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

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 Kong; Cai Chen; Shu Zhang; Qilin Yu; Xuemei Fan; Shiwei Liu; Yanjun Liu; Cong Yi Wang

doi:10.1038/s41467-025-57444-y

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

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 Kong
, Cai Chen
, Shu Zhang
, Qilin Yu
, Xuemei Fan

Shiwei Liu^*, Yanjun Liu^*, Cong Yi Wang^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

10 Citations (Scopus)

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-kappa B 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.

Original language	English
Article number	2743
Number of pages	22
Journal	Nature Communications
Volume	16
Issue number	1
DOIs	https://doi.org/10.1038/s41467-025-57444-y
Publication status	Published - 20 Mar 2025
Externally published	Yes

Keywords

Alpha
Exosomes
Gene-expression
Inflammation
Insulin-resistance
Mirnas
Salsalate
T-cells
Tissue

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10.1038/s41467-025-57444-y

Cite this

Zhou, Q., Gao, J., Wu, G., Wang, C., Yang, Y., Huang, T., Wang, Y., Yue, T., Gao, Z., Xie, H., Xiong, F., Xiang, K., Yong, T., Zhang, W., Zhang, T., Kong, W., Chen, C., Zhang, S., Yu, Q., ... Wang, C. Y. (2025). Adipose progenitor cell-derived extracellular vesicles suppress macrophage M1 program to alleviate midlife obesity. Nature Communications, 16(1), Article 2743. https://doi.org/10.1038/s41467-025-57444-y

@article{117255d23ae445709b81f3325ade1458,

title = "Adipose progenitor cell-derived extracellular vesicles suppress macrophage M1 program to alleviate midlife obesity",

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-kappa B 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.",

keywords = "Alpha, Exosomes, Gene-expression, Inflammation, Insulin-resistance, Mirnas, Salsalate, T-cells, Tissue",

author = "Qing Zhou and Jia Gao and Guorao Wu and Chenwei Wang and Yan Yang and Teng Huang and Yi Wang and Tiantian Yue and Zhichao Gao and Hao Xie and Fei Xiong and Ke Xiang and Tuying Yong and Wanguang Zhang and Tongtong Zhang and Wen Kong and Cai Chen and Shu Zhang and Qilin Yu and Xuemei Fan and Shiwei Liu and Yanjun Liu and Wang, \{Cong Yi\}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025.",

year = "2025",

month = mar,

day = "20",

doi = "10.1038/s41467-025-57444-y",

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Zhou, Q, Gao, J, Wu, G, Wang, C, Yang, Y, Huang, T, Wang, Y, Yue, T, Gao, Z, Xie, H, Xiong, F, Xiang, K, Yong, T, Zhang, W, Zhang, T, Kong, W, Chen, C, Zhang, S, Yu, Q, Fan, X, Liu, S, Liu, Y & Wang, CY 2025, 'Adipose progenitor cell-derived extracellular vesicles suppress macrophage M1 program to alleviate midlife obesity', Nature Communications, vol. 16, no. 1, 2743. https://doi.org/10.1038/s41467-025-57444-y

TY - JOUR

T1 - Adipose progenitor cell-derived extracellular vesicles suppress macrophage M1 program to alleviate midlife obesity

AU - Zhou, Qing

AU - Gao, Jia

AU - Wu, Guorao

AU - Wang, Chenwei

AU - Yang, Yan

AU - Huang, Teng

AU - Wang, Yi

AU - Yue, Tiantian

AU - Gao, Zhichao

AU - Xie, Hao

AU - Xiong, Fei

AU - Xiang, Ke

AU - Yong, Tuying

AU - Zhang, Wanguang

AU - Zhang, Tongtong

AU - Kong, Wen

AU - Chen, Cai

AU - Zhang, Shu

AU - Yu, Qilin

AU - Fan, Xuemei

AU - Liu, Shiwei

AU - Liu, Yanjun

AU - Wang, Cong Yi

PY - 2025/3/20

Y1 - 2025/3/20

N2 - 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-kappa B 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.

AB - 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-kappa B 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.

KW - Alpha

KW - Exosomes

KW - Gene-expression

KW - Inflammation

KW - Insulin-resistance

KW - Mirnas

KW - Salsalate

KW - T-cells

KW - Tissue

UR - https://www.scopus.com/pages/publications/105000543769

U2 - 10.1038/s41467-025-57444-y

DO - 10.1038/s41467-025-57444-y

M3 - Article

C2 - 40113754

AN - SCOPUS:105000543769

SN - 2041-1723

VL - 16

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 2743

ER -

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

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Keywords

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