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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Chunbo Zhang, Tianyu Zhong, Yuanyuan Li, Xianfeng Li, Xiaopeng Yuan, Linlin Liu, Weilin Wu, Jing Wu, Ye Wu, Rui Liang, Xinhua Xie, Chuanchuan Kang, Yuwen Liu, Zhonghong Lai, Jianbo Xiao, Zhixian Tang, Riqun Jin, Yan Wang, Yongwei Xiao, Jin Zhang, Jian Li, Qian Liu, Zhongsheng Sun, Jianing Zhong
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	TET1 SIRT1 acetylation modification transcriptional regulation glucose metabolism Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/774d46896e9b4a30b917a9ad9a0cec1d
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:774d46896e9b4a30b917a9ad9a0cec1d
record_format	dspace
spelling	oai:doaj.org-article:774d46896e9b4a30b917a9ad9a0cec1d2021-11-19T12:17:50ZThe hepatic AMPK-TET1-SIRT1 axis regulates glucose homeostasis10.7554/eLife.706722050-084Xe70672https://doaj.org/article/774d46896e9b4a30b917a9ad9a0cec1d2021-11-01T00:00:00Zhttps://elifesciences.org/articles/70672https://doaj.org/toc/2050-084XTen-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.Chunbo ZhangTianyu ZhongYuanyuan LiXianfeng LiXiaopeng YuanLinlin LiuWeilin WuJing WuYe WuRui LiangXinhua XieChuanchuan KangYuwen LiuZhonghong LaiJianbo XiaoZhixian TangRiqun JinYan WangYongwei XiaoJin ZhangJian LiQian LiuZhongsheng SunJianing ZhongeLife Sciences Publications LtdarticleTET1SIRT1acetylation modificationtranscriptional regulationglucose metabolismMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	TET1 SIRT1 acetylation modification transcriptional regulation glucose metabolism Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	TET1 SIRT1 acetylation modification transcriptional regulation glucose metabolism Medicine R Science Q Biology (General) QH301-705.5 Chunbo Zhang Tianyu Zhong Yuanyuan Li Xianfeng Li Xiaopeng Yuan Linlin Liu Weilin Wu Jing Wu Ye Wu Rui Liang Xinhua Xie Chuanchuan Kang Yuwen Liu Zhonghong Lai Jianbo Xiao Zhixian Tang Riqun Jin Yan Wang Yongwei Xiao Jin Zhang Jian Li Qian Liu Zhongsheng Sun Jianing Zhong The hepatic AMPK-TET1-SIRT1 axis regulates glucose homeostasis
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	article
author	Chunbo Zhang Tianyu Zhong Yuanyuan Li Xianfeng Li Xiaopeng Yuan Linlin Liu Weilin Wu Jing Wu Ye Wu Rui Liang Xinhua Xie Chuanchuan Kang Yuwen Liu Zhonghong Lai Jianbo Xiao Zhixian Tang Riqun Jin Yan Wang Yongwei Xiao Jin Zhang Jian Li Qian Liu Zhongsheng Sun Jianing Zhong
author_facet	Chunbo Zhang Tianyu Zhong Yuanyuan Li Xianfeng Li Xiaopeng Yuan Linlin Liu Weilin Wu Jing Wu Ye Wu Rui Liang Xinhua Xie Chuanchuan Kang Yuwen Liu Zhonghong Lai Jianbo Xiao Zhixian Tang Riqun Jin Yan Wang Yongwei Xiao Jin Zhang Jian Li Qian Liu Zhongsheng Sun Jianing Zhong
author_sort	Chunbo Zhang
title	The hepatic AMPK-TET1-SIRT1 axis regulates glucose homeostasis
title_short	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_sort	hepatic ampk-tet1-sirt1 axis regulates glucose homeostasis
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/774d46896e9b4a30b917a9ad9a0cec1d
