This study investigates the role of Annexin A1 (ANXA1) in obesity and its underlying mechanisms. Elevated ANXA1 levels were found in obese individuals' adipose tissue. ANXA1 deletion worsened obesity and metabolic disorders in mice, while ANXA1 overexpression had the opposite effect. Mechanistically, ANXA1 competes with MYCBP2 for PDLIM7 binding, promoting SMAD4 ubiquitination and degradation, thus downregulating PPARγ and reducing adipogenesis. Ac2-26, an ANXA1-derived peptide, also inhibited adipogenesis and obesity. This research identifies ANXA1 as a potential target for obesity prevention and treatment.

Lu Fang, Changjie Liu, Zong-zhe Jiang, Mengxiao Wang, Kang Geng, Yangkai Xu, Yujie Zhu, Yiwen Fu, Jing Xue, Wenxin Shan, Qi Zhang, Jie Chen, Jiahong Chen, Mingming Zhao, Yuxuan Guo, K. W. Michael Siu, Y. Eugene Chen, Yong Xu, Donghui Liu, Lemin Zheng