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

Author

Listed:
  • Qing Zhou

    (Huazhong University of Science and Technology)

  • Jia Gao

    (Huazhong University of Science and Technology)

  • Guorao Wu

    (Huazhong University of Science and Technology)

  • Chenwei Wang

    (Baylor College of Medicine)

  • Yan Yang

    (Huazhong University of Science and Technology)

  • Teng Huang

    (Huazhong University of Science and Technology)

  • Yi Wang

    (Huazhong University of Science and Technology)

  • Tiantian Yue

    (Huazhong University of Science and Technology)

  • Zhichao Gao

    (Huazhong University of Science and Technology)

  • Hao Xie

    (Huazhong University of Science and Technology)

  • Fei Xiong

    (Huazhong University of Science and Technology)

  • Ke Xiang

    (Huazhong University of Science and Technology)

  • Tuying Yong

    (Huazhong University of Science and Technology)

  • Wanguang Zhang

    (Huazhong University of Science and Technology)

  • Tongtong Zhang

    (The Third People’s Hospital of Chengdu)

  • Wen Kong

    (Huazhong University of Science and Technology)

  • Cai Chen

    (Huazhong University of Science and Technology)

  • Shu Zhang

    (Huazhong University of Science and Technology)

  • Qilin Yu

    (Huazhong University of Science and Technology)

  • Xuemei Fan

    (the Key Laboratory of Endocrine and Metabolic Diseases of Shanxi Province)

  • Shiwei Liu

    (the Key Laboratory of Endocrine and Metabolic Diseases of Shanxi Province)

  • Yanjun Liu

    (The Third People’s Hospital of Chengdu)

  • Cong-Yi Wang

    (the Key Laboratory of Endocrine and Metabolic Diseases of Shanxi Province
    Huazhong University of Sciences and Technology)

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.

Suggested Citation

  • Qing Zhou & Jia Gao & Guorao Wu & Chenwei Wang & Yan Yang & Teng Huang & Yi Wang & Tiantian Yue & Zhichao Gao & Hao Xie & Fei Xiong & Ke Xiang & Tuying Yong & Wanguang Zhang & Tongtong Zhang & Wen Kon, 2025. "Adipose progenitor cell-derived extracellular vesicles suppress macrophage M1 program to alleviate midlife obesity," Nature Communications, Nature, vol. 16(1), pages 1-22, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57444-y
    DOI: 10.1038/s41467-025-57444-y
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