The Phytochemical Rhein Mediates M6A-Independent Suppression of Adipocyte Differentiation
Adipogenesis is mediated by the complex gene expression networks involving the posttranscriptional modifications. The natural compound rhein has been linked to the regulation of adipogenesis, but the underlying regulatory mechanisms remain elusive. Herein, we systematically analyzed the effects of r...
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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Nutrition |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnut.2021.756803/full |
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| author | Linyuan Huang Jun Zhang Xinyun Zhu Xue Mi Qiujie Li Jing Gao Jianheng Zhou Jun Zhou Jun Zhou Xiao-Min Liu |
| author_facet | Linyuan Huang Jun Zhang Xinyun Zhu Xue Mi Qiujie Li Jing Gao Jianheng Zhou Jun Zhou Jun Zhou Xiao-Min Liu |
| author_sort | Linyuan Huang |
| collection | DOAJ |
| description | Adipogenesis is mediated by the complex gene expression networks involving the posttranscriptional modifications. The natural compound rhein has been linked to the regulation of adipogenesis, but the underlying regulatory mechanisms remain elusive. Herein, we systematically analyzed the effects of rhein on adipogenesis at both the transcriptional and posttranscriptional levels. Rhein remarkably suppresses adipogenesis in the stage-specific and dose-dependent manners. Rhein has been identified to inhibit fat mass and obesity-associated (FTO) demethylase activity. Surprisingly, side-by-side comparison analysis revealed that the rhein treatment and Fto knockdown triggered the differential gene regulatory patterns, resulting in impaired adipocyte formation. Specifically, rhein treatment mildly altered the transcriptome with hundreds of genes dysregulated. N6-methyladenosine (m6A) methylome profile showed that, although the supply of rhein induced increased m6A levels on a small subset of messenger RNAs (mRNAs), few of them showed dramatic transcriptional response to this compound. Moreover, the specific rhein-responsive mRNAs, which are linked to mitotic pathway, are barely methylated or contain m6A peaks without dramatic response to rhein, suggesting separate regulation of global m6A pattern and adipogenesis mediated by rhein. Further identification of m6A-independent pathways revealed a positive regulator, receptor expressing-enhancing protein 3 (REEP3), in guidance of adipogenesis. Hence, this study provides the mechanistic view of the cellular actions of rhein in the modulation of adipogenesis and identifies a potential novel target for obesity therapeutic research. |
| first_indexed | 2024-12-19T18:19:19Z |
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| institution | Directory Open Access Journal |
| issn | 2296-861X |
| language | English |
| last_indexed | 2024-12-19T18:19:19Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Nutrition |
| spelling | doaj.art-ecb635dbb8f44908a39556d5693074bf2022-12-21T20:11:01ZengFrontiers Media S.A.Frontiers in Nutrition2296-861X2021-11-01810.3389/fnut.2021.756803756803The Phytochemical Rhein Mediates M6A-Independent Suppression of Adipocyte DifferentiationLinyuan Huang0Jun Zhang1Xinyun Zhu2Xue Mi3Qiujie Li4Jing Gao5Jianheng Zhou6Jun Zhou7Jun Zhou8Xiao-Min Liu9School of Life Science and Technology, China Pharmaceutical University, Nanjing, ChinaSchool of Life Science and Technology, China Pharmaceutical University, Nanjing, ChinaSchool of Life Science and Technology, China Pharmaceutical University, Nanjing, ChinaSchool of Life Science and Technology, China Pharmaceutical University, Nanjing, ChinaSchool of Life Science and Technology, China Pharmaceutical University, Nanjing, ChinaSchool of Life Science and Technology, China Pharmaceutical University, Nanjing, ChinaSchool of Life Science and Technology, China Pharmaceutical University, Nanjing, ChinaSchool of Life Science and Technology, China Pharmaceutical University, Nanjing, ChinaState Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, ChinaSchool of Life Science and Technology, China Pharmaceutical University, Nanjing, ChinaAdipogenesis is mediated by the complex gene expression networks involving the posttranscriptional modifications. The natural compound rhein has been linked to the regulation of adipogenesis, but the underlying regulatory mechanisms remain elusive. Herein, we systematically analyzed the effects of rhein on adipogenesis at both the transcriptional and posttranscriptional levels. Rhein remarkably suppresses adipogenesis in the stage-specific and dose-dependent manners. Rhein has been identified to inhibit fat mass and obesity-associated (FTO) demethylase activity. Surprisingly, side-by-side comparison analysis revealed that the rhein treatment and Fto knockdown triggered the differential gene regulatory patterns, resulting in impaired adipocyte formation. Specifically, rhein treatment mildly altered the transcriptome with hundreds of genes dysregulated. N6-methyladenosine (m6A) methylome profile showed that, although the supply of rhein induced increased m6A levels on a small subset of messenger RNAs (mRNAs), few of them showed dramatic transcriptional response to this compound. Moreover, the specific rhein-responsive mRNAs, which are linked to mitotic pathway, are barely methylated or contain m6A peaks without dramatic response to rhein, suggesting separate regulation of global m6A pattern and adipogenesis mediated by rhein. Further identification of m6A-independent pathways revealed a positive regulator, receptor expressing-enhancing protein 3 (REEP3), in guidance of adipogenesis. Hence, this study provides the mechanistic view of the cellular actions of rhein in the modulation of adipogenesis and identifies a potential novel target for obesity therapeutic research.https://www.frontiersin.org/articles/10.3389/fnut.2021.756803/fullrheinN6-methyladenosineadipocytedifferentiationmitotic clonal expansionREEP3 |
| spellingShingle | Linyuan Huang Jun Zhang Xinyun Zhu Xue Mi Qiujie Li Jing Gao Jianheng Zhou Jun Zhou Jun Zhou Xiao-Min Liu The Phytochemical Rhein Mediates M6A-Independent Suppression of Adipocyte Differentiation Frontiers in Nutrition rhein N6-methyladenosine adipocyte differentiation mitotic clonal expansion REEP3 |
| title | The Phytochemical Rhein Mediates M6A-Independent Suppression of Adipocyte Differentiation |
| title_full | The Phytochemical Rhein Mediates M6A-Independent Suppression of Adipocyte Differentiation |
| title_fullStr | The Phytochemical Rhein Mediates M6A-Independent Suppression of Adipocyte Differentiation |
| title_full_unstemmed | The Phytochemical Rhein Mediates M6A-Independent Suppression of Adipocyte Differentiation |
| title_short | The Phytochemical Rhein Mediates M6A-Independent Suppression of Adipocyte Differentiation |
| title_sort | phytochemical rhein mediates m6a independent suppression of adipocyte differentiation |
| topic | rhein N6-methyladenosine adipocyte differentiation mitotic clonal expansion REEP3 |
| url | https://www.frontiersin.org/articles/10.3389/fnut.2021.756803/full |
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