work_keys_str_mv	AT chunbozhang thehepaticampktet1sirt1axisregulatesglucosehomeostasis AT tianyuzhong thehepaticampktet1sirt1axisregulatesglucosehomeostasis AT yuanyuanli thehepaticampktet1sirt1axisregulatesglucosehomeostasis AT xianfengli thehepaticampktet1sirt1axisregulatesglucosehomeostasis AT xiaopengyuan thehepaticampktet1sirt1axisregulatesglucosehomeostasis AT linlinliu thehepaticampktet1sirt1axisregulatesglucosehomeostasis AT weilinwu thehepaticampktet1sirt1axisregulatesglucosehomeostasis AT jingwu thehepaticampktet1sirt1axisregulatesglucosehomeostasis AT yewu thehepaticampktet1sirt1axisregulatesglucosehomeostasis AT ruiliang thehepaticampktet1sirt1axisregulatesglucosehomeostasis AT xinhuaxie thehepaticampktet1sirt1axisregulatesglucosehomeostasis AT chuanchuankang thehepaticampktet1sirt1axisregulatesglucosehomeostasis AT yuwenliu thehepaticampktet1sirt1axisregulatesglucosehomeostasis AT zhonghonglai thehepaticampktet1sirt1axisregulatesglucosehomeostasis AT jianboxiao thehepaticampktet1sirt1axisregulatesglucosehomeostasis AT zhixiantang thehepaticampktet1sirt1axisregulatesglucosehomeostasis AT riqunjin thehepaticampktet1sirt1axisregulatesglucosehomeostasis AT yanwang thehepaticampktet1sirt1axisregulatesglucosehomeostasis AT yongweixiao thehepaticampktet1sirt1axisregulatesglucosehomeostasis AT jinzhang thehepaticampktet1sirt1axisregulatesglucosehomeostasis AT jianli thehepaticampktet1sirt1axisregulatesglucosehomeostasis AT qianliu thehepaticampktet1sirt1axisregulatesglucosehomeostasis AT zhongshengsun thehepaticampktet1sirt1axisregulatesglucosehomeostasis AT jianingzhong thehepaticampktet1sirt1axisregulatesglucosehomeostasis AT chunbozhang hepaticampktet1sirt1axisregulatesglucosehomeostasis AT tianyuzhong hepaticampktet1sirt1axisregulatesglucosehomeostasis AT yuanyuanli hepaticampktet1sirt1axisregulatesglucosehomeostasis AT xianfengli hepaticampktet1sirt1axisregulatesglucosehomeostasis AT xiaopengyuan hepaticampktet1sirt1axisregulatesglucosehomeostasis AT linlinliu hepaticampktet1sirt1axisregulatesglucosehomeostasis AT weilinwu hepaticampktet1sirt1axisregulatesglucosehomeostasis AT jingwu hepaticampktet1sirt1axisregulatesglucosehomeostasis AT yewu hepaticampktet1sirt1axisregulatesglucosehomeostasis AT ruiliang hepaticampktet1sirt1axisregulatesglucosehomeostasis AT xinhuaxie hepaticampktet1sirt1axisregulatesglucosehomeostasis AT chuanchuankang hepaticampktet1sirt1axisregulatesglucosehomeostasis AT yuwenliu hepaticampktet1sirt1axisregulatesglucosehomeostasis AT zhonghonglai hepaticampktet1sirt1axisregulatesglucosehomeostasis AT jianboxiao hepaticampktet1sirt1axisregulatesglucosehomeostasis AT zhixiantang hepaticampktet1sirt1axisregulatesglucosehomeostasis AT riqunjin hepaticampktet1sirt1axisregulatesglucosehomeostasis AT yanwang hepaticampktet1sirt1axisregulatesglucosehomeostasis AT yongweixiao hepaticampktet1sirt1axisregulatesglucosehomeostasis AT jinzhang hepaticampktet1sirt1axisregulatesglucosehomeostasis AT jianli hepaticampktet1sirt1axisregulatesglucosehomeostasis AT qianliu hepaticampktet1sirt1axisregulatesglucosehomeostasis AT zhongshengsun hepaticampktet1sirt1axisregulatesglucosehomeostasis AT jianingzhong hepaticampktet1sirt1axisregulatesglucosehomeostasis
_version_	1718420075888771072

The hepatic AMPK-TET1-SIRT1 axis regulates glucose homeostasis

Ejemplares similares