通过黑色皮质素依赖的mTOR激活控制来控制肝脏的ER平衡
Claus Brandt1, Hendrik Nolte2, Sinika Henschke1
1Department of Neuronal Control of Metabolism, Max Planck Institute for Metabolism Research, Gleueler Strasse 50, 50931 Cologne, Germany; Center for Endocrinology, Diabetes and Preventive Medicine (CEDP), University Hospital Cologne, Kerpener Strasse 26, 50924 Cologne, Germany; Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center for Molecular Medicine Cologne (CMMC), University of Cologne, Joseph-Stelzmann-Strasse 26, 50931 Cologne, Germany.
Cell
|November 17, 2018
概括
通过激活神经通路, 这一途径涉及下丘脑和交感神经系统,
科学领域:
- 代谢过程
- 神经内分泌学
- 细胞生物学
背景情况:
- 肝脏适应营养摄入对于新陈代谢平衡至关重要.
- 肝细胞内 (ER) 功能对于蛋白质合成和脂质代谢至关重要.
- 感官线索和代谢调节之间的相互作用尚未完全理解.
研究的目的:
- 研究感官对食物感知在早期肝脏适应过程中的作用.
- 阐明这些吸收前代谢反应中介的神经通路.
- 确定肝脏为营养物质的流入做好准备所涉及的关键分子信号级联.
主要方法:
- 使用光遗传和化学遗传技术在体内操纵下丘脑POMC神经元.
- 测量了肝脏mTOR信号,X盒绑定蛋白1 (Xbp1) 拼接和ER压力基因表达.
- 评估了酸胆合成和ER形态.
- 研究了黑色皮质素通路和交感神经活动 (SNA) 的作用.
主要成果:
- 仅仅通过感官感知食物就会触发肝脏的快速mTOR信号,Xbp1拼接,ER压力基因诱导和酸丁胆合成.
- 这些早期反应导致肝脏ER显著的形态重塑.
- 下丘脑POMC神经元的激活模仿了这些肝脏反应,而MC4R缺乏则减弱了它们.
- POMC神经元的激活增强了肝脏的SNA,而上腺素的使用复制了观察到的肝脏适应.
结论:
- 感官对食物的感知启动了肝脏的协调性食前后适应.
- 这种适应是由来自下丘脑POMC神经元的新型黑色皮质素-SNA-mTOR-Xbp1s轴介导的.
- 这些发现揭示了一种关键的神经机制,
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