从中年开始，成年人经常患有内脏肥胖和相关的不良代谢紊乱。小鼠的谱系追踪显示，内脏脂肪中的脂肪祖细胞（APCs）在中年时经历了广泛的脂肪形成。尽管年轻成人的脂肪细胞周转率较低，但在中年时期，脂肪形成被解除。定量移植表明，中年小鼠APC具有较高的细胞自主成脂能力。单细胞RNA测序确定了一个独特的APC群体，即在这个年龄段出现的承诺前脂肪细胞，年龄富集（CP-A）。CP-A显示增殖和脂肪形成活性升高。药理学和遗传学操作表明，白血病抑制因子受体信号是不可或缺的CP-A脂肪形成和内脏脂肪扩张。这些发现揭示了年龄依赖性脂肪重塑的基本机制，为与年龄相关的代谢疾病提供了重要的见解。
附：英文原文
Title: Distinct adipose progenitor cells emerging with age drive active adipogenesis
Author: Guan Wang, Gaoyan Li, Anying Song, Yutian Zhao, Jiayu Yu, Yifan Wang, Wenting Dai, Martha Salas, Hanjun Qin, Leonard Medrano, Joan Dow, Aimin Li, Brian Armstrong, Patrick T. Fueger, Hua Yu, Yi Zhu, Mengle Shao, Xiwei Wu, Lei Jiang, Judith Campisi, Xia Yang, Qiong A. Wang
Issue&Volume: 2025-04-25
Abstract: Starting at middle age, adults often suffer from visceral adiposity and associated adverse metabolic disorders. Lineage tracing in mice revealed that adipose progenitor cells (APCs) in visceral fat undergo extensive adipogenesis during middle age. Thus, despite the low turnover rate of adipocytes in young adults, adipogenesis is unlocked during middle age. Transplantations quantitatively showed that APCs in middle-aged mice exhibited high adipogenic capacity cell-autonomously. Single-cell RNA sequencing identified a distinct APC population, the committed preadipocyte, age-enriched (CP-A), emerging at this age. CP-As demonstrated elevated proliferation and adipogenesis activity. Pharmacological and genetic manipulations indicated that leukemia inhibitory factor receptor signaling was indispensable for CP-A adipogenesis and visceral fat expansion. These findings uncover a fundamental mechanism of age-dependent adipose remodeling, offering critical insights into age-related metabolic diseases.
DOI: adj0430
Source: https://www.science.org/doi/10.1126/science.adj0430