美国麻省理工学院Ömer H. Yilmaz和德国埃森大学医院和德国癌症协会Alpaslan Tasdogan共同合作，近期取得重要工作进展。他们研究提出，短期禁食后再进食可通过多胺增强肠道干性。相关研究成果2024年8月21日在线发表于《自然》杂志上。

据介绍，一个多世纪以来，禁食方案改善了包括人类在内的各种生物体的健康、寿命和组织再生。然而，禁食和禁食后再进食对成体干细胞和肿瘤形成的影响尚未得到深入探讨。

研究人员表明，禁食后进食会增加肠干细胞（ISC）增殖和肿瘤形成；禁食后进食会增强Lgr5⁺ ISC的再生能力，禁食后进食的ISC中肿瘤抑制基因Apc的缺失，会导致小肠和结肠的肿瘤发病率高于禁食或自由进食状态，这表明禁食后进食是一种独特的状态。从机制上讲，研究人员发现，快餐后ISC中强烈的mTORC1诱导通过多胺代谢增加蛋白质合成，从而推动这些变化，因为抑制mTORC1、多胺代谢物产生或蛋白质合成会消除快餐后的再生或致瘤效应。

总之，这一研究结果表明，在不增加癌症风险的情况下，在规划基于营养的再生策略时，必须仔细考虑和测试快速进食周期，因为快速进食会导致干细胞驱动的再生和致瘤性的爆发。

附：英文原文

Title: Short-term post-fast refeeding enhances intestinal stemness via polyamines

Author: Imada, Shinya, Khawaled, Saleh, Shin, Heaji, Meckelmann, Sven W., Whittaker, Charles A., Corra, Renan Oliveira, Alquati, Chiara, Lu, Yixin, Tie, Guodong, Pradhan, Dikshant, Calibasi-Kocal, Gizem, Nascentes Melo, Luiza Martins, Allies, Gabriele, Rsler, Jonas, Wittenhofer, Pia, Krystkiewicz, Jonathan, Schmitz, Oliver J., Roper, Jatin, Vinolo, Marco Aurelio Ramirez, Ricciardiello, Luigi, Lien, Evan C., Vander Heiden, Matthew G., Shivdasani, Ramesh A., Cheng, Chia-Wei, Tasdogan, Alpaslan, Yilmaz, mer H.

Issue&Volume: 2024-08-21

Abstract: For over a century, fasting regimens have improved health, lifespan and tissue regeneration in diverse organisms, including humans1,2,3,4,5,6. However, how fasting and post-fast refeeding affect adult stem cells and tumour formation has yet to be explored in depth. Here we demonstrate that post-fast refeeding increases intestinal stem cell (ISC) proliferation and tumour formation; post-fast refeeding augments the regenerative capacity of Lgr5+ ISCs, and loss of the tumour suppressor gene Apc in post-fast-refed ISCs leads to a higher tumour incidence in the small intestine and colon than in the fasted or ad libitum-fed states, demonstrating that post-fast refeeding is a distinct state. Mechanistically, we discovered that robust mTORC1 induction in post-fast-refed ISCs increases protein synthesis via polyamine metabolism to drive these changes, as inhibition of mTORC1, polyamine metabolite production or protein synthesis abrogates the regenerative or tumorigenic effects of post-fast refeeding. Given our findings, fast–refeeding cycles must be carefully considered and tested when planning diet-based strategies for regeneration without increasing cancer risk, as post-fast refeeding leads to a burst in stem-cell-driven regeneration and tumorigenicity.

DOI: 10.1038/s41586-024-07840-z

Source: https://www.nature.com/articles/s41586-024-07840-z