GDF11 inhibits adipogenesis of human adipose-derived stromal cells through ALK5/KLF15/β-catenin/PPARγ cascade
Shimin Lin,
Lishan Zhong,
Jingyi Chen,
Zibo Zhao,
Rongze Wang,
Yexuan Zhu,
Junwei Liu,
Yanting Wu,
Cuifang Ye,
Fujun Jin,
Zhe Ren
Affiliations
Shimin Lin
Guangzhou Jinan Biomedicine Research and Development Center, College of Life Science and Technology, Institute of Biomedicine, Jinan University, Guangzhou, China
Lishan Zhong
Guangzhou Jinan Biomedicine Research and Development Center, College of Life Science and Technology, Institute of Biomedicine, Jinan University, Guangzhou, China
Jingyi Chen
Guangzhou Jinan Biomedicine Research and Development Center, College of Life Science and Technology, Institute of Biomedicine, Jinan University, Guangzhou, China
Zibo Zhao
Guangzhou Jinan Biomedicine Research and Development Center, College of Life Science and Technology, Institute of Biomedicine, Jinan University, Guangzhou, China
Rongze Wang
Guangzhou Jinan Biomedicine Research and Development Center, College of Life Science and Technology, Institute of Biomedicine, Jinan University, Guangzhou, China
Yexuan Zhu
Guangzhou Jinan Biomedicine Research and Development Center, College of Life Science and Technology, Institute of Biomedicine, Jinan University, Guangzhou, China
Junwei Liu
Guangzhou Jinan Biomedicine Research and Development Center, College of Life Science and Technology, Institute of Biomedicine, Jinan University, Guangzhou, China
Yanting Wu
Guangzhou Jinan Biomedicine Research and Development Center, College of Life Science and Technology, Institute of Biomedicine, Jinan University, Guangzhou, China
Cuifang Ye
Guangzhou Jinan Biomedicine Research and Development Center, College of Life Science and Technology, Institute of Biomedicine, Jinan University, Guangzhou, China; Corresponding author. Fujun Jin, School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510632, China.
Fujun Jin
School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, China; Corresponding author. Cuifang Ye, Institute of Biomedicine, Jinan University, Guangzhou 510632, China.
Zhe Ren
Guangzhou Jinan Biomedicine Research and Development Center, College of Life Science and Technology, Institute of Biomedicine, Jinan University, Guangzhou, China; Corresponding author. Zhe Ren, Institute of Biomedicine, Jinan University, Guangzhou 510632, China.
Obesity is a metabolic disease characterized by excessive fat storage, and the adipogenic differentiation of adipose-derived stromal cells (ADSCs) is closely linked to its occurrence. Growth differentiation factor 11 (GDF11), a well-known molecule in the field of anti-aging, also has great potential in regulating stem cell differentiation. In this study, we found that GDF11 inhibited adipogenic differentiation of human ADSCs in vitro by activating the WNT/β-catenin and SMAD2/3 pathways while inhibiting the AKT pathway. Moreover, the transcription factor Kruppel-like factor 15 (KLF15) was discovered to be an important downstream factor for GDF11 in inhibiting adipogenesis via the WNT/β-catenin pathway. Furthermore, AlphaFold2 structure prediction and inhibitor-blocking experiments revealed that ALK5 is a functional receptor of GDF11. Collectively, we demonstrated that GDF11 is a potential target for inhibiting adipogenic differentiation and combating obesity.
