ArticlePLoS genetics2014
Retinoic acid-related orphan receptor γ (RORγ): a novel participant in the diurnal regulation of hepatic gluconeogenesis and insulin sensitivity.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
60 citing papers in PubMed, 93 citations in OpenAlex.
- Associations between multiple metabolic indices and circadian syndrome: a cross-sectional study with mediation analysis of the C-reactive protein triglyceride glucose index.Hormones (Athens, Greece) · 2026Article
- Exome-wide association study of blood lipids in 1,158,017 individuals from diverse populations.Nature genetics · 2026Article
- Regulation of PKM2 expression and function by GLIS3 during metabolic reprogramming in polycystic kidneys.Experimental & molecular medicine · 2026Article
- RORγ drives non-small cell lung cancer progression by upregulating the NGF signaling.Respiratory research · 2026Article
- Identification and Validation of RORC as a Circadian Rhythm-Related Biomarker in Gastric Cancer.International journal of general medicine · 2026Article
- Review
- Identification of New Lupane-Type Triterpenoids as Inverse Agonists of RAR-Related Orphan Receptor Gamma (RORγ).Journal of natural products · 2025Article
- Identification of a Novel Indolizine RORγT Inverse Agonist Using the AI-Driven Drug Design Platform.ACS medicinal chemistry letters · 2025Article
- Role of acitretin in regulating glucose and lipid homeostasis in an imiquimod-induced psoriasis model mouse.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Article
- RORα fine-tunes the circadian control of hepatic triglyceride synthesis and gluconeogenesis.Scientific reports · 2025Article
- Knockouts ofiScience · 2024Article
- International Union of Basic and Clinical Pharmacology CXIII: Nuclear Receptor Superfamily-Update 2023.Pharmacological reviews · 2023Review
- Chronic Glucocorticoid Exposure Induced an S1PR2-RORγ Axis to Enhance Hepatic Gluconeogenesis in Male Mice.Diabetes · 2023Article
- CD36 regulates diurnal glucose metabolism and hepatic clock to maintain glucose homeostasis in mice.iScience · 2023Article
- New uses for an old remedy: Digoxin as a potential treatment for steatohepatitis and other disorders.World journal of gastroenterology · 2023Review
- Circadian gene expression in mouse renal proximal tubule.American journal of physiology. Renal physiology · 2023Article
- Identification of the Natural Steroid Sapogenin Diosgenin as a Direct Dual-Specific RORα/γ Inverse Agonist.Biomedicines · 2022Article
- Article
- Article
- Circadian rhythms in metabolic organs and the microbiota during acute fasting in mice.Physiological reports · 2022Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The hepatic circadian clock plays a key role in the daily regulation of glucose metabolism, but the precise molecular mechanisms that coordinate these two biological processes are not fully understood. In this study, we identify a novel connection between the regulation of RORγ by the clock machinery and the diurnal regulation of glucose metabolic networks. We demonstrate that particularly at daytime, mice deficient in RORγ exhibit improved insulin sensitivity and glucose tolerance due to reduced hepatic gluconeogenesis. This is associated with a reduced peak expression of several glucose metabolic genes critical in the control of gluconeogenesis and glycolysis. Genome-wide cistromic profiling, promoter and mutation analysis support the concept that RORγ regulates the transcription of several glucose metabolic genes directly by binding ROREs in their promoter regulatory region. Similar observations were made in liver-specific RORγ-deficient mice suggesting that the changes in glucose homeostasis were directly related to the loss of hepatic RORγ expression. Altogether, our study shows that RORγ regulates several glucose metabolic genes downstream of the hepatic clock and identifies a novel metabolic function for RORγ in the diurnal regulation of hepatic gluconeogenesis and insulin sensitivity. The inhibition of the activation of several metabolic gene promoters by an RORγ antagonist suggests that antagonists may provide a novel strategy in the management of metabolic diseases, including type 2 diabetes.
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Registered trials
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.