Adipose progenitor cell-derived extracellular vesicles suppress macrophage M1 program to alleviate midlife obesity
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.
Authors
- Cong‐Yi Wang (ORCID: https://orcid.org/0000-0001-7914-168X)
- Tuying Yong (ORCID: https://orcid.org/0000-0002-1255-9798)
- Wanguang Zhang (ORCID: https://orcid.org/0000-0003-3184-9907)
- Tiantian Yue (ORCID: https://orcid.org/0000-0003-0307-207X)
- Zhichao Gao
- Hao Xie (ORCID: https://orcid.org/0000-0002-9640-4055)
- Ke Xiang (ORCID: https://orcid.org/0000-0001-7439-2076)
- Teng Huang
- Guorao Wu
- Xuemei Fan
- Qing Zhou (ORCID: https://orcid.org/0000-0003-4508-9224)
- Jia Gao (ORCID: https://orcid.org/0000-0001-5335-1523)
- Fei Xiong (ORCID: https://orcid.org/0000-0002-4280-5734)
- Cai Chen (ORCID: https://orcid.org/0000-0002-7596-6307)
- Yi Wang (ORCID: https://orcid.org/0000-0002-2109-2157)
- Shiwei Liu (ORCID: https://orcid.org/0000-0003-3918-951X)
- Shu Zhang (ORCID: https://orcid.org/0000-0002-8521-7916)
- Yanjun Liu (ORCID: https://orcid.org/0000-0002-0627-928X)
- Chenwei Wang (ORCID: https://orcid.org/0000-0002-0920-8639)
- Tongtong Zhang (ORCID: https://orcid.org/0000-0003-4786-5776)
- Qilin Yu
- Wen Kong (ORCID: https://orcid.org/0000-0002-9275-8809)
- Ying Yang (ORCID: https://orcid.org/0009-0006-8248-2358)
Institutions
- Union Hospital (HK)
- Shanxi Medical University (CN)
- Baylor College of Medicine (US)
- Third People's Hospital of Chengdu (CN)
- Central Hospital of Wuhan (CN)
- Shanxi Academy of Medical Sciences (CN)
- Tongji Hospital (CN)
- Huazhong University of Science and Technology (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-03-20
- DOI
- https://doi.org/10.1038/s41467-025-57444-y
- Citations
- 14
- Primary Topic
- Extracellular vesicles in disease
- Type
- article
- Field-Weighted Citation Impact
- 11.28
Funders
- National Natural Science Foundation of China
- China International Medical Foundation
- National Key Research and Development Program of China