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 midd...
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Nature Portfolio
2025-03-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-57444-y |
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| author | 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 |
| author_facet | 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 |
| author_sort | Qing Zhou |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-101cbe350bc1443ea69f5f5108e4eaf7 |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-101cbe350bc1443ea69f5f5108e4eaf72025-08-20T02:41:32ZengNature PortfolioNature Communications2041-17232025-03-0116112210.1038/s41467-025-57444-yAdipose progenitor cell-derived extracellular vesicles suppress macrophage M1 program to alleviate midlife obesityQing Zhou0Jia Gao1Guorao Wu2Chenwei Wang3Yan Yang4Teng Huang5Yi Wang6Tiantian Yue7Zhichao Gao8Hao Xie9Fei Xiong10Ke Xiang11Tuying Yong12Wanguang Zhang13Tongtong Zhang14Wen Kong15Cai Chen16Shu Zhang17Qilin Yu18Xuemei Fan19Shiwei Liu20Yanjun Liu21Cong-Yi Wang22Department 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 TechnologyDepartment 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 TechnologyDepartment 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 TechnologyLester and Sue Smith Breast Center, Baylor College of MedicineDepartment of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment 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 TechnologyDepartment 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 TechnologyDepartment 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 TechnologyDepartment 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 TechnologyDepartment 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 TechnologyDepartment 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 TechnologyNational Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and TechnologyDepartment of Hepatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyCenter of Gastrointestinal and Minimally Invasive Surgery, Department of General Surgery, The Third People’s Hospital of ChengduDepartment of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Endocrinology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and TechnologyDepartment 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 TechnologyDepartment 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 TechnologyShanxi 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 ProvinceShanxi 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 ProvinceCenter of Gastrointestinal and Minimally Invasive Surgery, Department of General Surgery, The Third People’s Hospital of ChengduShanxi 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 ProvinceAbstract 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.https://doi.org/10.1038/s41467-025-57444-y |
| spellingShingle | 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 Adipose progenitor cell-derived extracellular vesicles suppress macrophage M1 program to alleviate midlife obesity Nature Communications |
| title | Adipose progenitor cell-derived extracellular vesicles suppress macrophage M1 program to alleviate midlife obesity |
| title_full | Adipose progenitor cell-derived extracellular vesicles suppress macrophage M1 program to alleviate midlife obesity |
| title_fullStr | Adipose progenitor cell-derived extracellular vesicles suppress macrophage M1 program to alleviate midlife obesity |
| title_full_unstemmed | Adipose progenitor cell-derived extracellular vesicles suppress macrophage M1 program to alleviate midlife obesity |
| title_short | Adipose progenitor cell-derived extracellular vesicles suppress macrophage M1 program to alleviate midlife obesity |
| title_sort | adipose progenitor cell derived extracellular vesicles suppress macrophage m1 program to alleviate midlife obesity |
| url | https://doi.org/10.1038/s41467-025-57444-y |
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