ArticleThe Journal of clinical investigation2018
Fasting-induced JMJD3 histone demethylase epigenetically activates mitochondrial fatty acid β-oxidation.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 82 citations in OpenAlex.
- Alternate-day fasting enhances leptin sensitivity via JMJD3-dependent epigenetic regulation of the leptin receptor in the hypothalamus.The Journal of nutritional biochemistry · 2026Article
- JMJD3-mediated HADH demethylation orchestrates hepatocyte maturation through fatty acid β-oxidation-dependent histone acetylation.Experimental & molecular medicine · 2026Article
- BAP1 and UTX are dispensable for transcription-driven Polycomb erasure but essential for enhancer establishment.The Journal of biological chemistry · 2026Article
- The role of hepatocyte epigenetics in the pathogenesis of metabolic dysfunction-associated steatotic liver disease.Communications medicine · 2026Review
- Sex-specific KDM6A-HNF4A-CREBH network controls lipoprotein cholesterol metabolism and atherosclerosis via epigenetic reprograming of hepatocytes.Nature communications · 2026Article
- The JMJD family histone demethylases: structure, mechanism of action, diseases and therapeutic targets.Molecular biomedicine · 2026Review
- Evaluating the potential causal relationship between carnitine-related metabolites and breast cancer: a Mendelian randomization and transcriptomic analysis.Archives of medical science : AMS · 2026Article
- Multiomics strategy-based obesity biomarkers discovery for precision medicine.International journal of obesity (2005) · 2026Review
- The Role of Hepatic SIRT1: From Metabolic Regulation to Immune Modulation and Multi-target Therapeutic Strategies.Journal of clinical and translational hepatology · 2025Review
- Oxidative-Inflammatory Crosstalk and Multi-Target Natural Agents: Decoding Diabetic Vascular Complications.Current issues in molecular biology · 2025Review
- Crosstalk between Epigenetics and Autophagy in Metabolic Dysfunction-Associated Steatotic Liver Disease.Journal of obesity & metabolic syndrome · 2025Review
- Dynamic Rendition of Adipose Genes Under Epigenetic Regulation: Revealing New Mechanisms of Obesity Occurrence.Current issues in molecular biology · 2025Review
- Bridging epigenomics and tumor immunometabolism: molecular mechanisms and therapeutic implications.Molecular cancer · 2025Review
- KDM6B-Mediated HADHA Demethylation/Lactylation Regulates Cementogenesis.Journal of dental research · 2025Article
- Homotherapy for heteropathy of chronic kidney disease and oligoasthenozoospermia through regulating SIRT1/NF-κB pathway by Shenqi pills.Frontiers in pharmacology · 2025Article
- White adipose tissue browning and peroxisome proliferator activated receptors in MASLD.Frontiers in endocrinology · 2025Review
- Low ACADM expression predicts poor prognosis and suppressive tumor microenvironment in clear cell renal cell carcinoma.Scientific reports · 2024Article
- Article
- Oxidative Stress: A Culprit in the Progression of Diabetic Kidney Disease.Antioxidants (Basel, Switzerland) · 2024Review
- Hammerhead-type FXR agonists induce an eRNAbioRxiv : the preprint server for biology · 2024Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
Jumonji D3 (JMJD3) histone demethylase epigenetically regulates development and differentiation, immunity, and tumorigenesis by demethylating a gene repression histone mark, H3K27-me3, but a role for JMJD3 in metabolic regulation has not been described. SIRT1 deacetylase maintains energy balance during fasting by directly activating both hepatic gluconeogenic and mitochondrial fatty acid β-oxidation genes, but the underlying epigenetic and gene-specific mechanisms remain unclear. In this study, JMJD3 was identified unexpectedly as a gene-specific transcriptional partner of SIRT1 and epigenetically activated mitochondrial β-oxidation, but not gluconeogenic, genes during fasting. Mechanistically, JMJD3, together with SIRT1 and the nuclear receptor PPARα, formed a positive autoregulatory loop upon fasting-activated PKA signaling and epigenetically activated β-oxidation-promoting genes, including Fgf21, Cpt1a, and Mcad. Liver-specific downregulation of JMJD3 resulted in intrinsic defects in β-oxidation, which contributed to hepatosteatosis as well as glucose and insulin intolerance. Remarkably, the lipid-lowering effects by JMJD3 or SIRT1 in diet-induced obese mice were mutually interdependent. JMJD3 histone demethylase may serve as an epigenetic drug target for obesity, hepatosteatosis, and type 2 diabetes that allows selective lowering of lipid levels without increasing glucose levels.
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