Dataset Information

Acute deletion of the glucocorticoid receptor in hepatocytes disrupts postprandial lipid metabolism

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 (hepGRKO) to study temporal hepatic lipid metabolism governed by GR at several pre- and postprandial timepoints. Lipidomics analysis revealed significant temporal lipid metabolism, with GR disruption resulting in impaired regulation of specific triglycerides, non-esterified fatty acids, and sphingolipids. This correlated 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, -oxidation, and sphingolipid metabolism. Integration of GR cistromic data suggests that induced genes are a result of regulatory actions secondary to direct GR effects on transcription.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Liver

SUBMITTER: Felix Boel Pedersen

LAB HEAD: Blagoy Blagoev

PROVIDER: PXD041168 | Pride | 2023-09-07

REPOSITORIES: Pride

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Publications

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

Correia Catarina Mendes CM Præstholm Stine Marie SM Havelund Jesper Foged JF Pedersen Felix Boel FB Siersbæk Majken Storm MS Ebbesen Morten Frendø MF Gerhart-Hines Zach Z Heeren Joerg J Brewer Jonathan J Larsen Steen S Blagoev Blagoy B Færgeman Nils Joakim NJ Grøntved Lars L

Endocrinology 20230801 10

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 significan ...[more]

PMID: 37610219

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Dataset Information

Acute deletion of the glucocorticoid receptor in hepatocytes disrupts postprandial lipid metabolism

Publications

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

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