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• W4283807179 abstract "Article4 July 2022 Transparent process PGE2-EP3 axis promotes brown adipose tissue formation through stabilization of WTAP RNA methyltransferase Xixi Tao Xixi Tao orcid.org/0000-0002-4116-0487 Department of Pharmacology, Tianjin Key Laboratory of Inflammatory Biology, Center for Cardiovascular Diseases, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China Contribution: Resources, Data curation, Software, Formal analysis, Validation, Visualization, Methodology Search for more papers by this author Ronglu Du Ronglu Du orcid.org/0000-0001-9327-7073 Department of Pharmacology, Tianjin Key Laboratory of Inflammatory Biology, Center for Cardiovascular Diseases, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China Contribution: Resources, Data curation, Software, Formal analysis, Validation, Visualization, Methodology Search for more papers by this author Shumin Guo Shumin Guo Department of Pharmacology, Tianjin Key Laboratory of Inflammatory Biology, Center for Cardiovascular Diseases, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China Contribution: Resources, Data curation, Software, Formal analysis, Validation, Visualization, Methodology Search for more papers by this author Xiangling Feng Xiangling Feng orcid.org/0000-0003-4668-6709 Department of Pharmacology, Tianjin Key Laboratory of Inflammatory Biology, Center for Cardiovascular Diseases, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China Contribution: Resources, Data curation, Software, Formal analysis, Validation, Visualization, Methodology Search for more papers by this author Tingting Yu Tingting Yu Department of Pharmacology, Tianjin Key Laboratory of Inflammatory Biology, Center for Cardiovascular Diseases, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China Contribution: Data curation, Software, Formal analysis, Methodology Search for more papers by this author Qian OuYang Qian OuYang State Key Laboratory of Pharmaceutical Biotechnology, MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, China Contribution: Resources, Data curation, Software, Visualization, Methodology Search for more papers by this author Qiaoli Chen Qiaoli Chen orcid.org/0000-0002-0102-1351 State Key Laboratory of Pharmaceutical Biotechnology, MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, China Contribution: Resources, Data curation, Software, Visualization, Methodology Search for more papers by this author Xutong Fan Xutong Fan orcid.org/0000-0001-7056-1995 Department of Pharmacology, Tianjin Key Laboratory of Inflammatory Biology, Center for Cardiovascular Diseases, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China Contribution: Resources, Data curation, Software, Visualization, Methodology Search for more papers by this author Xueqi Wang Xueqi Wang Department of Pharmacology, Tianjin Key Laboratory of Inflammatory Biology, Center for Cardiovascular Diseases, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China Contribution: Resources, Methodology Search for more papers by this author Chen Guo Chen Guo Department of Gynecology and Obstetrics, Tianjin Key Laboratory of Female Reproductive Health and Eugenics, Tianjin Medical University General Hospital, Tianjin, China Contribution: Resources, Methodology Search for more papers by this author Xiaozhou Li Xiaozhou Li Department of Gynecology and Obstetrics, Tianjin Key Laboratory of Female Reproductive Health and Eugenics, Tianjin Medical University General Hospital, Tianjin, China Contribution: Resources, Funding acquisition, Methodology Search for more papers by this author Fengxia Xue Fengxia Xue Department of Gynecology and Obstetrics, Tianjin Key Laboratory of Female Reproductive Health and Eugenics, Tianjin Medical University General Hospital, Tianjin, China Contribution: Resources, Funding acquisition, Methodology Search for more papers by this author Shuai Chen Shuai Chen State Key Laboratory of Pharmaceutical Biotechnology, MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, China Contribution: Resources, Supervision, Methodology Search for more papers by this author Minghan Tong Minghan Tong State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China Contribution: Resources Search for more papers by this author Michael Lazarus Michael Lazarus orcid.org/0000-0003-3863-4474 International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba City, Japan Contribution: Resources Search for more papers by this author Shengkai Zuo Shengkai Zuo Department of Pharmacology, Tianjin Key Laboratory of Inflammatory Biology, Center for Cardiovascular Diseases, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China Contribution: Data curation, Software, Formal analysis, Visualization, Methodology Search for more papers by this author Ying Yu Corresponding Author Ying Yu [email protected] orcid.org/0000-0002-6476-1752 Department of Pharmacology, Tianjin Key Laboratory of Inflammatory Biology, Center for Cardiovascular Diseases, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China Contribution: Conceptualization, Resources, Supervision, Funding acquisition, ​Investigation, Project administration, Writing - review & editing Search for more papers by this author Yujun Shen Corresponding Author Yujun Shen [email protected] orcid.org/0000-0002-9266-9064 Department of Pharmacology, Tianjin