Distinct adipose progenitor cells emerging with age drive active adipogenesis

• 成果类型: Article
• 署名作者: Wang, Guan; Li, Gaoyan; Song, Anying; Zhao, Yutian; Yu, Jiayu; Wang, Yifan; Dai, Wenting; Salas, Martha; Qin, Hanjun; Medrano, Leonard; Dow, Joan; Li, Aimin; Armstrong, Brian; Fueger, Patrick T.; Yu, Hua; Zhu, Yi; Shao, Mengle; Wu, Xiwei; Jiang, Lei; Campisi, Judith; Yang, Xia; Wang, Qiong A.
• 署名单位: City of Hope; University of California System; University of California Los Angeles; City of Hope; City of Hope; City of Hope; City of Hope; City of Hope; City of Hope; Beckman Research Institute of City of Hope; Baylor College of Medicine; Chinese Academy of Sciences; Shanghai Institute of Immunity and Infection, CAS; Buck Institute for Research on Aging; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8290
• DOI: 10.1126/science.adj0430
• 发表日期: 2025-04-25
• 关键词: cellular senescence; tissue; fat; obesity; diet; stem; mechanisms; adipocytes; damage; HEALTH

摘要

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.