肝脏时钟调整了骨肌肉中的转录节奏,以调节线粒体功能
Valentina Sica1, Tomoki Sato2, Ioannis Tsialtas3,4
1Universitat Pompeu Fabra (UPF), Department of Medicine and Life Sciences (MELIS), 08003 Barcelona, Spain.
bioRxiv : the preprint server for biology
|February 3, 2025
概括
肝脏的时钟与骨肌肉沟通,调节大约三分之一的肌肉基因节律,影响能量生产. 这种双向通路突显了肝脏时钟在微调肌肉新陈代谢中的作用.
科学领域:
- 时间生物学 时间生物学
- 代谢调节 代谢调节 代谢调节
- 内分泌学 在内分泌学.
背景情况:
- 昼夜时钟协调了平衡的生理过程.
- 组织特定的时钟之间的相互作用,如肝脏和骨肌肉,尚未完全理解.
- 之前的研究表明肌肉时钟会影响肝脏新陈代谢,但相反的情况是未知的.
研究的目的:
- 为了研究肝脏时钟是否调节骨肌肉的转录节奏.
- 探索肝脏和肌肉之间的双向通信. 昼夜时钟.
- 确定代谢性疾病的潜在治疗点.
主要方法:
- 使用肝细胞特异性Bmal1淘汰赛 (Bmal1hep-/-) 的小鼠.
- 分析了骨肌肉中的转录节奏.
- 用来自Bmal1hep-/-和野生型 (WT) 小鼠的血清治疗肌管.
主要成果:
- 肝脏时钟调节大约三分之一的骨肌肉转录节奏.
- 来自Bmal1hep-/-小鼠的血清抑制了代谢基因表达和线粒体ATP在髓管中的产生,特别是在活性阶段.
- 肝脏时钟对肌肉新陈代谢的影响主要是通过微调基因表达.
结论:
- 揭示了肝脏和骨肌肉钟之间的双向内分泌通信途径.
- 证明了肝脏时钟在调节肌肉代谢基因表达和功能的作用.
- 建议针对肝脏和肌肉的昼夜钟作为代谢疾病的潜在策略.
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