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The hepatic AMPK-TET1-SIRT1 axis regulates glucose homeostasis

Ten-eleven translocation methylcytosine dioxygenase 1 (TET1) is involved in multiple biological functions in cell development, differentiation, and transcriptional regulation. Tet1 deficient mice display the defects of murine glucose metabolism. However, the role of TET1 in metabolic homeostasis kee...

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Autores principales: Zhang, Chunbo, Zhong, Tianyu, Li, Yuanyuan, Li, Xianfeng, Yuan, Xiaopeng, Liu, Linlin, Wu, Weilin, Wu, Jing, Wu, Ye, Liang, Rui, Xie, Xinhua, Kang, Chuanchuan, Liu, Yuwen, Lai, Zhonghong, Xiao, Jianbo, Tang, Zhixian, Jin, Riqun, Wang, Yan, Xiao, Yongwei, Zhang, Jin, Li, Jian, Liu, Qian, Sun, Zhongsheng, Zhong, Jianing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8592569/
https://www.ncbi.nlm.nih.gov/pubmed/34738906
http://dx.doi.org/10.7554/eLife.70672
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author Zhang, Chunbo
Zhong, Tianyu
Li, Yuanyuan
Li, Xianfeng
Yuan, Xiaopeng
Liu, Linlin
Wu, Weilin
Wu, Jing
Wu, Ye
Liang, Rui
Xie, Xinhua
Kang, Chuanchuan
Liu, Yuwen
Lai, Zhonghong
Xiao, Jianbo
Tang, Zhixian
Jin, Riqun
Wang, Yan
Xiao, Yongwei
Zhang, Jin
Li, Jian
Liu, Qian
Sun, Zhongsheng
Zhong, Jianing
author_facet Zhang, Chunbo
Zhong, Tianyu
Li, Yuanyuan
Li, Xianfeng
Yuan, Xiaopeng
Liu, Linlin
Wu, Weilin
Wu, Jing
Wu, Ye
Liang, Rui
Xie, Xinhua
Kang, Chuanchuan
Liu, Yuwen
Lai, Zhonghong
Xiao, Jianbo
Tang, Zhixian
Jin, Riqun
Wang, Yan
Xiao, Yongwei
Zhang, Jin
Li, Jian
Liu, Qian
Sun, Zhongsheng
Zhong, Jianing
author_sort Zhang, Chunbo
collection PubMed
description Ten-eleven translocation methylcytosine dioxygenase 1 (TET1) is involved in multiple biological functions in cell development, differentiation, and transcriptional regulation. Tet1 deficient mice display the defects of murine glucose metabolism. However, the role of TET1 in metabolic homeostasis keeps unknown. Here, our finding demonstrates that hepatic TET1 physically interacts with silent information regulator T1 (SIRT1) via its C-terminal and activates its deacetylase activity, further regulating the acetylation-dependent cellular translocalization of transcriptional factors PGC-1α and FOXO1, resulting in the activation of hepatic gluconeogenic gene expression that includes PPARGC1A, G6PC, and SLC2A4. Importantly, the hepatic gluconeogenic gene activation program induced by fasting is inhibited in Tet1 heterozygous mice livers. The adenosine 5’-monophosphate-activated protein kinase (AMPK) activators metformin or AICAR—two compounds that mimic fasting—elevate hepatic gluconeogenic gene expression dependent on in turn activation of the AMPK-TET1-SIRT1 axis. Collectively, our study identifies TET1 as a SIRT1 coactivator and demonstrates that the AMPK-TET1-SIRT1 axis represents a potential mechanism or therapeutic target for glucose metabolism or metabolic diseases.
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spelling pubmed-85925692021-11-17 The hepatic AMPK-TET1-SIRT1 axis regulates glucose homeostasis Zhang, Chunbo Zhong, Tianyu Li, Yuanyuan Li, Xianfeng Yuan, Xiaopeng Liu, Linlin Wu, Weilin Wu, Jing Wu, Ye Liang, Rui Xie, Xinhua Kang, Chuanchuan Liu, Yuwen Lai, Zhonghong Xiao, Jianbo Tang, Zhixian Jin, Riqun Wang, Yan Xiao, Yongwei Zhang, Jin Li, Jian Liu, Qian Sun, Zhongsheng Zhong, Jianing eLife Biochemistry and Chemical Biology Ten-eleven translocation methylcytosine dioxygenase 1 (TET1) is involved in multiple biological functions in cell development, differentiation, and transcriptional regulation. Tet1 deficient mice display the defects of murine glucose metabolism. However, the role of TET1 in metabolic homeostasis keeps unknown. Here, our finding demonstrates that hepatic TET1 physically interacts with silent information regulator T1 (SIRT1) via its C-terminal and activates its deacetylase activity, further regulating the acetylation-dependent cellular translocalization of transcriptional factors PGC-1α and FOXO1, resulting in the activation of hepatic gluconeogenic gene expression that includes PPARGC1A, G6PC, and SLC2A4. Importantly, the hepatic gluconeogenic gene activation program induced by fasting is inhibited in Tet1 heterozygous mice livers. The adenosine 5’-monophosphate-activated protein kinase (AMPK) activators metformin or AICAR—two compounds that mimic fasting—elevate hepatic gluconeogenic gene expression dependent on in turn activation of the AMPK-TET1-SIRT1 axis. Collectively, our study identifies TET1 as a SIRT1 coactivator and demonstrates that the AMPK-TET1-SIRT1 axis represents a potential mechanism or therapeutic target for glucose metabolism or metabolic diseases. eLife Sciences Publications, Ltd 2021-11-05 /pmc/articles/PMC8592569/ /pubmed/34738906 http://dx.doi.org/10.7554/eLife.70672 Text en © 2021, Zhang et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Biochemistry and Chemical Biology
Zhang, Chunbo
Zhong, Tianyu
Li, Yuanyuan
Li, Xianfeng
Yuan, Xiaopeng
Liu, Linlin
Wu, Weilin
Wu, Jing
Wu, Ye
Liang, Rui
Xie, Xinhua
Kang, Chuanchuan
Liu, Yuwen
Lai, Zhonghong
Xiao, Jianbo
Tang, Zhixian
Jin, Riqun
Wang, Yan
Xiao, Yongwei
Zhang, Jin
Li, Jian
Liu, Qian
Sun, Zhongsheng
Zhong, Jianing
The hepatic AMPK-TET1-SIRT1 axis regulates glucose homeostasis
title The hepatic AMPK-TET1-SIRT1 axis regulates glucose homeostasis
title_full The hepatic AMPK-TET1-SIRT1 axis regulates glucose homeostasis
title_fullStr The hepatic AMPK-TET1-SIRT1 axis regulates glucose homeostasis
title_full_unstemmed The hepatic AMPK-TET1-SIRT1 axis regulates glucose homeostasis
title_short The hepatic AMPK-TET1-SIRT1 axis regulates glucose homeostasis
title_sort hepatic ampk-tet1-sirt1 axis regulates glucose homeostasis
topic Biochemistry and Chemical Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8592569/
https://www.ncbi.nlm.nih.gov/pubmed/34738906
http://dx.doi.org/10.7554/eLife.70672
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