Suppression of preadipocyte determination by SOX4 limits white adipocyte hyperplasia in obesity
Ting He,
Shuai Wang,
Shengnan Li,
Huanming Shen,
Lingfeng Hou,
Yunjia Liu,
Yixin Wei,
Fuan Xie,
Zhiming Zhang,
Zehang Zhao,
Chunli Mo,
Huiling Guo,
Qingsong Huang,
Rui Zhang,
Dongyan Shen,
Boan Li
Affiliations
Ting He
State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network and Engineering Research Center of Molecular Diagnostics of The Ministry of Education, School of Life Sciences, Xiamen University, Xiamen, Fujian 361100, China
Shuai Wang
State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network and Engineering Research Center of Molecular Diagnostics of The Ministry of Education, School of Life Sciences, Xiamen University, Xiamen, Fujian 361100, China
Shengnan Li
State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network and Engineering Research Center of Molecular Diagnostics of The Ministry of Education, School of Life Sciences, Xiamen University, Xiamen, Fujian 361100, China; School of Medicine, Henan Polytechnic University, Jiaozuo, Henan 454000, China
Huanming Shen
State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network and Engineering Research Center of Molecular Diagnostics of The Ministry of Education, School of Life Sciences, Xiamen University, Xiamen, Fujian 361100, China
Lingfeng Hou
State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network and Engineering Research Center of Molecular Diagnostics of The Ministry of Education, School of Life Sciences, Xiamen University, Xiamen, Fujian 361100, China
Yunjia Liu
State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network and Engineering Research Center of Molecular Diagnostics of The Ministry of Education, School of Life Sciences, Xiamen University, Xiamen, Fujian 361100, China
Yixin Wei
State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network and Engineering Research Center of Molecular Diagnostics of The Ministry of Education, School of Life Sciences, Xiamen University, Xiamen, Fujian 361100, China
Fuan Xie
Xiamen University Research Center of Retroperitoneal, Tumor Committee of Oncology Society of Chinese Medical Association, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China
Zhiming Zhang
Xiamen Cell Therapy Research Center, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian 361003, China
Zehang Zhao
State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network and Engineering Research Center of Molecular Diagnostics of The Ministry of Education, School of Life Sciences, Xiamen University, Xiamen, Fujian 361100, China
Chunli Mo
State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network and Engineering Research Center of Molecular Diagnostics of The Ministry of Education, School of Life Sciences, Xiamen University, Xiamen, Fujian 361100, China
Huiling Guo
State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network and Engineering Research Center of Molecular Diagnostics of The Ministry of Education, School of Life Sciences, Xiamen University, Xiamen, Fujian 361100, China
Qingsong Huang
State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network and Engineering Research Center of Molecular Diagnostics of The Ministry of Education, School of Life Sciences, Xiamen University, Xiamen, Fujian 361100, China
Rui Zhang
Xiamen Cell Therapy Research Center, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian 361003, China; Corresponding author
Dongyan Shen
Xiamen Cell Therapy Research Center, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian 361003, China; Corresponding author
Boan Li
State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network and Engineering Research Center of Molecular Diagnostics of The Ministry of Education, School of Life Sciences, Xiamen University, Xiamen, Fujian 361100, China; Corresponding author
Summary: Preadipocyte determination expanding the pool of preadipocytes is a vital process in adipocyte hyperplasia, but the molecular mechanisms underlying this process are yet to be elucidated. Herein, SRY-related HMG box transcription factor 4 (SOX4) was identified as a critical target in response to BMP4- and TGFβ-regulated preadipocyte determination. SOX4 deficiency is sufficient to promote preadipocyte determination in mesenchymal stem cells (MSCs) and acquisition of preadipocyte properties in nonadipogenic lineages, while its overexpression impairs the adipogenic capacity of preadipocytes and converts them into nonadipogenic lineages. Mechanism studies indicated that SOX4 activates and cooperates with LEF1 to retain the nuclear localization of β-catenin, thus mediating the crosstalk between TGFβ/BMP4 signaling pathway and Wnt signaling pathway to regulate the preadipocyte determination. In vivo studies demonstrated that SOX4 promotes the adipogenic-nonadipogenic conversion and suppresses the adipocyte hyperplasia. Together, our findings highlight the importance of SOX4 in regulating the adipocyte hyperplasia in obesity.
