ArticleThe Journal of clinical investigation2009
Sumoylated PPARalpha mediates sex-specific gene repression and protects the liver from estrogen-induced toxicity in mice.
Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
What it found
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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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
55 citing papers in PubMed, 124 citations in OpenAlex.
- PLX3397 Reshapes Hepatic Lipid Metabolism Independent of Microglial Depletion.Neuroscience bulletin · 2026Article
- PPARα: Linking Cardiac Metabolism to Therapeutic Opportunities in Cardiovascular Diseases.Cells · 2026Review
- Peroxisome Proliferator-Activated Receptors (PPARs): A Themed Issue in Honor of Prof. Walter Wahli.Biomolecules · 2025Article
- Liver specific transgenic expression of CYP7B1 attenuates early western diet-induced MASLD progression.Journal of lipid research · 2025Article
- Activation of Genes by Nuclear Receptor/Specificity Protein (Sp) Interactions in Cancer.Cancers · 2025Review
- Review
- PPAR-Targeted Therapies in the Treatment of Non-Alcoholic Fatty Liver Disease in Diabetic Patients.International journal of molecular sciences · 2022Review
- Mechanistic insights into the peroxisome proliferator-activated receptor alpha as a transcriptional suppressor.Frontiers in medicine · 2022Review
- PPARα: An emerging target of metabolic syndrome, neurodegenerative and cardiovascular diseases.Frontiers in endocrinology · 2022Review
- Peroxisome Proliferator-Activated Receptors (PPARs) and Oxidative Stress in Physiological Conditions and in Cancer.Antioxidants (Basel, Switzerland) · 2021Review
- The transcription factors CREBH, PPARa, and FOXO1 as critical hepatic mediators of diet-induced metabolic dysregulation.The Journal of nutritional biochemistry · 2021Review
- Oleuropein-Induced Acceleration of Cytochrome P450-Catalyzed Drug Metabolism: Central Role for Nuclear Receptor Peroxisome Proliferator-Activated Receptor α.Drug metabolism and disposition: the biological fate of chemicals · 2021Article
- Review
- The pregnane X receptor drives sexually dimorphic hepatic changes in lipid and xenobiotic metabolism in response to gut microbiota in mice.Microbiome · 2021Article
- High Expression Level of PPARγ in CD24 Knockout Mice and Gender-Specific Metabolic Changes: A Model of Insulin-Sensitive Obesity.Journal of personalized medicine · 2021Article
- Sex-, Age-, and Race/Ethnicity-Dependent Variations in Drug-Processing and NRF2-Regulated Genes in Human Livers.Drug metabolism and disposition: the biological fate of chemicals · 2021Article
- The impact of sex on gene expression across human tissues.Science (New York, N.Y.) · 2020Article
- Not So Slim Anymore-Evidence for the Role of SUMO in the Regulation of Lipid Metabolism.Biomolecules · 2020Review
- Review
- Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
As most metabolic studies are conducted in male animals, understanding the sex specificity of the underlying molecular pathways has been broadly neglected; for example, whether PPARs elicit sex-dependent responses has not been determined. Here we show that in mice, PPARalpha has broad female-dependent repressive actions on hepatic genes involved in steroid metabolism and immunity. In male mice, this effect was reproduced by the administration of a synthetic PPARalpha ligand. Using the steroid oxysterol 7alpha-hydroxylase cytochrome P4507b1 (Cyp7b1) gene as a model, we elucidated the molecular mechanism of this sex-specific PPARalpha-dependent repression. Initial sumoylation of the ligand-binding domain of PPARalpha triggered the interaction of PPARalpha with GA-binding protein alpha (GABPalpha) bound to the target Cyp7b1 promoter. Histone deacetylase and DNA and histone methylases were then recruited, and the adjacent Sp1-binding site and histones were methylated. These events resulted in loss of Sp1-stimulated expression and thus downregulation of Cyp7b1. Physiologically, this repression conferred on female mice protection against estrogen-induced intrahepatic cholestasis, the most common hepatic disease during pregnancy, suggesting a therapeutic target for prevention of this disease.
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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.