Key Laboratory of Inflammatory Biology, Center for Cardiovascular Diseases, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China Contribution: Conceptualization, Resources, Data curation, Software, Formal analysis, Supervision, Funding acquisition, Validation, ​Investigation, Visualization, Methodology, Writing - original draft, Project administration, Writing - review & editing Search for more papers by this author Xixi Tao Xixi Tao orcid.org/0000-0002-4116-0487 Department of Pharmacology, Tianjin Key Laboratory of Inflammatory Biology, Center for Cardiovascular Diseases, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China Contribution: Resources, Data curation, Software, Formal analysis, Validation, Visualization, Methodology Search for more papers by this author Ronglu Du Ronglu Du orcid.org/0000-0001-9327-7073 Department of Pharmacology, Tianjin Key Laboratory of Inflammatory Biology, Center for Cardiovascular Diseases, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China Contribution: Resources, Data curation, Software, Formal analysis, Validation, Visualization, Methodology Search for more papers by this author Shumin Guo Shumin Guo Department of Pharmacology, Tianjin Key Laboratory of Inflammatory Biology, Center for Cardiovascular Diseases, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China Contribution: Resources, Data curation, Software, Formal analysis, Validation, Visualization, Methodology Search for more papers by this author Xiangling Feng Xiangling Feng orcid.org/0000-0003-4668-6709 Department of Pharmacology, Tianjin Key Laboratory of Inflammatory Biology, Center for Cardiovascular Diseases, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China Contribution: Resources, Data curation, Software, Formal analysis, Validation, Visualization, Methodology Search for more papers by this author Tingting Yu Tingting Yu Department of Pharmacology, Tianjin Key Laboratory of Inflammatory Biology, Center for Cardiovascular Diseases, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China Contribution: Data curation, Software, Formal analysis, Methodology Search for more papers by this author Qian OuYang Qian OuYang State Key Laboratory of Pharmaceutical Biotechnology, MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, China Contribution: Resources, Data curation, Software, Visualization, Methodology Search for more papers by this author Qiaoli Chen Qiaoli Chen orcid.org/0000-0002-0102-1351 State Key Laboratory of Pharmaceutical Biotechnology, MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, China Contribution: Resources, Data curation, Software, Visualization, Methodology Search for more papers by this author Xutong Fan Xutong Fan orcid.org/0000-0001-7056-1995 Department of Pharmacology, Tianjin Key Laboratory of Inflammatory Biology, Center for Cardiovascular Diseases, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China Contribution: Resources, Data curation, Software, Visualization, Methodology Search for more papers by this author Xueqi Wang Xueqi Wang Department of Pharmacology, Tianjin Key Laboratory of Inflammatory Biology, Center for Cardiovascular Diseases, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China Contribution: Resources, Methodology Search for more papers by this author Chen Guo Chen Guo Department of Gynecology and Obstetrics, Tianjin Key Laboratory of Female Reproductive Health and Eugenics, Tianjin Medical University General Hospital, Tianjin, China Contribution: Resources, Methodology Search for more papers by this author Xiaozhou Li Xiaozhou Li Department of Gynecology and Obstetrics, Tianjin Key Laboratory of Female Reproductive Health and Eugenics, Tianjin Medical University General Hospital, Tianjin, China Contribution: Resources, Funding acquisition, Methodology Search for more papers by this author Fengxia Xue Fengxia Xue Department of Gynecology and Obstetrics, Tianjin Key Laboratory of Female Reproductive Health and Eugenics, Tianjin Medical University General Hospital, Tianjin, China Contribution: Resources, Funding acquisition, Methodology Search for more papers by this author Shuai Chen Shuai Chen State Key Laboratory of Pharmaceutical Biotechnology, MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, China Contribution: Resources, Supervision, Methodology Search for more papers by this author Minghan Tong Minghan Tong State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China Contribution: Resources Search for more papers by this author Michael Lazarus Michael Lazarus orcid.org/0000-0003-3863-4474 International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba City, Japan Contribution: Resources Search for more papers by this author Shengkai Zuo Shengkai Zuo Department of Pharmacology, Tianjin Key Laboratory of Inflammatory Biology, Center for Cardiovascular Diseases, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China Contribution: Data curation, Software, Formal analysis, Visualization, Methodology Search for more papers by this author Ying Yu Corresponding Author Ying Yu [email protected] orcid.org/0000-0002-6476-1752 Department of Pharmacology, Tianjin Key Laboratory of Inflammatory Biology, Center for Cardiovascular Diseases, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China Contribution: Conceptualization, Resources, Supervision, Funding acquisition, ​Investigation, Project