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Insulin post-transcriptionally modulates Bmal1 protein to affect the hepatic circadian clock
Although food availability is a potent synchronizer of the peripheral circadian clock in mammals, the underlying mechanisms are unclear. Here, we show that hepatic Bmal1, a core transcription activator of the molecular clock, is post-transcriptionally regulated by signals from insulin, an important...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5013695/ https://www.ncbi.nlm.nih.gov/pubmed/27576939 http://dx.doi.org/10.1038/ncomms12696 |
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author | Dang, Fabin Sun, Xiujie Ma, Xiang Wu, Rong Zhang, Deyi Chen, Yaqiong Xu, Qian Wu, Yuting Liu, Yi |
author_facet | Dang, Fabin Sun, Xiujie Ma, Xiang Wu, Rong Zhang, Deyi Chen, Yaqiong Xu, Qian Wu, Yuting Liu, Yi |
author_sort | Dang, Fabin |
collection | PubMed |
description | Although food availability is a potent synchronizer of the peripheral circadian clock in mammals, the underlying mechanisms are unclear. Here, we show that hepatic Bmal1, a core transcription activator of the molecular clock, is post-transcriptionally regulated by signals from insulin, an important hormone that is temporally controlled by feeding. Insulin promotes postprandial Akt-mediated Ser42-phosphorylation of Bmal1 to induce its dissociation from DNA, interaction with 14-3-3 protein and subsequently nuclear exclusion, which results in the suppression of Bmal1 transcriptional activity. Inverted feeding cycles not only shift the phase of daily insulin oscillation, but also elevate the amplitude due to food overconsumption. This enhanced and reversed insulin signalling initiates the reset of clock gene rhythms by altering Bmal1 nuclear accumulation in mouse liver. These results reveal the molecular mechanism of insulin signalling in regulating peripheral circadian rhythms. |
format | Online Article Text |
id | pubmed-5013695 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-50136952016-09-20 Insulin post-transcriptionally modulates Bmal1 protein to affect the hepatic circadian clock Dang, Fabin Sun, Xiujie Ma, Xiang Wu, Rong Zhang, Deyi Chen, Yaqiong Xu, Qian Wu, Yuting Liu, Yi Nat Commun Article Although food availability is a potent synchronizer of the peripheral circadian clock in mammals, the underlying mechanisms are unclear. Here, we show that hepatic Bmal1, a core transcription activator of the molecular clock, is post-transcriptionally regulated by signals from insulin, an important hormone that is temporally controlled by feeding. Insulin promotes postprandial Akt-mediated Ser42-phosphorylation of Bmal1 to induce its dissociation from DNA, interaction with 14-3-3 protein and subsequently nuclear exclusion, which results in the suppression of Bmal1 transcriptional activity. Inverted feeding cycles not only shift the phase of daily insulin oscillation, but also elevate the amplitude due to food overconsumption. This enhanced and reversed insulin signalling initiates the reset of clock gene rhythms by altering Bmal1 nuclear accumulation in mouse liver. These results reveal the molecular mechanism of insulin signalling in regulating peripheral circadian rhythms. Nature Publishing Group 2016-08-31 /pmc/articles/PMC5013695/ /pubmed/27576939 http://dx.doi.org/10.1038/ncomms12696 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Dang, Fabin Sun, Xiujie Ma, Xiang Wu, Rong Zhang, Deyi Chen, Yaqiong Xu, Qian Wu, Yuting Liu, Yi Insulin post-transcriptionally modulates Bmal1 protein to affect the hepatic circadian clock |
title | Insulin post-transcriptionally modulates Bmal1 protein to affect the hepatic circadian clock |
title_full | Insulin post-transcriptionally modulates Bmal1 protein to affect the hepatic circadian clock |
title_fullStr | Insulin post-transcriptionally modulates Bmal1 protein to affect the hepatic circadian clock |
title_full_unstemmed | Insulin post-transcriptionally modulates Bmal1 protein to affect the hepatic circadian clock |
title_short | Insulin post-transcriptionally modulates Bmal1 protein to affect the hepatic circadian clock |
title_sort | insulin post-transcriptionally modulates bmal1 protein to affect the hepatic circadian clock |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5013695/ https://www.ncbi.nlm.nih.gov/pubmed/27576939 http://dx.doi.org/10.1038/ncomms12696 |
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