英国伦敦帝国理工学院William R. Scott.小组的研究开发出了肥胖和减肥中脂肪生态位的选择性重构。相关论文发表在2025年7月9日出版的《自然》杂志上。

在这里，该研究团队报告了一个空间分辨率的单核图谱（包括来自70人的171247个细胞），研究了肥胖和治疗性减肥中重塑人类AT的细胞类型、分子事件和调节因素，以及它们的代谢健康。课题组人员发现代谢细胞、前体细胞和血管细胞对衰老的选择性脆弱性，并揭示衰老可以通过减肥有效地逆转。课题组研究人员定义基因调控机制和组织信号，可能驱动退化周期的衰老，组织损伤和代谢功能障碍。

该课题组人员发现体重减轻减少脂肪细胞肥大和生物力学约束途径，激活全球代谢通量和生物能量底物循环，可能介导代谢健康的系统性改善。在免疫区，研究团队证明了减肥抑制肥胖诱导的巨噬细胞浸润，但不能完全逆转激活，使这些细胞准备触发潜在的体重恢复和恶化代谢功能障碍。在整个过程中，该课题组研究人员将细胞映射到组织壁龛，以了解组织损伤和恢复的集体决定因素。总的来说，他们互补的单核和空间数据集为肥胖AT功能障碍的基础及其通过减肥逆转提供了前所未有的见解，并且是机制和治疗探索的关键阻力。

据了解，减肥可显著改善肥胖人群的代谢和心血管健康。脂肪组织（AT）的重塑是这些多样而重要的临床效果的核心。然而，令人惊讶的是，人们对其潜在机制知之甚少，这对治疗进展构成了障碍。

附：英文原文

Title: Selective remodelling of the adipose niche in obesity and weight loss

Author: Miranda, Antonio M. A., McAllan, Liam, Mazzei, Guianfranco, Andrew, Ivan, Davies, Iona, Ertugrul, Meryem, Kenkre, Julia, Kudo, Hiromi, Carrelha, Joana, Patel, Bhavik, Newton, Sophie, Zhang, Weihua, Pollard, Alice, Cross, Amy, McCallion, Oliver, Jang, Mikyung, Choi, Ka Lok, Brown, Scarlett, Rasool, Yasmin, Adamo, Marco, Elkalaawy, Mohamed, Jenkinson, Andrew, Mohammadi, Borzoueh, Hashemi, Majid, Goldin, Robert, Game, Laurence, Hester, Joanna, Issa, Fadi, Ryan, Dylan G., Ortega, Patricia, Ahmed, Ahmed R., Batterham, Rachel L., Chambers, John C., Kooner, Jaspal S., Baranasic, Damir, Noseda, Michela, Tan, Tricia, Scott, William R.

Issue&Volume: 2025-07-09

Abstract: Weight loss significantly improves metabolic and cardiovascular health in people with obesity1,2,3. The remodelling of adipose tissue (AT) is central to these varied and important clinical effects4. However, surprisingly little is known about the underlying mechanisms, presenting a barrier to treatment advances. Here we report a spatially resolved single-nucleus atlas (comprising 171,247 cells from 70 people) investigating the cell types, molecular events and regulatory factors that reshape human AT, and thus metabolic health, in obesity and therapeutic weight loss. We discover selective vulnerability to senescence in metabolic, precursor and vascular cells and reveal that senescence is potently reversed by weight loss. We define gene regulatory mechanisms and tissue signals that may drive a degenerative cycle of senescence, tissue injury and metabolic dysfunction. We find that weight loss reduces adipocyte hypertrophy and biomechanical constraint pathways, activating global metabolic flux and bioenergetic substrate cycles that may mediate systemic improvements in metabolic health. In the immune compartment, we demonstrate that weight loss represses obesity-induced macrophage infiltration but does not completely reverse activation, leaving these cells primed to trigger potential weight regain and worsen metabolic dysfunction. Throughout, we map cells to tissue niches to understand the collective determinants of tissue injury and recovery. Overall, our complementary single-nucleus and spatial datasets offer unprecedented insights into the basis of obese AT dysfunction and its reversal by weight loss and are a key resource for mechanistic and therapeutic exploration.

DOI: 10.1038/s41586-025-09233-2

Source: https://www.nature.com/articles/s41586-025-09233-2