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TAZ inhibits glucocorticoid receptor and coordinates hepatic glucose homeostasis in normal physiological states

The elucidation of the mechanisms whereby the liver maintains glucose homeostasis is crucial for the understanding of physiological and pathological states. Here, we show a novel role of hepatic transcriptional co-activator with PDZ-binding motif (TAZ) in the inhibition of glucocorticoid receptor (G...

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Autores principales: Xu, Simiao, Liu, Yangyang, Hu, Ruixiang, Wang, Min, Stöhr, Oliver, Xiong, Yibo, Chen, Liang, Kang, Hong, Zheng, Lingyun, Cai, Songjie, He, Li, Wang, Cunchuan, Copps, Kyle D, White, Morris F, Miao, Ji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8555985/
https://www.ncbi.nlm.nih.gov/pubmed/34622775
http://dx.doi.org/10.7554/eLife.57462
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author Xu, Simiao
Liu, Yangyang
Hu, Ruixiang
Wang, Min
Stöhr, Oliver
Xiong, Yibo
Chen, Liang
Kang, Hong
Zheng, Lingyun
Cai, Songjie
He, Li
Wang, Cunchuan
Copps, Kyle D
White, Morris F
Miao, Ji
author_facet Xu, Simiao
Liu, Yangyang
Hu, Ruixiang
Wang, Min
Stöhr, Oliver
Xiong, Yibo
Chen, Liang
Kang, Hong
Zheng, Lingyun
Cai, Songjie
He, Li
Wang, Cunchuan
Copps, Kyle D
White, Morris F
Miao, Ji
author_sort Xu, Simiao
collection PubMed
description The elucidation of the mechanisms whereby the liver maintains glucose homeostasis is crucial for the understanding of physiological and pathological states. Here, we show a novel role of hepatic transcriptional co-activator with PDZ-binding motif (TAZ) in the inhibition of glucocorticoid receptor (GR). TAZ is abundantly expressed in pericentral hepatocytes and its expression is markedly reduced by fasting. TAZ interacts via its WW domain with the ligand-binding domain of GR to limit the binding of GR to the GR response element in gluconeogenic gene promoters. Therefore, liver-specific TAZ knockout mice show increases in glucose production and blood glucose concentration. Conversely, the overexpression of TAZ in mouse liver reduces the binding of GR to gluconeogenic gene promoters and glucose production. Thus, our findings demonstrate that hepatic TAZ inhibits GR transactivation of gluconeogenic genes and coordinates gluconeogenesis in response to physiological fasting and feeding.
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spelling pubmed-85559852021-11-01 TAZ inhibits glucocorticoid receptor and coordinates hepatic glucose homeostasis in normal physiological states Xu, Simiao Liu, Yangyang Hu, Ruixiang Wang, Min Stöhr, Oliver Xiong, Yibo Chen, Liang Kang, Hong Zheng, Lingyun Cai, Songjie He, Li Wang, Cunchuan Copps, Kyle D White, Morris F Miao, Ji eLife Biochemistry and Chemical Biology The elucidation of the mechanisms whereby the liver maintains glucose homeostasis is crucial for the understanding of physiological and pathological states. Here, we show a novel role of hepatic transcriptional co-activator with PDZ-binding motif (TAZ) in the inhibition of glucocorticoid receptor (GR). TAZ is abundantly expressed in pericentral hepatocytes and its expression is markedly reduced by fasting. TAZ interacts via its WW domain with the ligand-binding domain of GR to limit the binding of GR to the GR response element in gluconeogenic gene promoters. Therefore, liver-specific TAZ knockout mice show increases in glucose production and blood glucose concentration. Conversely, the overexpression of TAZ in mouse liver reduces the binding of GR to gluconeogenic gene promoters and glucose production. Thus, our findings demonstrate that hepatic TAZ inhibits GR transactivation of gluconeogenic genes and coordinates gluconeogenesis in response to physiological fasting and feeding. eLife Sciences Publications, Ltd 2021-10-08 /pmc/articles/PMC8555985/ /pubmed/34622775 http://dx.doi.org/10.7554/eLife.57462 Text en © 2021, Xu 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
Xu, Simiao
Liu, Yangyang
Hu, Ruixiang
Wang, Min
Stöhr, Oliver
Xiong, Yibo
Chen, Liang
Kang, Hong
Zheng, Lingyun
Cai, Songjie
He, Li
Wang, Cunchuan
Copps, Kyle D
White, Morris F
Miao, Ji
TAZ inhibits glucocorticoid receptor and coordinates hepatic glucose homeostasis in normal physiological states
title TAZ inhibits glucocorticoid receptor and coordinates hepatic glucose homeostasis in normal physiological states
title_full TAZ inhibits glucocorticoid receptor and coordinates hepatic glucose homeostasis in normal physiological states
title_fullStr TAZ inhibits glucocorticoid receptor and coordinates hepatic glucose homeostasis in normal physiological states
title_full_unstemmed TAZ inhibits glucocorticoid receptor and coordinates hepatic glucose homeostasis in normal physiological states
title_short TAZ inhibits glucocorticoid receptor and coordinates hepatic glucose homeostasis in normal physiological states
title_sort taz inhibits glucocorticoid receptor and coordinates hepatic glucose homeostasis in normal physiological states
topic Biochemistry and Chemical Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8555985/
https://www.ncbi.nlm.nih.gov/pubmed/34622775
http://dx.doi.org/10.7554/eLife.57462
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