CD47-blocking antibody confers metabolic benefits against obesity
CD47-blocking antibody is a well-known potential antibody drug for tumor immunotherapy. However, it is unclear whether CD47-blocking antibody can protect against metabolic disorders. We report that high-fat diet (HFD)-induced obesity increases CD47 expression, while exercise downregulates it in skeletal muscle. Administration of CD47-blocking antibody in mice prevents HFD-induced weight gain and glucose intolerance, enhances exercise capacity, and improves body composition and skeletal muscle mitochondrial function. Mechanistically, the protective effects conferred by CD47-blocking antibody are mediated through activation of AMP-activated protein kinase (AMPK) in skeletal muscle. Consistently, muscle-specific CD47-knockout mice show similar metabolic improvements, indicating a direct muscle-specific role of CD47 in regulating AMPK activation in vivo. Furthermore, the CD47-blocking antibody reduces the phosphorylation of heat shock protein 90α (HSP90α) to activate AMPK in skeletal muscle. In conclusion, CD47-blocking antibody confers metabolic benefits by activating the AMPK pathway in skeletal muscle.
Authors
- Kaijiang Yang (ORCID: https://orcid.org/0009-0008-7414-9285)
- Yu Dong (ORCID: https://orcid.org/0000-0002-3634-3318)
- Duran Qin
- Zhen‐Ning Zhang (ORCID: https://orcid.org/0000-0003-3798-7104)
- Gaowei Wang
- Yunhui Kong (ORCID: https://orcid.org/0000-0003-3004-7574)
- Weida Li (ORCID: https://orcid.org/0000-0001-6578-6321)
- Jingzhi Zhang (ORCID: https://orcid.org/0000-0001-5672-8349)
- Qiaolin Deng (ORCID: https://orcid.org/0000-0001-6378-3872)
- Feifei Huang (ORCID: https://orcid.org/0000-0002-7496-4908)
- Mengting Gong
- Qing He (ORCID: https://orcid.org/0000-0002-3588-9466)
- Zian Chen (ORCID: https://orcid.org/0000-0002-7662-8713)
- Zhejin Sheng
- Y. J. Su
- Shaorong Gao
- Xiaobo Li (ORCID: https://orcid.org/0000-0002-3881-7468)
- Hong Wang (ORCID: https://orcid.org/0000-0003-2289-8862)
- Pei Yu (ORCID: https://orcid.org/0000-0002-8848-0584)
- Minglu Xu
- Jingyu Sun
- Ping Hu (ORCID: https://orcid.org/0000-0001-8832-1391)
- Xiangyi Chen (ORCID: https://orcid.org/0000-0003-1804-6755)
- Zhaoyue Wang (ORCID: https://orcid.org/0000-0002-5820-8416)
- R. Le
Institutions
- Tongji University (CN)
- Karolinska Institutet (SE)
- Nanjing University (CN)
Publication Details
- Journal
- Cell Reports Medicine
- Published
- 2025-04-22
- DOI
- https://doi.org/10.1016/j.xcrm.2025.102089
- Citations
- 3
- Primary Topic
- Phagocytosis and Immune Regulation
- Type
- article
- Field-Weighted Citation Impact
- 2.39