Full Text | PDF

Share on tweeters Share on facebook Share on linkedin Share on googleplus

Theranostics 2022; 12(18):7699-7716. doi:10.7150/thno.77102 This issue Cite

Research Paper

SOX4 promotes beige adipocyte-mediated adaptive thermogenesis by facilitating PRDM16-PPARγ complex

Huanming Shen1*, Ting He1*, Shuai Wang1*, Lingfeng Hou1*, Yixin Wei1, Yunjia Liu1, Chunli Mo1, Zehang Zhao1, WeiXin You1, Huiling Guo1✉, Boan Li1,2✉

1. 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 361100, Fujian, China.
2. Lead Contact.
* These authors contributed equally to this.

✉ Corresponding authors: Dr. Huiling Guo School of Life Sciences, Xiamen University, Xiang'an District, Xiamen, Fujian, China, 361102; Tel: 86-592-2186717; E-mail: ghuilingedu.cn. Dr. Boan Li School of Life Sciences, Xiamen University, Xiang'an D More

Citation:
Shen H, He T, Wang S, Hou L, Wei Y, Liu Y, Mo C, Zhao Z, You W, Guo H, Li B. SOX4 promotes beige adipocyte-mediated adaptive thermogenesis by facilitating PRDM16-PPARγ complex. Theranostics 2022; 12(18):7699-7716. doi:10.7150/thno.77102. https://www.thno.org/v12p7699.htm
Other styles

File import instruction

Abstract

Graphic abstract

Brown and beige fat protect against cold environments and obesity by catabolizing stored energy to generate heat. This process is achieved by controlling thermogenesis-related gene expression and the development of brown/beige fat through the induction of transcription factors, most notably PPARγ. However, the cofactors that induce the expression of thermogenic genes with PPARγ are still not well understood. In this study, we explored the role of SOX4 in adaptive thermogenesis and its relationship with PPARγ.

Methods: Whole transcriptome deep sequencing (RNA-seq) analysis of inguinal subcutaneous white adipose tissue (iWAT) after cold stimulation was performed to identify genes with differential expression in mice. Indirect calorimetry detected oxygen consumption rate and heat generation. mRNA levels were analyzed by qPCR assays. Proteins were detected by immunoblotting and immunofluorescence. Interaction of proteins was detected by endogenous and exogenous Co-IP. ChIP-qPCR, FAIRE assay and luciferase reporter assays were used to investigate transcriptional regulation.

Results: SOX4 was identified as the main transcriptional effector of thermogenesis. Mice with either adipocyte-specific or UCP1+ cells deletion of SOX4 exhibited significant cold intolerance, decreased energy expenditure, and beige adipocyte formation, which was attributed to decreased thermogenic gene expression. In addition, these mice developed obesity on a high-fat diet, with severe hepatic steatosis, insulin resistance, and inflammation. At the cell level, loss of SOX4 from preadipocytes inhibited the development of beige adipocytes, and loss of SOX4 from mature beige adipocytes reduced the expression of thermogenesis-related genes and energy metabolism. Mechanistically, SOX4 stimulated the transcriptional activity of Ucp1 by binding to PPARγ and activating its transcriptional function. These actions of SOX4 were, at least partly, mediated by recruiting PRDM16 to PPARγ, thus forming a transcriptional complex to elevate the expression of thermogenic genes.

Conclusion: SOX4, as a coactivator of PPARγ, drives the thermogenic gene expression program and thermogenesis of beige fat, promoting energy expenditure. It has important physiological significance in resisting cold and obesity.

Keywords: beige fat, thermogenesis, obesity, PPARγ, SOX4.

Citation styles

APA
Shen, H., He, T., Wang, S., Hou, L., Wei, Y., Liu, Y., Mo, C., Zhao, Z., You, W., Guo, H., Li, B. (2022). SOX4 promotes beige adipocyte-mediated adaptive thermogenesis by facilitating PRDM16-PPARγ complex. Theranostics, 12(18), 7699-7716. https://doi.org/10.7150/thno.77102.

ACS
Shen, H.; He, T.; Wang, S.; Hou, L.; Wei, Y.; Liu, Y.; Mo, C.; Zhao, Z.; You, W.; Guo, H.; Li, B. SOX4 promotes beige adipocyte-mediated adaptive thermogenesis by facilitating PRDM16-PPARγ complex. Theranostics 2022, 12 (18), 7699-7716. DOI: 10.7150/thno.77102.

NLM
Shen H, He T, Wang S, Hou L, Wei Y, Liu Y, Mo C, Zhao Z, You W, Guo H, Li B. SOX4 promotes beige adipocyte-mediated adaptive thermogenesis by facilitating PRDM16-PPARγ complex. Theranostics 2022; 12(18):7699-7716. doi:10.7150/thno.77102. https://www.thno.org/v12p7699.htm

CSE
Shen H, He T, Wang S, Hou L, Wei Y, Liu Y, Mo C, Zhao Z, You W, Guo H, Li B. 2022. SOX4 promotes beige adipocyte-mediated adaptive thermogenesis by facilitating PRDM16-PPARγ complex. Theranostics. 12(18):7699-7716.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Popup Image

©2024 Ivyspring International Publisher. Terms of use