ArticleThe Journal of biological chemistry2012
Orphan nuclear receptor estrogen-related receptor γ (ERRγ) is key regulator of hepatic gluconeogenesis.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 134 citations in OpenAlex.
- Molecular regulation of PGC-1α: from protein-protein interactions and post-translational modifications to pharmacological modulation.Journal of molecular medicine (Berlin, Germany) · 2026Review
- Cereblon enhances hepatic hepcidin production through estrogen-related receptor gamma activation.BMB reports · 2026Article
- Protein O-GlcNAcylation in Health and Diseases.MedComm · 2025Review
- Article
- Gradual DNA methylation changes reveal transcription factors implicated in metabolic dysfunction-associated steatotic liver disease progression and epigenetic age acceleration.Clinical epigenetics · 2025Article
- Estrogen-related receptor gamma is a regulator of mitochondrial, autophagy, and immediate-early gene programs in spiny projection neurons: Relevance for transcriptional changes in Huntington disease.Neurobiology of disease · 2025Article
- The Estrogen Receptor-Related Orphan Receptors Regulate Autophagy through TFEB.Molecular pharmacology · 2024Article
- Estrogen-related receptor alpha promotes thyroid tumor cell survival via a tumor subtype-specific regulation of target gene networks.Oncogene · 2024Article
- A Synthetic ERR Agonist Alleviates Metabolic Syndrome.The Journal of pharmacology and experimental therapeutics · 2024Article
- Activation of estrogen-related receptor γ by calcium and cadmium.Frontiers in endocrinology · 2024Article
- A computational assay for identifying millet-derived compounds that antagonize the interaction between bisphenols and estrogen-related receptor gamma.Frontiers in pharmacology · 2024Article
- Research Progress in Estrogen-related Receptor Gamma (ERRγ) Agonists and Inverse Agonists.Current medicinal chemistry · 2024Review
- TCDD dysregulation of lncRNA expression, liver zonation and intercellular communication across the liver lobule.Toxicology and applied pharmacology · 2023Article
- Article
- TCDD dysregulation of lncRNA expression, liver zonation and intercellular communication across the liver lobule.bioRxiv : the preprint server for biology · 2023Article
- An Inverse Agonist GSK5182 Increases Protein Stability of the Orphan Nuclear Receptor ERRγ via Inhibition of Ubiquitination.International journal of molecular sciences · 2022Article
- Milk Exosomal microRNAs: Postnatal Promoters of β Cell Proliferation but Potential Inducers of β Cell De-Differentiation in Adult Life.International journal of molecular sciences · 2022Review
- Oxidative Stress, Genomic Integrity, and Liver Diseases.Molecules (Basel, Switzerland) · 2022Review
- Are BPA Substitutes as Obesogenic as BPA?International journal of molecular sciences · 2022Review
- Melatonin Regulates Iron Homeostasis by Inducing Hepcidin Expression in Hepatocytes.International journal of molecular sciences · 2022Article
13 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glucose homeostasis is tightly controlled by hormonal regulation of hepatic glucose production. Dysregulation of this system is often associated with insulin resistance and diabetes, resulting in hyperglycemia in mammals. Here, we show that the orphan nuclear receptor estrogen-related receptor γ (ERRγ) is a novel downstream mediator of glucagon action in hepatic gluconeogenesis and demonstrate a beneficial impact of the inverse agonist GSK5182. Hepatic ERRγ expression was increased by fasting-dependent activation of the cAMP-response element-binding protein-CRTC2 pathway. Overexpression of ERRγ induced Pck1 and G6PC gene expression and glucose production in primary hepatocytes, whereas abolition of ERRγ gene expression attenuated forskolin-mediated induction of gluconeogenic gene expression. Deletion and mutation analyses of the Pck1 promoter showed that ERRγ directly regulates the Pck1 gene transcription via ERR response elements of the Pck1 promoter as confirmed by ChIP assay and in vivo imaging analysis. We also demonstrate that GSK5182, an inverse agonist of ERRγ, specifically inhibits the transcriptional activity of ERRγ in a PGC-1α dependent manner. Finally, the ERRγ inverse agonist ameliorated hyperglycemia through inhibition of hepatic gluconeogenesis in db/db mice. Control of hepatic glucose production by an ERRγ-specific inverse agonist is a new potential therapeutic approach for the treatment of type 2 diabetes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.