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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2021
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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. |
format | Online Article Text |
id | pubmed-8592569 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
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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