Deciphering the interaction between Twist1 and PPARγ during adipocyte differentiation
Abstract Obesity, a worldwide epidemic in recent years, is mainly due to the uncontrolled development of adipose tissues, which includes adipocyte hypertrophy and hyperplasia. Adipocyte differentiation is a process involving multiple transcription factor cascades, and the exact mechanism has not yet...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-11-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-023-06283-0 |
| _version_ | 1797451312232660992 |
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| author | Leilei Sun Shaoping Ji Xuan Xie Lei Si Shaohao Liu Yao Lin Yahui Wang Zhenhua Song Na Fang Yang An Jian Yang |
| author_facet | Leilei Sun Shaoping Ji Xuan Xie Lei Si Shaohao Liu Yao Lin Yahui Wang Zhenhua Song Na Fang Yang An Jian Yang |
| author_sort | Leilei Sun |
| collection | DOAJ |
| description | Abstract Obesity, a worldwide epidemic in recent years, is mainly due to the uncontrolled development of adipose tissues, which includes adipocyte hypertrophy and hyperplasia. Adipocyte differentiation is a process involving multiple transcription factor cascades, and the exact mechanism has not yet been defined. As a bHLH transcription factor, Twist1 exerts its activity by forming homo- or heterodimers with other factors. In this study, we showed Twist1 restricts adipogenesis through PPARγ. Expression of various differentiation markers (including PPARγ and adiponectin) and triglyceride-containing lipid droplets were decreased with overexpression of Twist1. Pathway enrichment analysis of RNA-seq data showed that differentially expressed genes (DEGs) caused by Twist1 overexpression were significantly related to lipolysis and PPARγ signaling. This implicates that Twist1 plays important regulatory roles in these processes. ChIP and dual luciferase assays showed that Twist1 could bind either PPARγ or adiponectin promoter to repress their respective transcription or directly to PPARγ protein to regulate its transcriptional activity. Furthermore, Twist1 directly interacted RXRα, which usually forms heterodimer with PPARγ to regulate adipogenesis. Taken together, our results suggest that Twist1 is an inhibitory modulator of adipogenesis and its function is likely through direct interaction with PPARγ protein or its gene promoter. |
| first_indexed | 2024-03-09T14:51:53Z |
| format | Article |
| id | doaj.art-09fd94ba8d914c4e878f93403e4a5e2f |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-03-09T14:51:53Z |
| publishDate | 2023-11-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-09fd94ba8d914c4e878f93403e4a5e2f2023-11-26T14:22:47ZengNature Publishing GroupCell Death and Disease2041-48892023-11-01141111210.1038/s41419-023-06283-0Deciphering the interaction between Twist1 and PPARγ during adipocyte differentiationLeilei Sun0Shaoping Ji1Xuan Xie2Lei Si3Shaohao Liu4Yao Lin5Yahui Wang6Zhenhua Song7Na Fang8Yang An9Jian Yang10School of Basic Medical Sciences, Henan UniversitySchool of Basic Medical Sciences, Henan UniversitySchool of Basic Medical Sciences, Henan UniversitySchool of Basic Medical Sciences, Henan UniversitySchool of Basic Medical Sciences, Henan UniversitySchool of Basic Medical Sciences, Henan UniversitySchool of Basic Medical Sciences, Henan UniversitySchool of Basic Medical Sciences, Henan UniversitySchool of Basic Medical Sciences, Henan UniversitySchool of Basic Medical Sciences, Henan UniversityCollege of Pharmacy and Nutrition, University of SaskatchewanAbstract Obesity, a worldwide epidemic in recent years, is mainly due to the uncontrolled development of adipose tissues, which includes adipocyte hypertrophy and hyperplasia. Adipocyte differentiation is a process involving multiple transcription factor cascades, and the exact mechanism has not yet been defined. As a bHLH transcription factor, Twist1 exerts its activity by forming homo- or heterodimers with other factors. In this study, we showed Twist1 restricts adipogenesis through PPARγ. Expression of various differentiation markers (including PPARγ and adiponectin) and triglyceride-containing lipid droplets were decreased with overexpression of Twist1. Pathway enrichment analysis of RNA-seq data showed that differentially expressed genes (DEGs) caused by Twist1 overexpression were significantly related to lipolysis and PPARγ signaling. This implicates that Twist1 plays important regulatory roles in these processes. ChIP and dual luciferase assays showed that Twist1 could bind either PPARγ or adiponectin promoter to repress their respective transcription or directly to PPARγ protein to regulate its transcriptional activity. Furthermore, Twist1 directly interacted RXRα, which usually forms heterodimer with PPARγ to regulate adipogenesis. Taken together, our results suggest that Twist1 is an inhibitory modulator of adipogenesis and its function is likely through direct interaction with PPARγ protein or its gene promoter.https://doi.org/10.1038/s41419-023-06283-0 |
| spellingShingle | Leilei Sun Shaoping Ji Xuan Xie Lei Si Shaohao Liu Yao Lin Yahui Wang Zhenhua Song Na Fang Yang An Jian Yang Deciphering the interaction between Twist1 and PPARγ during adipocyte differentiation Cell Death and Disease |
| title | Deciphering the interaction between Twist1 and PPARγ during adipocyte differentiation |
| title_full | Deciphering the interaction between Twist1 and PPARγ during adipocyte differentiation |
| title_fullStr | Deciphering the interaction between Twist1 and PPARγ during adipocyte differentiation |
| title_full_unstemmed | Deciphering the interaction between Twist1 and PPARγ during adipocyte differentiation |
| title_short | Deciphering the interaction between Twist1 and PPARγ during adipocyte differentiation |
| title_sort | deciphering the interaction between twist1 and pparγ during adipocyte differentiation |
| url | https://doi.org/10.1038/s41419-023-06283-0 |
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