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

doi:10.1016/j.heliyon.2023.e13088

GDF11 inhibits adipogenesis of human adipose-derived stromal cells through ALK5/KLF15/β-catenin/PPARγ cascade

Heliyon. 2023 Jan 21;9(2):e13088. doi: 10.1016/j.heliyon.2023.e13088. eCollection 2023 Feb.

Authors

Shimin Lin¹, Lishan Zhong¹, Jingyi Chen¹, Zibo Zhao¹, Rongze Wang¹, Yexuan Zhu¹, Junwei Liu¹, Yanting Wu¹, Cuifang Ye¹, Fujun Jin², Zhe Ren¹

Affiliations

¹ Guangzhou Jinan Biomedicine Research and Development Center, College of Life Science and Technology, Institute of Biomedicine, Jinan University, Guangzhou, China.
² School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, China.

Abstract

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.

Keywords: Adipogenesis; GDF11; KLF15; Obesity; PPARγ; WNT/β-catenin pathway.