Acute Deletion of the Glucocorticoid Receptor in Hepatocytes Disrupts Postprandial Lipid Metabolism in Male Mice

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Acute Deletion of the Glucocorticoid Receptor in Hepatocytes Disrupts Postprandial Lipid Metabolism in Male Mice. / Correia, Catarina Mendes; Præstholm, Stine Marie; Havelund, Jesper Foged; Pedersen, Felix Boel; Siersbæk, Majken Storm; Ebbesen, Morten Frendø; Gerhart-Hines, Zach; Heeren, Joerg; Brewer, Jonathan; Larsen, Steen; Blagoev, Blagoy; Færgeman, Nils Joakim; Grøntved, Lars.

In: Endocrinology, Vol. 164, No. 10, 164, 2023, p. 1-17.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Correia, CM, Præstholm, SM, Havelund, JF, Pedersen, FB, Siersbæk, MS, Ebbesen, MF, Gerhart-Hines, Z, Heeren, J, Brewer, J, Larsen, S, Blagoev, B, Færgeman, NJ & Grøntved, L 2023, 'Acute Deletion of the Glucocorticoid Receptor in Hepatocytes Disrupts Postprandial Lipid Metabolism in Male Mice', Endocrinology, vol. 164, no. 10, 164, pp. 1-17. https://doi.org/10.1210/endocr/bqad128

APA

Correia, C. M., Præstholm, S. M., Havelund, J. F., Pedersen, F. B., Siersbæk, M. S., Ebbesen, M. F., Gerhart-Hines, Z., Heeren, J., Brewer, J., Larsen, S., Blagoev, B., Færgeman, N. J., & Grøntved, L. (2023). Acute Deletion of the Glucocorticoid Receptor in Hepatocytes Disrupts Postprandial Lipid Metabolism in Male Mice. Endocrinology, 164(10), 1-17. [164]. https://doi.org/10.1210/endocr/bqad128

Vancouver

Correia CM, Præstholm SM, Havelund JF, Pedersen FB, Siersbæk MS, Ebbesen MF et al. Acute Deletion of the Glucocorticoid Receptor in Hepatocytes Disrupts Postprandial Lipid Metabolism in Male Mice. Endocrinology. 2023;164(10):1-17. 164. https://doi.org/10.1210/endocr/bqad128

Author

Correia, Catarina Mendes ; Præstholm, Stine Marie ; Havelund, Jesper Foged ; Pedersen, Felix Boel ; Siersbæk, Majken Storm ; Ebbesen, Morten Frendø ; Gerhart-Hines, Zach ; Heeren, Joerg ; Brewer, Jonathan ; Larsen, Steen ; Blagoev, Blagoy ; Færgeman, Nils Joakim ; Grøntved, Lars. / Acute Deletion of the Glucocorticoid Receptor in Hepatocytes Disrupts Postprandial Lipid Metabolism in Male Mice. In: Endocrinology. 2023 ; Vol. 164, No. 10. pp. 1-17.

Bibtex

@article{381dd879fe1f404ebf5f4bd1797a845a,
title = "Acute Deletion of the Glucocorticoid Receptor in Hepatocytes Disrupts Postprandial Lipid Metabolism in Male Mice",
abstract = "Hepatic lipid metabolism is highly dynamic, and disruption of several circadian transcriptional regulators results in hepatic steatosis. This includes genetic disruption of the glucocorticoid receptor (GR) as the liver develops. To address the functional role of GR in the adult liver, we used an acute hepatocyte-specific GR knockout model to study temporal hepatic lipid metabolism governed by GR at several preprandial and postprandial circadian timepoints. Lipidomics analysis revealed significant temporal lipid metabolism, where GR disruption results in impaired regulation of specific triglycerides, nonesterified fatty acids, and sphingolipids. This correlates with increased number and size of lipid droplets and mildly reduced mitochondrial respiration, most noticeably in the postprandial phase. Proteomics and transcriptomics analyses suggest that dysregulated lipid metabolism originates from pronounced induced expression of enzymes involved in fatty acid synthesis, β-oxidation, and sphingolipid metabolism. Integration of GR cistromic data suggests that induced gene expression is a result of regulatory actions secondary to direct GR effects on gene transcription.",
keywords = "Male, Animals, Mice, Lipid Metabolism/genetics, Receptors, Glucocorticoid/genetics, Hepatocytes, Liver, Adipogenesis",
author = "Correia, {Catarina Mendes} and Pr{\ae}stholm, {Stine Marie} and Havelund, {Jesper Foged} and Pedersen, {Felix Boel} and Siersb{\ae}k, {Majken Storm} and Ebbesen, {Morten Frend{\o}} and Zach Gerhart-Hines and Joerg Heeren and Jonathan Brewer and Steen Larsen and Blagoy Blagoev and F{\ae}rgeman, {Nils Joakim} and Lars Gr{\o}ntved",
note = "{\textcopyright} The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.",
year = "2023",
doi = "10.1210/endocr/bqad128",
language = "English",
volume = "164",
pages = "1--17",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0013-7227",
publisher = "Oxford University Press",
number = "10",

