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The hepatic circadian clock fine-tunes the lipogenic response to feeding through RORα/γ
Liver lipid metabolism is under intricate temporal control by both the circadian clock and feeding. The interplay between these two mechanisms is not clear. Here we show that liver-specific depletion of nuclear receptors RORα and RORγ, key components of the molecular circadian clock, up-regulate exp...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5558923/ https://www.ncbi.nlm.nih.gov/pubmed/28747429 http://dx.doi.org/10.1101/gad.302323.117 |
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author | Zhang, Yuxiang Papazyan, Romeo Damle, Manashree Fang, Bin Jager, Jennifer Feng, Dan Peed, Lindsey C. Guan, Dongyin Sun, Zheng Lazar, Mitchell A. |
author_facet | Zhang, Yuxiang Papazyan, Romeo Damle, Manashree Fang, Bin Jager, Jennifer Feng, Dan Peed, Lindsey C. Guan, Dongyin Sun, Zheng Lazar, Mitchell A. |
author_sort | Zhang, Yuxiang |
collection | PubMed |
description | Liver lipid metabolism is under intricate temporal control by both the circadian clock and feeding. The interplay between these two mechanisms is not clear. Here we show that liver-specific depletion of nuclear receptors RORα and RORγ, key components of the molecular circadian clock, up-regulate expression of lipogenic genes only under fed conditions at Zeitgeber time 22 (ZT22) but not under fasting conditions at ZT22 or ad libitum conditions at ZT10. RORα/γ controls circadian expression of Insig2, which keeps feeding-induced SREBP1c activation under check. Loss of RORα/γ causes overactivation of the SREBP-dependent lipogenic response to feeding, exacerbating diet-induced hepatic steatosis. These findings thus establish ROR/INSIG2/SREBP as a molecular pathway by which circadian clock components anticipatorily regulate lipogenic responses to feeding. This highlights the importance of time of day as a consideration in the treatment of liver metabolic disorders. |
format | Online Article Text |
id | pubmed-5558923 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-55589232017-12-15 The hepatic circadian clock fine-tunes the lipogenic response to feeding through RORα/γ Zhang, Yuxiang Papazyan, Romeo Damle, Manashree Fang, Bin Jager, Jennifer Feng, Dan Peed, Lindsey C. Guan, Dongyin Sun, Zheng Lazar, Mitchell A. Genes Dev Research Papers Liver lipid metabolism is under intricate temporal control by both the circadian clock and feeding. The interplay between these two mechanisms is not clear. Here we show that liver-specific depletion of nuclear receptors RORα and RORγ, key components of the molecular circadian clock, up-regulate expression of lipogenic genes only under fed conditions at Zeitgeber time 22 (ZT22) but not under fasting conditions at ZT22 or ad libitum conditions at ZT10. RORα/γ controls circadian expression of Insig2, which keeps feeding-induced SREBP1c activation under check. Loss of RORα/γ causes overactivation of the SREBP-dependent lipogenic response to feeding, exacerbating diet-induced hepatic steatosis. These findings thus establish ROR/INSIG2/SREBP as a molecular pathway by which circadian clock components anticipatorily regulate lipogenic responses to feeding. This highlights the importance of time of day as a consideration in the treatment of liver metabolic disorders. Cold Spring Harbor Laboratory Press 2017-06-15 /pmc/articles/PMC5558923/ /pubmed/28747429 http://dx.doi.org/10.1101/gad.302323.117 Text en © 2017 Zhang et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/. |
spellingShingle | Research Papers Zhang, Yuxiang Papazyan, Romeo Damle, Manashree Fang, Bin Jager, Jennifer Feng, Dan Peed, Lindsey C. Guan, Dongyin Sun, Zheng Lazar, Mitchell A. The hepatic circadian clock fine-tunes the lipogenic response to feeding through RORα/γ |
title | The hepatic circadian clock fine-tunes the lipogenic response to feeding through RORα/γ |
title_full | The hepatic circadian clock fine-tunes the lipogenic response to feeding through RORα/γ |
title_fullStr | The hepatic circadian clock fine-tunes the lipogenic response to feeding through RORα/γ |
title_full_unstemmed | The hepatic circadian clock fine-tunes the lipogenic response to feeding through RORα/γ |
title_short | The hepatic circadian clock fine-tunes the lipogenic response to feeding through RORα/γ |
title_sort | hepatic circadian clock fine-tunes the lipogenic response to feeding through rorα/γ |
topic | Research Papers |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5558923/ https://www.ncbi.nlm.nih.gov/pubmed/28747429 http://dx.doi.org/10.1101/gad.302323.117 |
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