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...

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Main Authors:	Dang, Fabin, Sun, Xiujie, Ma, Xiang, Wu, Rong, Zhang, Deyi, Chen, Yaqiong, Xu, Qian, Wu, Yuting, Liu, Yi
Format:	Online
Language:	English
Published:	Nature Publishing Group 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5013695/

id	pubmed-5013695
recordtype	oai_dc
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 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/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Dang, Fabin Sun, Xiujie Ma, Xiang Wu, Rong Zhang, Deyi Chen, Yaqiong Xu, Qian Wu, Yuting Liu, Yi
spellingShingle	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
author_facet	Dang, Fabin Sun, Xiujie Ma, Xiang Wu, Rong Zhang, Deyi Chen, Yaqiong Xu, Qian Wu, Yuting Liu, Yi
author_sort	Dang, Fabin
title	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_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_sort	insulin post-transcriptionally modulates bmal1 protein to affect the hepatic circadian clock
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.
publisher	Nature Publishing Group
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5013695/
_version_	1613645171978665984

Insulin post-transcriptionally modulates Bmal1 protein to affect the hepatic circadian clock

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