ArticleCell reports2016
Hepatocyte DACH1 Is Increased in Obesity via Nuclear Exclusion of HDAC4 and Promotes Hepatic Insulin Resistance.
Article in Cell reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 34 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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Who cites it
34 citing papers in PubMed, 50 citations in OpenAlex.
- Hepatic PDIA5 improves hyperglycaemia and insulin resistance through stabilisation of ATF6.Diabetologia · 2026Article
- The histone deacetylase family in health and disease.Signal transduction and targeted therapy · 2026Review
- Two Sides of a Coin: Molecular, metabolic, and Phenotypic Convergence in Pediatric Undernutrition and Obesity.Current obesity reports · 2026Review
- Article
- RAP1A suppresses hepatic steatosis by regulating amino acid-mediated mTORC1 activation.JHEP reports : innovation in hepatology · 2025Article
- Roles of Histone Deacetylase 4 in the Inflammatory and Metabolic Processes.Diabetes & metabolism journal · 2024Review
- TheViruses · 2023Article
- Intracellular tPA-PAI-1 interaction determines VLDL assembly in hepatocytes.Science (New York, N.Y.) · 2023Article
- Retinal determination gene networks: from biological functions to therapeutic strategies.Biomarker research · 2023Review
- The PTP1B inhibitor MSI-1436 ameliorates liver insulin sensitivity by modulating autophagy, ER stress and systemic inflammation in Equine metabolic syndrome affected horses.Frontiers in endocrinology · 2023Article
- HDAC4 in cancer: A multitasking platform to drive not only epigenetic modifications.Frontiers in molecular biosciences · 2023Review
- Endoplasmic reticulum stress in innate immune cells - a significant contribution to non-alcoholic fatty liver disease.Frontiers in immunology · 2022Review
- A small molecule UPR modulator for diabetes identified by high throughput screening.Acta pharmaceutica Sinica. B · 2021Article
- Adipocyte CAMK2 deficiency improves obesity-associated glucose intolerance.Molecular metabolism · 2021Article
- Insects as a New Complex Model in Hormonal Basis of Obesity.International journal of molecular sciences · 2021Review
- Protein acetylation: a novel modus of obesity regulation.Journal of molecular medicine (Berlin, Germany) · 2021Review
- Endoplasmic Reticulum Stress and Autophagy in the Pathogenesis of Non-alcoholic Fatty Liver Disease (NAFLD): Current Evidence and Perspectives.Current obesity reports · 2021Review
- Regulation of Hepatic Metabolism and Cell Growth by the ATF/CREB Family of Transcription Factors.Diabetes · 2021Review
- ER Stress-Sensor Proteins and ER-Mitochondrial Crosstalk-Signaling Beyond (ER) Stress Response.Biomolecules · 2021Review
- Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Defective insulin signaling in hepatocytes is a key factor in type 2 diabetes. In obesity, activation of calcium/calmodulin-dependent protein kinase II (CaMKII) in hepatocytes suppresses ATF6, which triggers a PERK-ATF4-TRB3 pathway that disrupts insulin signaling. Elucidating how CaMKII suppresses ATF6 is therefore essential to understanding this insulin resistance pathway. We show that CaMKII phosphorylates and blocks nuclear translocation of histone deacetylase 4 (HDAC4). As a result, HDAC4-mediated SUMOylation of the corepressor DACH1 is decreased, which protects DACH1 from proteasomal degradation. DACH1, together with nuclear receptor corepressor (NCOR), represses Atf6 transcription, leading to activation of the PERK-TRB3 pathway and defective insulin signaling. DACH1 is increased in the livers of obese mice and humans, and treatment of obese mice with liver-targeted constitutively nuclear HDAC4 or DACH1 small hairpin RNA (shRNA) increases ATF6, improves hepatocyte insulin signaling, and protects against hyperglycemia and hyperinsulinemia. Thus, DACH1-mediated corepression in hepatocytes emerges as an important link between obesity and insulin resistance.
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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.