利波卡林2调节线粒体脂体重塑,动力学和功能在棕色脂肪组织的雄性小鼠
Hongming Su1, Hong Guo1, Xiaoxue Qiu1
1Department of Food Science and Nutrition, University of Minnesota-Twin Cities, St. Paul, MN, 55108, USA.
Nature communications
|October 23, 2023
概括
利波卡林-2 (LCN2) 通过控制酸 (PA) 水平来调节棕色脂肪中的线粒体功能. 缺乏LCN2会影响能量代谢和线粒体动力学,影响肥胖和衰老.
科学领域:
- 线粒体生物学 线粒体生物学
- 细胞的新陈代谢
- 脂质生物化学 脂质生物化学
背景情况:
- 线粒体功能对于热性脂肪细胞的能量代谢至关重要,其损害与肥胖和衰老有关.
- 心脏脂素 (CL) 和酸 (PA) 调节线粒体膜,线粒体关联的细胞内网膜 (MAM) 是脂代谢的关键.
- 调节MAM脂代谢的调节者及其对线粒体功能的影响仍然在很大程度上是未知的.
研究的目的:
- 调查LCN2在MAM调节脂代谢中的作用.
- 了解LCN2如何影响棕色脂肪组织 (BAT) 中的线粒体功能和生物能量.
- 探索LCN2,PA和下游信号通路之间的联系.
主要方法:
- 使用Lcn2淘汰赛 (KO) 的雄性小鼠模型.
- 分析了线粒体的融合裂变动态.
- 在BAT中对线粒体脂 (CL,PA) 和等离子体原体进行了脂质组分析.
- 评估过氧体功能和mTOR信号通路活动.
主要成果:
- 在炎症和代谢刺激期间,LCN2结合PA,并被招募到MAM.
- 在BAT中,Lcn2缺乏会破坏线粒体的融合裂变平衡,并改变线粒体脂的链组成.
- Lcn2 KO小鼠显示CL水平发生变化 (LC-PUFA-CL增加,MUFA-CL减少),导致线粒体功能障碍.
- 在Lcn2KO小鼠中,线粒体功能障碍触发了补偿性过氧体激活和等离子体生物合成.
- 缺少Lcn2会改变PA的产生,影响PA调节的酶和mTOR通路.
结论:
- LCN2是线粒体脂体中链重塑的关键调节器,并影响线粒体生物能学.
- LCN2调节PA的产生及其下游信号,影响线粒体功能.
- 这些发现凸显了LCN2在维持能量平衡和线粒体健康方面的重要性,这对肥胖和衰老研究产生了影响.
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