妊娠和哺乳期肝细胞代谢适应，这一成果由北京大学徐成冉团队经过不懈努力而取得。该项研究成果发表在2025年8月28日出版的《细胞》上。
利用高分辨率单细胞RNA测序，该课题组研究人员系统地表征了小鼠在妊娠和产后阶段的肝细胞适应。研究团队发现了一种周期性的肝细胞轨迹（“妊娠时钟”），它控制着妊娠和产后恢复期间的代谢变化，在非哺乳期小鼠中恢复到妊娠前状态。哺乳诱导了明显的分支轨迹，其特征是脂质合成和输出升高。糖蛋白130 （gp130）的缺失破坏了妊娠期间肝脏的适应性，损害了胎儿的生长，而产后乙酰辅酶A （CoA）合成酶2 （ACSS2）缺乏则损害了肝脏脂质的生物合成和输出，降低了牛奶中的脂质含量，影响了后代的发育。与绵羊的比较分析强调了尽管物种之间存在遗传差异，但保守的肝脏代谢适应途径。这些见解阐明了妊娠和哺乳期间肝细胞的可塑性，确定了优化母胎健康和哺乳性能的潜在治疗靶点，对生殖生物学和牲畜管理具有重要意义。
据介绍，肝脏在妊娠期和哺乳期经历代谢适应以满足不断变化的生理需求，但其确切的过程、调节机制和功能尚不清楚。
附：英文原文
Title: Hepatocyte metabolic adaptations during pregnancy and lactation
Author: Li Yang, Yu Zhang, Xin-Xin Yu, Yu-Heng Zhou, Shuang He, Liu Yang, Tong-Yun Mao, Jun-Ge Yang, Ying Wu, Qi-Qi Zheng, Xun-Kai Li, Hou-Zao Chen, Cheng-Ran Xu
Issue&Volume: 2025-08-28
Abstract: The liver undergoes metabolic adaptations during gestation and lactation to meet evolving physiological demands, yet the precise processes, regulatory mechanisms, and functions remain unclear. Using high-resolution single-cell RNA sequencing, we systematically characterized hepatocyte adaptations in mice across pregnancy and postpartum stages. We discovered a cyclical hepatocyte trajectory (“pregnancy clock”) that governs metabolic changes during gestation and postpartum recovery, reverting to pregestational states in non-lactating mice. Lactation induced a distinct branching trajectory characterized by elevated lipid synthesis and export. Deletion of glycoprotein 130 (gp130) disrupted hepatic adaptations during pregnancy, impairing fetal growth, whereas acetyl-coenzyme A (CoA) synthetase 2 (ACSS2) deficiency postpartum impaired hepatic lipid biosynthesis and export, reducing milk lipid content and compromising offspring development. Comparative analysis with sheep highlighted conserved hepatic metabolic adaptation pathways despite genetic divergence between species. These insights clarify hepatocyte plasticity during pregnancy and lactation, identifying potential therapeutic targets to optimize maternal-fetal health and lactation performance, with implications for reproductive biology and livestock management.
DOI: 10.1016/j.cell.2025.08.007
Source: https://www.cell.com/cell/abstract/S0092-8674(25)00921-3