ArticleMolecular metabolism2015
Molecular regulation of urea cycle function by the liver glucocorticoid receptor.
Article in Molecular metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers, 2 of them syntheses that pooled it.
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Who cites it
21 citing papers in PubMed, 2 syntheses or guidelines pooled it, 54 citations in OpenAlex.
- High-protein diets and testosterone.Nutrition and health · 2023Pooled it
- Low-carbohydrate diets and men's cortisol and testosterone: Systematic review and meta-analysis.Nutrition and health · 2022Pooled it
- Urea cycle dysregulation and arginine pathways in the pathogenesis of NAFLD and NASH (Review).International journal of molecular medicine · 2026Review
- Hepatic CBP/p300 Orchestrate Amino Acid-Driven Gluconeogenesis through Histone Crotonylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Emergence of dysfunctional neutrophils with a defect in arginase-1 release in severe COVID-19.JCI insight · 2024Article
- Generation and characterization of mature hepatocyte organoids for liver metabolic studies.Journal of cell science · 2024Article
- The Metabolic Syndrome, a Human Disease.International journal of molecular sciences · 2024Review
- Development of novel liver-targeting glucocorticoid prodrugs.Medicine in drug discovery · 2024Article
- Arginase 1 and L-arginine coordinate fetal lung development and the initiation of labor in mice.EMBO reports · 2023Article
- Narrative Review: Glucocorticoids in Alcoholic Hepatitis-Benefits, Side Effects, and Mechanisms.Journal of xenobiotics · 2022Review
- Lactational delivery of Triclosan promotes non-alcoholic fatty liver disease in newborn mice.Nature communications · 2022Article
- Dexamethasone modulates immature neutrophils and interferon programming in severe COVID-19.Nature medicine · 2022Article
- Noncoding sequence variants define a novel regulatory element in the first intron of the N-acetylglutamate synthase gene.Human mutation · 2021Article
- Best Practices and Progress in Precision-Cut Liver Slice Cultures.International journal of molecular sciences · 2021Review
- Liver alanine catabolism promotes skeletal muscle atrophy and hyperglycaemia in type 2 diabetes.Nature metabolism · 2021Article
- The Paired Siglecs in Brain Tumours Therapy: The Immunomodulatory Effect of Dexamethasone and Temozolomide in Human Glioma In Vitro Model.International journal of molecular sciences · 2021Article
- Dietary Energy Partition: The Central Role of Glucose.International journal of molecular sciences · 2020Review
- SWI/SNF complex subunit BAF60a represses hepatic ureagenesis through a crosstalk between YB-1 and PGC-1α.Molecular metabolism · 2020Article
- Multifaceted Control of GR Signaling and Its Impact on Hepatic Transcriptional Networks and Metabolism.Frontiers in endocrinology · 2020Review
- Mechanistic inferences on metabolic dysfunction in posttraumatic stress disorder from an integrated model and multiomic analysis: role of glucocorticoid receptor sensitivity.American journal of physiology. Endocrinology and metabolism · 2019Article
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveOne of the major side effects of glucocorticoid (GC) treatment is lean tissue wasting, indicating a prominent role in systemic amino acid metabolism. In order to uncover a novel aspect of GCs and their intracellular-receptor, the glucocorticoid receptor (GR), on metabolic control, we conducted amino acid and acylcarnitine profiling in human and mouse models of GC/GR gain- and loss-of-function.
methodsBlood serum and tissue metabolite levels were determined in Human Addison's disease (AD) patients as well as in mouse models of systemic and liver-specific GR loss-of-function (AAV-miR-GR) with or without dexamethasone (DEX) treatments. Body composition and neuromuscular and metabolic function tests were conducted in vivo and ex vivo, the latter using precision cut liver slices.
resultsA serum metabolite signature of impaired urea cycle function (i.e. higher [ARG]:[ORN + CIT]) was observed in human (CTRL: 0.45 ± 0.03, AD: 1.29 ± 0.04; p < 0.001) and mouse (AAV-miR-NC: 0.97 ± 0.13, AAV-miR-GR: 2.20 ± 0.19; p < 0.001) GC/GR loss-of-function, with similar patterns also observed in liver. Serum urea levels were consistently affected by GC/GR gain- (∼+32%) and loss (∼-30%) -of-function. Combined liver-specific GR loss-of-function with DEX treatment revealed a tissue-autonomous role for the GR to coordinate an upregulation of liver urea production rate in vivo and ex vivo, and prevent hyperammonaemia and associated neuromuscular dysfunction in vivo. Liver mRNA expression profiling and GR-cistrome mining identified Arginase I (ARG1) a urea cycle gene targeted by the liver GR.
conclusionsThe liver GR controls systemic and liver urea cycle function by transcriptional regulation of ARG1 expression.
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