ArticleNature communications2017
RORα controls hepatic lipid homeostasis via negative regulation of PPARγ transcriptional network.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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Who cites it
93 citing papers in PubMed, 139 citations in OpenAlex.
- Time matters: circadian genetics and the molecular logic of human health and disease.Nature reviews. Genetics · 2026Review
- Myeloid deficiency of RORα exacerbates lipid dysregulation and laser-induced choroidal neovascularization.Angiogenesis · 2026Article
- The histone deacetylase family in health and disease.Signal transduction and targeted therapy · 2026Review
- Discovery of circadian clock activators with anti-obesity efficacy via suppression of adipocyte development and hypertrophy.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Restoration of oxidative stress by HNF4α deletion in VWA8-null hepatocytes.Biochemistry and biophysics reports · 2026Article
- SMRT regulation of nuclear receptors orchestrates bile acid homeostasis.Experimental & molecular medicine · 2026Article
- Hepatocyte-Specific RORα Deficiency Accelerates Liver Regeneration by Unleashing ME1-Driven Glycolysis.Genes · 2026Article
- Circadian rhythm of melatonin receptors under monochromatic light and their regulatory effect on clock genes in the chick liver.Poultry science · 2026Article
- Quercetin and Fisetin activate circadian clock via RORα and inhibit adipocyte growth.bioRxiv : the preprint server for biology · 2026Article
- Clock Modulation by Naringenin Suppresses Lipogenesis and Promotes Adipose Tissue Browning.Journal of cellular physiology · 2026Article
- Developmental programming: gestational exposure to excess testosterone disrupts maternal steroid homeostasis and perturbs the steroid-lipid relationship in sheep.Molecular and cellular endocrinology · 2026Article
- The metabolic dysfunction-associated steatohepatitis (MASH) drug resmetirom exhibits broad nuclear receptor activity with minimal functional impact.Scientific reports · 2026Article
- RORα: a critical nexus in the crosstalk between cholesterol metabolism and macrophage polarization.Frontiers in immunology · 2026Review
- Exercise Impacts Liver Disease: Balancing Metabolic and Immune Homeostasis.International journal of biological sciences · 2026Review
- Genome-wide interaction study with body mass index identifies CYP7A1 and GIPR as genetic modulators of metabolic dysfunction-associated steatotic liver disease.Clinical and molecular hepatology · 2025Article
- The Framingham steatosis index as a predictor of advanced CKM syndrome in US adults: Evidence from NHANES 2001 to 2018.Medicine · 2025Article
- Clock Modulation by Naringenin via RORα Suppresses Lipogenesis and Promotes Adipose Tissue Browning.bioRxiv : the preprint server for biology · 2025Article
- Targeting Liver Epsins Ameliorates Dyslipidemia in Atherosclerosis through Inhibition of Proprotein Convertase Subtilisin/Kexin Type 9-Mediated Low-density Lipoprotein Receptor Degradation.bioRxiv : the preprint server for biology · 2025Article
- Genetic Loss of RORα Impairs Visual Function With Rod Bipolar Cell Degeneration In Mice.Investigative ophthalmology & visual science · 2025Article
- Direct regulation of Per2 by Roraa: insights into circadian and metabolic interplay in zebrafish.Cellular and molecular life sciences : CMLS · 2025Article
33 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The retinoic acid receptor-related orphan receptor-α (RORα) is an important regulator of various biological processes, including cerebellum development, circadian rhythm and cancer. Here, we show that hepatic RORα controls lipid homeostasis by negatively regulating transcriptional activity of peroxisome proliferators-activated receptor-γ (PPARγ) that mediates hepatic lipid metabolism. Liver-specific Rorα-deficient mice develop hepatic steatosis, obesity and insulin resistance when challenged with a high-fat diet (HFD). Global transcriptome analysis reveals that liver-specific deletion of Rorα leads to the dysregulation of PPARγ signaling and increases hepatic glucose and lipid metabolism. RORα specifically binds and recruits histone deacetylase 3 (HDAC3) to PPARγ target promoters for the transcriptional repression of PPARγ. PPARγ antagonism restores metabolic homeostasis in HFD-fed liver-specific Rorα deficient mice. Our data indicate that RORα has a pivotal role in the regulation of hepatic lipid homeostasis. Therapeutic strategies designed to modulate RORα activity may be beneficial for the treatment of metabolic disorders.Hepatic steatosis development may result from dysregulation of lipid metabolism, which is finely tuned by several transcription factors including the PPAR family. Here Kim et al. show that the nuclear receptor RORα inhibits PPARγ-mediated transcriptional activity by interacting with HDAC3 and competing for the promoters of lipogenic genes.
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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.