| First Author | Imada S | Year | 2024 |
| Journal | Nature | Volume | 633 |
| Issue | 8031 | Pages | 895-904 |
| PubMed ID | 39169180 | Mgi Jnum | J:359275 |
| Mgi Id | MGI:7785606 | Doi | 10.1038/s41586-024-07840-z |
| Citation | Imada S, et al. (2024) Short-term post-fast refeeding enhances intestinal stemness via polyamines. Nature 633(8031):895-904 |
| abstractText | For over a century, fasting regimens have improved health, lifespan and tissue regeneration in diverse organisms, including humans(1-6). 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. |
