Correia 2023 Endocrinology
| 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. https://doi.org/10.1210/endocr/bqad128 |
» Endocrinology 164:bqad128. PMID: 37610219
Correia Catarina Mendes, Praestholm Stine Marie, Havelund Jesper Foged, Pedersen Felix Boel, Siersbaek Majken Storm, Ebbesen Morten Frendoe, Gerhart-Hines Zach, Heeren Joerg, Brewer Jonathan, Larsen Steen, Blagoev Blagoy, Faergeman Nils Joakim, Groentved Lars (2023) Endocrinology
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 circadian 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, β-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 gene transcription. • Keywords: Glucocorticoid receptor, Gene expression, Lipid metabolism, Liver • Bioblast editor: Plangger M • O2k-Network Lab: DK Copenhagen Gerhart-Hines Z, DK Copenhagen Larsen S
Labels: MiParea: Respiration, Genetic knockout;overexpression
Organism: Mouse
HRR: Oxygraph-2k
2023-08, Labelling
