密歇根大学Daniel R. Wahl团队的一项最新研究提出了皮质糖代谢的重新布线促进了人类脑癌的生长。相关论文于2025年9月3日发表在《自然》杂志上。

在这里，该课题组人员将13c标记的葡萄糖注入患有脑癌的患者和小鼠中，结合定量代谢通量分析，绘制肿瘤与大脑皮层中葡萄糖衍生碳的命运。通过直接和全面测量皮层和胶质瘤组织中的碳和氮标记，课题组人员确定了深刻的代谢转化。在人体皮层中，葡萄糖碳为必要的生理过程提供燃料，包括三羧酸循环氧化和神经递质合成。

相反，胶质瘤下调这些过程，并从环境中清除氨基酸等替代碳强度，重新利用葡萄糖衍生的碳来产生增殖和侵袭所需的分子。通过膳食氨基酸调节靶向小鼠的这种代谢重组，选择性地改变胶质母细胞瘤的代谢，减缓肿瘤的生长，并增强标准治疗的疗效。这些发现阐明了侵袭性脑肿瘤是如何利用葡萄糖抑制正常生理活动以促进恶性扩张的，并为提高治疗效果提供了潜在的治疗策略。

据了解，大脑大量消耗葡萄糖，为神经生理提供能量。脑癌，如胶质母细胞瘤，放弃了生理完整性，获得了增殖和侵入健康组织的能力。脑癌如何重新连接葡萄糖主题以驱动侵略性生长尚不清楚。

附：英文原文

Title: Rewiring of cortical glucose metabolism fuels human brain cancer growth

Author: Scott, Andrew J., Mittal, Anjali, Meghdadi, Baharan, OBrien, Alexandra, Bailleul, Justine, Sravya, Palavalasa, Achreja, Abhinav, Zhou, Weihua, Xu, Jie, Lin, Angelica, Wilder-Romans, Kari, Liang, Ningning, Kothari, Ayesha U., Korimerla, Navyateja, Edwards, Donna M., Wu, Zhe, Feng, Jiane, Su, Sophia, Zhang, Li, Sajjakulnukit, Peter, Andren, Anthony C., Park, Junyoung O., ten Hoeve, Johanna, Tarnal, Vijay, Redic, Kimberly A., Qi, Nathan R., Fischer, Joshua L., Yang, Ethan, Regan, Michael S., Stopka, Sylwia A., Baquer, Gerard, Suresh, Krithika, Sarkaria, Jann N., Lawrence, Theodore S., Venneti, Sriram, Agar, Nathalie Y. R., Vlashi, Erina, Lyssiotis, Costas A., Al-Holou, Wajd N., Nagrath, Deepak, Wahl, Daniel R.

Issue&Volume: 2025-09-03

Abstract: The brain avidly consumes glucose to fuel neurophysiology1. Cancers of the brain, such as glioblastoma, relinquish physiological integrity and gain the ability to proliferate and invade healthy tissue2. How brain cancers rewire glucose use to drive aggressive growth remains unclear. Here we infused 13C-labelled glucose into patients and mice with brain cancer, coupled with quantitative metabolic flux analysis, to map the fates of glucose-derived carbon in tumour versus cortex. Through direct and comprehensive measurements of carbon and nitrogen labelling in both cortex and glioma tissues, we identify profound metabolic transformations. In the human cortex, glucose carbons fuel essential physiological processes, including tricarboxylic acid cycle oxidation and neurotransmitter synthesis. Conversely, gliomas downregulate these processes and scavenge alternative carbon sources such as amino acids from the environment, repurposing glucose-derived carbons to generate molecules needed for proliferation and invasion. Targeting this metabolic rewiring in mice through dietary amino acid modulation selectively alters glioblastoma metabolism, slows tumour growth and augments the efficacy of standard-of-care treatments. These findings illuminate how aggressive brain tumours exploit glucose to suppress normal physiological activity in favour of malignant expansion and offer potential therapeutic strategies to enhance treatment outcomes.

DOI: 10.1038/s41586-025-09460-7

Source: https://www.nature.com/articles/s41586-025-09460-7