEB核转位.
主要成果:
- 通过降低TFEB核转位和CTSB活性,PA/TM诱导了肝细胞的亡和自功能障碍.
- OA缓解了PA / TM诱导的亡和自功能障碍,并恢复自减少了ER压力.
- 在HFD养小鼠的橄油补充剂逆转了NAFLD,改善了肥胖症并减少了自功能障碍,ER压力和亡.
结论:
- 油酸在脂毒性和ER压力环境中有效改善自功能障碍.
- 通过TFEB通过OA调节溶酶体功能障碍是NAFLD的关键保护机制.
- 针对ER压力自轴为NAFLD提供了一个潜在的治疗策略.
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