administration, Writing - review & editing Search for more papers by this author Yujun Shen Corresponding Author Yujun Shen [email protected] orcid.org/0000-0002-9266-9064 Department of Pharmacology, Tianjin Key Laboratory of Inflammatory Biology, Center for Cardiovascular Diseases, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China Contribution: Conceptualization, Resources, Data curation, Software, Formal analysis, Supervision, Funding acquisition, Validation, ​Investigation, Visualization, Methodology, Writing - original draft, Project administration, Writing - review & editing Search for more papers by this author Author Information Xixi Tao1,†, Ronglu Du1,†, Shumin Guo1,†, Xiangling Feng1, Tingting Yu1, Qian OuYang2, Qiaoli Chen2, Xutong Fan1, Xueqi Wang1, Chen Guo3, Xiaozhou Li3, Fengxia Xue3, Shuai Chen2, Minghan Tong4, Michael Lazarus5, Shengkai Zuo1, Ying Yu *,1 and Yujun Shen *,1 1Department of Pharmacology, Tianjin Key Laboratory of Inflammatory Biology, Center for Cardiovascular Diseases, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China 2State Key Laboratory of Pharmaceutical Biotechnology, MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, China 3Department of Gynecology and Obstetrics, Tianjin Key Laboratory of Female Reproductive Health and Eugenics, Tianjin Medical University General Hospital, Tianjin, China 4State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China 5International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba City, Japan † These authors contributed equally to this work *Corresponding author. Tel: +86 22 83336627; E-mail: [email protected] author. Tel: +86 22 83336642; E-mail: [email protected] The EMBO Journal (2022)41:e110439https://doi.org/10.15252/embj.2021110439 Full textView the full text of the articlePDFDownload PDF of article text and main figures. Peer ReviewDownload a summary of the editorial decision process including editorial decision letters, reviewer comments and author responses to feedback. ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions Figures & Info Abstract Brown adipose tissue (BAT) functions as a thermogenic organ and is negatively associated with cardiometabolic diseases. N6-methyladenosine (m6A) modulation regulates the fate of stem cells. Here, we show that the prostaglandin E2 (PGE2)–E-prostanoid receptor 3 (EP3) axis was activated during mouse interscapular BAT development. Disruption of EP3 impaired the browning process during adipocyte differentiation from pre-adipocytes. Brown adipocyte-specific depletion of EP3 compromised interscapular BAT formation and aggravated high-fat diet-induced obesity and insulin resistance in vivo. Mechanistically, activation of EP3 stabilized the Zfp410 mRNA via WTAP-mediated m6A modification, while knockdown of Zfp410 abolished the EP3-induced enhancement of brown adipogenesis. EP3 prevented ubiquitin-mediated degradation of WTAP by eliminating PKA-mediated ERK1/2 inhibition during brown adipocyte differentiation. Ablation of WTAP in brown adipocytes abrogated the protective effect of EP3 overexpression in high-fat diet-fed mice. Inhibition of EP3 also retarded human embryonic stem cell differentiation into mature brown adipocytes by reducing the WTAP levels. Thus, a conserved PGE2-EP3 axis promotes BAT development by stabilizing WTAP/Zfp410 signaling in a PKA/ERK1/2-dependent manner. Synopsis Development of brown adipose tissue (BAT) is tightly regulated by transcriptional and epigenetic reprogramming, but its upstream regulation remains poorly understood. Here, prostaglandin receptor signalling is shown to be a key promoter of brown adipogenesis enhancing expression of thermogenic gene programs. The PGE2/EP3 axis is activated during the development of interscapular BAT in mice. BAT-specific depletion of EP3 results in adipocyte whitening and aggravated diet-induced obesity. Loss of EP3 accelerates ubiquitin-mediated degradation of N6-methyladenosine methyltransferase WTAP, decreasing m6A-dependent mRNA stability of brown gene transcription factor Zfp410. EP3 receptor-mediated control of brown adipogenesis is conserved in human embryonic stem cell differentiation. Previous ArticleNext Article Read MoreAbout the coverClose modalView large imageVolume 41,Issue 16,16 August 2022This cover highlights the article Cryo‐EM reveals mechanisms of angiotensin I‐converting enzyme allostery and dimerization by Lizelle Lubbe, Edward D. Sturrock and colleagues. Angiotensin I‐converting enzyme (ACE) is crucial for blood pressure regulation. Here, we reveal the first structures of monomeric and dimeric ACE using cryo‐EM, and uncover mechanistic insights which light the way for the development of novel drugs to treat cardiovascular disease. This image illustrates how dimerization increases domain motions (cyan), activates a newly identified allosteric switch (yellow loop), and triggers key active site changes (yellow glow). The background shows 2D views of ACE, reminiscent of a cryo‐EM micrograph.(Scientific image by Lizelle Lubbe) Volume 41Issue 1616 August 2022In this issue ReferencesRelatedDetailsLoading ..." @default.
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• W4283807179 title "<scp>PGE₂‐EP3</scp> axis promotes brown adipose tissue formation through stabilization of <scp>WTAP RNA</scp> methyltransferase" @default.
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