Impaired glucocorticoid receptor expression in liver disrupts feeding-induced gene expression, glucose uptake, and glycogen storage

Summary: The transition from a fasted to a fed state is associated with extensive transcriptional remodeling in hepatocytes facilitated by hormonal- and nutritional-regulated transcription factors. Here, we use a liver-specific glucocorticoid receptor (GR) knockout (L-GRKO) model to investigate the...

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Autores principales:	Stine M. Præstholm, Catarina M. Correia, Victor E. Goitea, Majken S. Siersbæk, Mathilde Jørgensen, Jesper F. Havelund, Thomas Å. Pedersen, Nils J. Færgeman, Lars Grøntved
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	glucocorticoid receptor liver Gck temporal gene expression feeding Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/830a919b1e394d2a9c82955554f4eaec
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spelling	oai:doaj.org-article:830a919b1e394d2a9c82955554f4eaec2021-11-04T04:29:26ZImpaired glucocorticoid receptor expression in liver disrupts feeding-induced gene expression, glucose uptake, and glycogen storage2211-124710.1016/j.celrep.2021.109938https://doaj.org/article/830a919b1e394d2a9c82955554f4eaec2021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S221112472101411Xhttps://doaj.org/toc/2211-1247Summary: The transition from a fasted to a fed state is associated with extensive transcriptional remodeling in hepatocytes facilitated by hormonal- and nutritional-regulated transcription factors. Here, we use a liver-specific glucocorticoid receptor (GR) knockout (L-GRKO) model to investigate the temporal hepatic expression of GR target genes in response to feeding. Interestingly, in addition to the well-described fasting-regulated genes, we identify a subset of hepatic feeding-induced genes that requires GR for full expression. This includes Gck, which is important for hepatic glucose uptake, utilization, and storage. We show that insulin and glucocorticoids cooperatively regulate hepatic Gck expression in a direct GR-dependent manner by a 4.6 kb upstream GR binding site operating as a Gck enhancer. L-GRKO blunts preprandial and early postprandial Gck expression, which ultimately affects early postprandial hepatic glucose uptake, phosphorylation, and glycogen storage. Thus, GR is positively involved in feeding-induced gene expression and important for postprandial glucose metabolism in the liver.Stine M. PræstholmCatarina M. CorreiaVictor E. GoiteaMajken S. SiersbækMathilde JørgensenJesper F. HavelundThomas Å. PedersenNils J. FærgemanLars GrøntvedElsevierarticleglucocorticoid receptorliverGcktemporalgene expressionfeedingBiology (General)QH301-705.5ENCell Reports, Vol 37, Iss 5, Pp 109938- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	glucocorticoid receptor liver Gck temporal gene expression feeding Biology (General) QH301-705.5
spellingShingle	glucocorticoid receptor liver Gck temporal gene expression feeding Biology (General) QH301-705.5 Stine M. Præstholm Catarina M. Correia Victor E. Goitea Majken S. Siersbæk Mathilde Jørgensen Jesper F. Havelund Thomas Å. Pedersen Nils J. Færgeman Lars Grøntved Impaired glucocorticoid receptor expression in liver disrupts feeding-induced gene expression, glucose uptake, and glycogen storage
description	Summary: The transition from a fasted to a fed state is associated with extensive transcriptional remodeling in hepatocytes facilitated by hormonal- and nutritional-regulated transcription factors. Here, we use a liver-specific glucocorticoid receptor (GR) knockout (L-GRKO) model to investigate the temporal hepatic expression of GR target genes in response to feeding. Interestingly, in addition to the well-described fasting-regulated genes, we identify a subset of hepatic feeding-induced genes that requires GR for full expression. This includes Gck, which is important for hepatic glucose uptake, utilization, and storage. We show that insulin and glucocorticoids cooperatively regulate hepatic Gck expression in a direct GR-dependent manner by a 4.6 kb upstream GR binding site operating as a Gck enhancer. L-GRKO blunts preprandial and early postprandial Gck expression, which ultimately affects early postprandial hepatic glucose uptake, phosphorylation, and glycogen storage. Thus, GR is positively involved in feeding-induced gene expression and important for postprandial glucose metabolism in the liver.
format	article
author	Stine M. Præstholm Catarina M. Correia Victor E. Goitea Majken S. Siersbæk Mathilde Jørgensen Jesper F. Havelund Thomas Å. Pedersen Nils J. Færgeman Lars Grøntved
author_facet	Stine M. Præstholm Catarina M. Correia Victor E. Goitea Majken S. Siersbæk Mathilde Jørgensen Jesper F. Havelund Thomas Å. Pedersen Nils J. Færgeman Lars Grøntved
author_sort	Stine M. Præstholm
title	Impaired glucocorticoid receptor expression in liver disrupts feeding-induced gene expression, glucose uptake, and glycogen storage
title_short	Impaired glucocorticoid receptor expression in liver disrupts feeding-induced gene expression, glucose uptake, and glycogen storage
title_full	Impaired glucocorticoid receptor expression in liver disrupts feeding-induced gene expression, glucose uptake, and glycogen storage
title_fullStr	Impaired glucocorticoid receptor expression in liver disrupts feeding-induced gene expression, glucose uptake, and glycogen storage
title_full_unstemmed	Impaired glucocorticoid receptor expression in liver disrupts feeding-induced gene expression, glucose uptake, and glycogen storage
title_sort	impaired glucocorticoid receptor expression in liver disrupts feeding-induced gene expression, glucose uptake, and glycogen storage
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/830a919b1e394d2a9c82955554f4eaec
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Impaired glucocorticoid receptor expression in liver disrupts feeding-induced gene expression, glucose uptake, and glycogen storage

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