Rna M6a Methylation Regulates Glycolysis of Beige Fat and Contributes to Systemic Metabolic Homeostasis
Abstract N6‐methyladenosine (m6A) modification has been implicated in the progression of obesity and metabolic diseases. However, its impact on beige fat biology is not well understood. Here, via m6A‐sequencing and RNA‐sequencing, this work reports that upon beige adipocytes activation, glycolytic g...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-09-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202300436 |
| _version_ | 1797692680129478656 |
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| author | Yu Li Yankang Zhang Ting Zhang Xiaodan Ping Dongmei Wang Yanru Chen Jian Yu Caizhi Liu Ziqi Liu Yuhan Zheng Yongfeng Yang Chengchao Ruan Dali Li Zhenyu Du Jiqiu Wang Lingyan Xu Xinran Ma |
| author_facet | Yu Li Yankang Zhang Ting Zhang Xiaodan Ping Dongmei Wang Yanru Chen Jian Yu Caizhi Liu Ziqi Liu Yuhan Zheng Yongfeng Yang Chengchao Ruan Dali Li Zhenyu Du Jiqiu Wang Lingyan Xu Xinran Ma |
| author_sort | Yu Li |
| collection | DOAJ |
| description | Abstract N6‐methyladenosine (m6A) modification has been implicated in the progression of obesity and metabolic diseases. However, its impact on beige fat biology is not well understood. Here, via m6A‐sequencing and RNA‐sequencing, this work reports that upon beige adipocytes activation, glycolytic genes undergo major events of m6A modification and transcriptional activation. Genetic ablation of m6A writer Mettl3 in fat tissues reveals that Mettl3 deficiency in mature beige adipocytes leads to suppressed glycolytic capability and thermogenesis, as well as reduced preadipocytes proliferation via glycolytic product lactate. In addition, specific modulation of Mettl3 in beige fat via AAV delivery demonstrates consistently Mettl3's role in glucose metabolism, thermogenesis, and beige fat hyperplasia. Mechanistically, Mettl3 and m6A reader Igf2bp2 control mRNA stability of key glycolytic genes in beige adipocytes. Overall, these findings highlight the significance of m6A on fat biology and systemic energy homeostasis. |
| first_indexed | 2024-03-12T02:32:05Z |
| format | Article |
| id | doaj.art-9eb86d1ceb77483dbe0097621f6abf1f |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-03-12T02:32:05Z |
| publishDate | 2023-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-9eb86d1ceb77483dbe0097621f6abf1f2023-09-05T07:49:09ZengWileyAdvanced Science2198-38442023-09-011025n/an/a10.1002/advs.202300436Rna M6a Methylation Regulates Glycolysis of Beige Fat and Contributes to Systemic Metabolic HomeostasisYu Li0Yankang Zhang1Ting Zhang2Xiaodan Ping3Dongmei Wang4Yanru Chen5Jian Yu6Caizhi Liu7Ziqi Liu8Yuhan Zheng9Yongfeng Yang10Chengchao Ruan11Dali Li12Zhenyu Du13Jiqiu Wang14Lingyan Xu15Xinran Ma16Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life Sciences East China Normal University Shanghai 200241ChinaShanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life Sciences East China Normal University Shanghai 200241ChinaShanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life Sciences East China Normal University Shanghai 200241ChinaShanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life Sciences East China Normal University Shanghai 200241ChinaShanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life Sciences East China Normal University Shanghai 200241ChinaDepartment of Endocrinology and Metabolism Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025ChinaShanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life Sciences East China Normal University Shanghai 200241ChinaShanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life Sciences East China Normal University Shanghai 200241ChinaShanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life Sciences East China Normal University Shanghai 200241ChinaShanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life Sciences East China Normal University Shanghai 200241ChinaDepartment of Physiology and Pathophysiology School of Basic Medical Sciences Fudan University Shanghai 200032ChinaDepartment of Physiology and Pathophysiology School of Basic Medical Sciences Fudan University Shanghai 200032ChinaShanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life Sciences East China Normal University Shanghai 200241ChinaShanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life Sciences East China Normal University Shanghai 200241ChinaDepartment of Endocrinology and Metabolism Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025ChinaShanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life Sciences East China Normal University Shanghai 200241ChinaShanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life Sciences East China Normal University Shanghai 200241ChinaAbstract N6‐methyladenosine (m6A) modification has been implicated in the progression of obesity and metabolic diseases. However, its impact on beige fat biology is not well understood. Here, via m6A‐sequencing and RNA‐sequencing, this work reports that upon beige adipocytes activation, glycolytic genes undergo major events of m6A modification and transcriptional activation. Genetic ablation of m6A writer Mettl3 in fat tissues reveals that Mettl3 deficiency in mature beige adipocytes leads to suppressed glycolytic capability and thermogenesis, as well as reduced preadipocytes proliferation via glycolytic product lactate. In addition, specific modulation of Mettl3 in beige fat via AAV delivery demonstrates consistently Mettl3's role in glucose metabolism, thermogenesis, and beige fat hyperplasia. Mechanistically, Mettl3 and m6A reader Igf2bp2 control mRNA stability of key glycolytic genes in beige adipocytes. Overall, these findings highlight the significance of m6A on fat biology and systemic energy homeostasis.https://doi.org/10.1002/advs.202300436beige fatenergy homeostasisglycolysisN6‐methyladenosineMettl3preadipocytes proliferation |
| spellingShingle | Yu Li Yankang Zhang Ting Zhang Xiaodan Ping Dongmei Wang Yanru Chen Jian Yu Caizhi Liu Ziqi Liu Yuhan Zheng Yongfeng Yang Chengchao Ruan Dali Li Zhenyu Du Jiqiu Wang Lingyan Xu Xinran Ma Rna M6a Methylation Regulates Glycolysis of Beige Fat and Contributes to Systemic Metabolic Homeostasis Advanced Science beige fat energy homeostasis glycolysis N6‐methyladenosine Mettl3 preadipocytes proliferation |
| title | Rna M6a Methylation Regulates Glycolysis of Beige Fat and Contributes to Systemic Metabolic Homeostasis |
| title_full | Rna M6a Methylation Regulates Glycolysis of Beige Fat and Contributes to Systemic Metabolic Homeostasis |
| title_fullStr | Rna M6a Methylation Regulates Glycolysis of Beige Fat and Contributes to Systemic Metabolic Homeostasis |
| title_full_unstemmed | Rna M6a Methylation Regulates Glycolysis of Beige Fat and Contributes to Systemic Metabolic Homeostasis |
| title_short | Rna M6a Methylation Regulates Glycolysis of Beige Fat and Contributes to Systemic Metabolic Homeostasis |
| title_sort | rna m6a methylation regulates glycolysis of beige fat and contributes to systemic metabolic homeostasis |
| topic | beige fat energy homeostasis glycolysis N6‐methyladenosine Mettl3 preadipocytes proliferation |
| url | https://doi.org/10.1002/advs.202300436 |
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