}

RIS

TY - JOUR

T1 - Acute Deletion of the Glucocorticoid Receptor in Hepatocytes Disrupts Postprandial Lipid Metabolism in Male Mice

AU - Correia, Catarina Mendes

AU - Præstholm, Stine Marie

AU - Havelund, Jesper Foged

AU - Pedersen, Felix Boel

AU - Siersbæk, Majken Storm

AU - Ebbesen, Morten Frendø

AU - Gerhart-Hines, Zach

AU - Heeren, Joerg

AU - Brewer, Jonathan

AU - Larsen, Steen

AU - Blagoev, Blagoy

AU - Færgeman, Nils Joakim

AU - Grøntved, Lars

N1 - © The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

PY - 2023

Y1 - 2023

N2 - Hepatic lipid metabolism is highly dynamic, and disruption of several circadian transcriptional regulators results in hepatic steatosis. This includes genetic disruption of the glucocorticoid receptor (GR) as the liver develops. To address the functional role of GR in the adult liver, we used an acute hepatocyte-specific GR knockout model to study temporal hepatic lipid metabolism governed by GR at several preprandial and postprandial circadian timepoints. Lipidomics analysis revealed significant temporal lipid metabolism, where GR disruption results in impaired regulation of specific triglycerides, nonesterified fatty acids, and sphingolipids. This correlates with increased number and size of lipid droplets and mildly reduced mitochondrial respiration, most noticeably in the postprandial phase. Proteomics and transcriptomics analyses suggest that dysregulated lipid metabolism originates from pronounced induced expression of enzymes involved in fatty acid synthesis, β-oxidation, and sphingolipid metabolism. Integration of GR cistromic data suggests that induced gene expression is a result of regulatory actions secondary to direct GR effects on gene transcription.

AB - Hepatic lipid metabolism is highly dynamic, and disruption of several circadian transcriptional regulators results in hepatic steatosis. This includes genetic disruption of the glucocorticoid receptor (GR) as the liver develops. To address the functional role of GR in the adult liver, we used an acute hepatocyte-specific GR knockout model to study temporal hepatic lipid metabolism governed by GR at several preprandial and postprandial circadian timepoints. Lipidomics analysis revealed significant temporal lipid metabolism, where GR disruption results in impaired regulation of specific triglycerides, nonesterified fatty acids, and sphingolipids. This correlates with increased number and size of lipid droplets and mildly reduced mitochondrial respiration, most noticeably in the postprandial phase. Proteomics and transcriptomics analyses suggest that dysregulated lipid metabolism originates from pronounced induced expression of enzymes involved in fatty acid synthesis, β-oxidation, and sphingolipid metabolism. Integration of GR cistromic data suggests that induced gene expression is a result of regulatory actions secondary to direct GR effects on gene transcription.

KW - Male

KW - Animals

KW - Mice

KW - Lipid Metabolism/genetics

KW - Receptors, Glucocorticoid/genetics

KW - Hepatocytes

KW - Liver

KW - Adipogenesis

U2 - 10.1210/endocr/bqad128

DO - 10.1210/endocr/bqad128

M3 - Journal article

C2 - 37610219

VL - 164

SP - 1

EP - 17

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0013-7227

IS - 10

M1 - 164

ER -

ID: 367906842