德国马克斯·普朗克分子遗传学研究所Aydan Bulut-Karslioglu团队近期取得重要工作进展，他们研究提出，FOXO1介导的脂质代谢维持哺乳动物胚胎休眠。相关研究成果2024年1月4日在线发表于《自然—细胞生物学》杂志上。

据介绍，哺乳动物的发育时间可以在体内通过将着床前的胚胎保存在称为滞育的休眠状态来调节。生长抑制调节剂mTOR（mTORi）会暂停小鼠在体外的发育，但胚胎休眠是如何维持的尚不清楚。

研究人员展示了滞育中的小鼠胚胎是通过使用脂质作为主要能源来维持的。在体外，向胚胎补充代谢产物L-肉碱可以平衡脂质消耗，使胚胎处于更深的休眠状态，并延长胚胎寿命。研究人员确定FOXO1是休眠胚胎能量平衡的重要调节因子，并通过对休眠细胞特征的荟萃分析提出，它可能是成年组织休眠的常见调节因子。

总之，这一研究结果解除了体外胚胎存活的限制，并表明脂质代谢可能是与寿命和跨组织干细胞功能相关的关键代谢转变。

附：英文原文

Title: FOXO1-mediated lipid metabolism maintains mammalian embryos in dormancy

Author: van der Weijden, Vera A., Sttzel, Maximilian, Iyer, Dhanur P., Fauler, Beatrix, Gralinska, Elzbieta, Shahraz, Mohammed, Meierhofer, David, Vingron, Martin, Rulands, Steffen, Alexandrov, Theodore, Mielke, Thorsten, Bulut-Karslioglu, Aydan

Issue&Volume: 2024-01-04

Abstract: Mammalian developmental timing is adjustable in vivo by preserving pre-implantation embryos in a dormant state called diapause. Inhibition of the growth regulator mTOR (mTORi) pauses mouse development in vitro, yet how embryonic dormancy is maintained is not known. Here we show that mouse embryos in diapause are sustained by using lipids as primary energy source. In vitro, supplementation of embryos with the metabolite L-carnitine balances lipid consumption, puts the embryos in deeper dormancy and boosts embryo longevity. We identify FOXO1 as an essential regulator of the energy balance in dormant embryos and propose, through meta-analyses of dormant cell signatures, that it may be a common regulator of dormancy across adult tissues. Our results lift a constraint on in vitro embryo survival and suggest that lipid metabolism may be a critical metabolic transition relevant for longevity and stem cell function across tissues.

DOI: 10.1038/s41556-023-01325-3

Source: https://www.nature.com/articles/s41556-023-01325-3