Distinct adipose progenitor cells emerging with age drive active adipogenesis

IF 44.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Pub Date : 2025-04-25 DOI:10.1126/science.adj0430

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

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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.

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不同的脂肪祖细胞随着年龄的增长而出现，驱动活跃的脂肪形成

从中年开始，成年人往往会出现内脏脂肪过多及相关的不良代谢紊乱。对小鼠的品系追踪发现，内脏脂肪中的脂肪祖细胞（APCs）在中年时期经历了广泛的脂肪生成过程。因此，尽管青壮年时期脂肪细胞的更替率很低，但脂肪生成在中年时期被释放出来。移植定量显示，中年小鼠的APC细胞自主表现出很高的脂肪生成能力。单细胞 RNA 测序发现，中年小鼠体内出现了一个独特的 APC 群体，即成熟的前脂肪细胞（CP-A）。CP-As 的增殖和脂肪生成活性都有所提高。药理和遗传操作表明，白血病抑制因子受体信号对于 CP-A 的脂肪生成和内脏脂肪扩张是不可或缺的。这些发现揭示了年龄依赖性脂肪重塑的基本机制，为研究与年龄相关的代谢性疾病提供了重要启示。

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来源期刊

Science 综合性期刊-综合性期刊

CiteScore

61.10

自引率

0.90%

发文量

审稿时长

2.1 months

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