肝脏和小肠中的空间代谢梯度
Laith Z Samarah1,2,3, Clover Zheng4, Xi Xing1,2,3
1Department of Chemistry, Princeton University, Princeton, NJ, USA.
Nature
|October 15, 2025
概括
这项研究使用先进的成像和人工智能绘制了小鼠肝脏和肠道的空间代谢. 关键代谢物和能量压力标志物显示器官特定位置,揭示饮食如何影响代谢健康.
科学领域:
- 代谢学
- 系统生物学
- 器官生理学
背景情况:
- 细胞的功能和特性受其在器官内的空间位置的影响.
- 肝脏和肠道中的基因表达模式在空间上有所不同,这表明了潜在的代谢差异.
- 组织内空间代谢的直接评估是有限的,阻碍了对组织的充分理解.
研究的目的:
- 在小鼠肝脏和肠道中绘制空间代谢梯度.
- 研究饮食中的果糖在这些器官中的代谢命运.
- 了解空间代谢对器官功能和疾病的影响.
主要方法:
- 开发一个集成的实验计算工作流程.
- 使用矩阵辅助激光脱离/电离 (MALDI) 成像质谱法 (IMS).
- 结合同位素追踪和深度学习的人工智能进行代谢分析.
主要成果:
- 超过90%的测量代谢物在肝脏和肠道中表现出显著的空间度梯度.
- 三碳酸 (TCA) 循环代谢物和同位素标记局部化到肝脏 (外门) 和肠道 (尖端与密室) 的特定区域.
- 果糖的消耗导致肝脏中ATP的消耗,并改变了肠道的代谢.
结论:
- 建立了肝脏和肠道代谢组织的基础知识.
- 在肝脏代谢中发现果糖诱导的焦点乱.
- 突出了空间代谢在器官生理学和对饮食因素的反应中的关键作用.
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