ArticleMolecular endocrinology (Baltimore, Md.)2009
Down-regulation of hepatic HNF4alpha gene expression during hyperinsulinemia via SREBPs.
Article in Molecular endocrinology (Baltimore, Md.), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 116 citations in OpenAlex.
- The Green Path to Liver Health: Herbal Solutions for Non-alcoholic Steatohepatitis.Cardiovascular & hematological disorders drug targets · 2025Pooled it
- The effects of ezetimibe on non-alcoholic fatty liver disease and glucose metabolism: a randomised controlled trial.Diabetologia · 2014Trial
- Sex hormone-binding globulin and coronary heart disease: a narrative review of associations and biomarker potential.Journal of thoracic disease · 2026Review
- N-(2-Hydroxyphenyl)-2-propylpentanamide Modulates HDAC1 and GPER1 Expression in a Rodent Model of Triple-Negative Breast Cancer.Biomedicines · 2026Article
- Downregulation of hepatic sulfotransferase 1E1 expression associated with decreased expression of multidrug resistance-associated protein 2.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Sex Hormone-Binding Globulin and Metabolic Syndrome in Children and Adolescents: A Focus on Puberty.Metabolites · 2025Review
- Mammalian Ste20-like kinase 1 regulates AMPK to mitigate the progression of non-alcoholic fatty liver disease.European journal of medical research · 2025Article
- Inhibition of microRNA-33b in humanized mice ameliorates nonalcoholic steatohepatitis.Life science alliance · 2023Article
- The transcription factor HNF-4α: a key player in haematological disorders.Archives of medical science : AMS · 2023Article
- HNF4α isoforms: the fraternal twin master regulators of liver function.Frontiers in endocrinology · 2023Review
- The Accelerated Progression of Atherosclerosis Correlates with Decreased miR-33a and miR-21 and Increased miR-122 and miR-3064-5p in Circulation and the Liver of ApoE-/- Mice with Streptozocin (STZ)-Induced Type 2 Diabetes.Current issues in molecular biology · 2022Article
- Hepatic circadian and differentiation factors control liver susceptibility for fatty liver disease and tumorigenesis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- High levels of FSH before puberty are associated with increased risk of metabolic syndrome during pubertal transition.Pediatric obesity · 2022Article
- Crosstalk of hepatocyte nuclear factor 4a and glucocorticoid receptor in the regulation of lipid metabolism in mice fed a high-fat-high-sugar diet.Lipids in health and disease · 2022Article
- Effect of Sex Hormone-Binding Globulin on Polycystic Ovary Syndrome: Mechanisms, Manifestations, Genetics, and Treatment.International journal of women's health · 2022Review
- Role of Cholesterol-Associated Steatohepatitis in the Development of NASH.Hepatology communications · 2022Review
- Hepatocyte-Specific Hepatocyte Nuclear Factor 4 Alpha (HNF4) Deletion Decreases Resting Energy Expenditure by Disrupting Lipid and Carbohydrate Homeostasis.Gene expression · 2021Article
- Research on the circadian clock gene HNF4a in different malignant tumors.International journal of medical sciences · 2021Article
- Sex Hormone-Binding Globulin (SHBG) as an Early Biomarker and Therapeutic Target in Polycystic Ovary Syndrome.International journal of molecular sciences · 2020Review
- The hepatic lipidome and HNF4α and SHBG expression in human liver.Endocrine connections · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Mutations in the coding region of hepatocyte nuclear factor 4alpha (HNF4alpha), and its upstream promoter (P2) that drives expression in the pancreas, are known to lead to maturity-onset diabetes of the young 1 (MODY1). HNF4alpha also controls gluconeogenesis and lipid metabolism in the liver, where the proximal promoter (P1) predominates. However, very little is known about the role of hepatic HNF4alpha in diabetes. Here, we examine the expression of hepatic HNF4alpha in two diabetic mouse models, db/db mice (type 2, insulin resistant) and streptozotocin-treated mice (type 1, insulin deficient). We found that the level of HNF4alpha protein and mRNA was decreased in the liver of db/db mice but increased in streptozotocin-treated mice. Because insulin increases the activity of sterol regulatory element-binding proteins (SREBP)-1c and -2, we also examined the effect of SREBPs on hepatic HNF4alpha gene expression and found that, like insulin, ectopic expression of SREBPs decreases the level of hepatic HNF4alpha protein and mRNA both in vitro in primary hepatocytes and in vivo in the liver of C57BL/6 mice. Finally, we use gel shift, chromatin immunoprecipitation, small interfering RNA, and reporter gene analysis to show that SREBP2 binds the human HNF4alpha P1 promoter and negatively regulates its expression. These data indicate that hyperinsulinemia down-regulates HNF4alpha in the liver through the up-regulation of SREBPs, thereby establishing a link between these two critical transcription factor pathways that regulate lipid and glucose metabolism in the liver. These findings also provide new insights into diabetes-associated complications such as fatty liver disease.
Indexed as
Identifiers
What OpenQuestion holds
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.