由线粒素控制的线粒体动力学调节Agrp神经元活动和饮食诱导的肥胖症
Marcelo O Dietrich1, Zhong-Wu Liu, Tamas L Horvath
1Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035, Brazil.
Cell
|October 1, 2013
概括
在agouti相关蛋白 (Agrp) 神经元中的线粒体动力学调节能量平衡. 在Agrp神经元中破坏线粒体融合会影响神经元活动,并减少高脂肪饮食的体重增加.
科学领域:
- 细胞生物学 细胞生物学
- 神经科学是一个神经科学.
- 代谢过程中的代谢.
背景情况:
- 线粒体对于细胞能量代谢和完整性至关重要.
- 阿古蒂相关蛋白 (Agrp) 神经元是调节食欲的关键氧化细胞.
- 线粒体动力学,包括融合和裂变,对于细胞功能至关重要.
研究的目的:
- 为了研究Agrp神经元在不同养状态中的线粒体动态的作用.
- 确定干扰Agrp神经元中的线粒体融合蛋白 (Mfn1,Mfn2) 的影响.
- 阐明Agrp神经元线粒体动力学对全身能量代谢的贡献.
主要方法:
- 分析了Agrp和亲opiomelanocortin (POMC) 神经元在不同养状态中的线粒体数量和大小.
- 在Agrp神经元中,细胞特异性的线粒素1 (Mfn1) 或线粒素2 (Mfn2) 的降解.
- 对Agrp神经元活动的电生理记录和ATP水平的评估.
- 评估高脂肪饮食 (HFD) 的淘汰赛小鼠的体重增加和脂肪质量.
主要成果:
- 线粒体数量减少,而Agrp神经元的大小增加,从禁食到过度养状态,POMC神经元发生相反的变化.
- 在Agrp神经元中Mfn1或Mfn2的敲除改变了线粒体形态,并在HFD期间损害了神经元的电活动.
- 给予ATP可以逆转Agrp神经元的电活动受损.
- 患有Agrp特异性Mfn1或Mfn2淘汰的小鼠在HFD上显示体重增加减少和脂肪质量减少.
结论:
- 由Mfn1和Mfn2调节的线粒体动力学在Agrp神经元功能中起着至关重要的作用.
- 在Agrp神经元中的这些线粒体变化是细胞类型的特异性,对养状态有反应.
- 在Agrp神经元中的Mfn1和Mfn2对于全身能量代谢和体重控制的中央调节至关重要.
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