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  3. Adipose progenitor cell-derived extracellular vesicles suppress macrophage M1 program to alleviate midlife obesity

Adipose progenitor cell-derived extracellular vesicles suppress macrophage M1 program to alleviate midlife obesity

  • Nat Commun. 2025 Mar 20;16(1):2743. doi: 10.1038/s41467-025-57444-y.
Qing Zhou # 1,  Jia Gao # 1,  Guorao Wu # 1,  Chenwei Wang # 2,  Yan Yang 3,  Teng Huang 4,  Yi Wang 1,  Tiantian Yue 1,  Zhichao Gao 1,  Hao Xie 1,  Fei Xiong 1,  Ke Xiang 1,  Tuying Yong 5,  Wanguang Zhang 6,  Tongtong Zhang 7,  Wen Kong 8,  Cai Chen 9,  Shu Zhang 1,  Qilin Yu 1,  Xuemei Fan 10,  Shiwei Liu 11,  Yanjun Liu 12,  Cong-Yi Wang 13 14
Affiliations

Affiliations

  • 1 Department of Respiratory and Critical Care Medicine, the Center for Biomedical Research, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 2 Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, 77030, USA.
  • 3 Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 4 Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 5 National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
  • 6 Department of Hepatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 7 Center of Gastrointestinal and Minimally Invasive Surgery, Department of General Surgery, The Third People's Hospital of Chengdu, Chengdu, China.
  • 8 Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 9 Department of Endocrinology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 10 Shanxi Bethune Hospital, Shanxi Academy of Medical Science, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, the Key Laboratory of Endocrine and Metabolic Diseases of Shanxi Province, Taiyuan, China.
  • 11 Shanxi Bethune Hospital, Shanxi Academy of Medical Science, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, the Key Laboratory of Endocrine and Metabolic Diseases of Shanxi Province, Taiyuan, China. lswspring6@aliyun.com.
  • 12 Center of Gastrointestinal and Minimally Invasive Surgery, Department of General Surgery, The Third People's Hospital of Chengdu, Chengdu, China. liuyanjun_001@163.com.
  • 13 Shanxi Bethune Hospital, Shanxi Academy of Medical Science, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, the Key Laboratory of Endocrine and Metabolic Diseases of Shanxi Province, Taiyuan, China. wangcy@tjh.tjmu.edu.cn.
  • 14 The Center for Biomedical Research, Tongji Hospital Research Building, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, China. wangcy@tjh.tjmu.edu.cn.
  • # Contributed equally.
PMID: 40113754 DOI: 10.1038/s41467-025-57444-y
Abstract

Among different age groups, middle-aged individuals are particularly susceptible to obesity, with a 22% higher risk of all-cause mortality. However, the underlying mechanisms remain unclear. In this study, we identify adipose progenitor cells (APCs) in the white adipose tissue (WAT) of middle-aged subjects as potential causes of midlife obesity. Specifically, the extracellular vesicles (EVs) derived from APCs display an impaired ability to mitigate the inflammaging of adipose tissue macrophages (ATMs) in middle-aged individuals. Mechanistically, these EVs, lacking miR-145-5p, fail to suppress the expression of L-selectin in ATMs, thereby facilitating their M1 program via the NF-κB signaling pathway. In contrast, EVs from young APCs effectively inhibit M1 macrophage polarization. Accordingly, targeted liposomes are designed to deliver miR-145-5p mimics to ATMs, which effectively prevent the obesity in middle-aged mice. Collectively, our findings highlight the role of APC-derived EVs in midlife obesity and propose miR-145-5pas a promising therapeutic target for clinical applications.

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