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

Heliyon (Feb 2023)

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.

Journal volume & issue: Vol. 9, no. 2
p. e13088

Abstract

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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.

Published in Heliyon

ISSN: 2405-8440 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Science: Science (General); Social Sciences: Social sciences (General)
Website: https://www.cell.com/heliyon/home

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