ArticleThe Journal of clinical investigation2014
Cardiac-specific ablation of ARNT leads to lipotoxicity and cardiomyopathy.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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.
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.
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Who cites it
28 citing papers in PubMed, 41 citations in OpenAlex.
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- PPARα-NF-κB heterodimer mediates obesity-induced diastolic dysfunction through autocrine production of IL-6.The Journal of clinical investigation · 2026Article
- HIF-mediated hierarchical hypoxic adaptation, a novel paradigm in heart failure pathogenesis: is there a role for targeted therapies?Frontiers in pharmacology · 2026Review
- ARNT-dependent HIF-2α signaling protects cardiac microvascular barrier integrity and heart function post-myocardial infarction.Communications biology · 2025Article
- Cardiac lipid metabolism, mitochondrial function, and heart failure.Cardiovascular research · 2023Review
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- Hypoxia signaling in human health and diseases: implications and prospects for therapeutics.Signal transduction and targeted therapy · 2022Review
- HIF in the heart: development, metabolism, ischemia, and atherosclerosis.The Journal of clinical investigation · 2021Review
- Increase in Blood-Brain Barrier (BBB) Permeability Is Regulated by MMP3 via the ERK Signaling Pathway.Oxidative medicine and cellular longevity · 2021Article
- Hypoxia-Inducible Factors as Key Players in the Pathogenesis of Non-alcoholic Fatty Liver Disease and Non-alcoholic Steatohepatitis.Frontiers in medicine · 2021Review
- Endothelial Aryl Hydrocarbon Receptor Nuclear Translocator Mediates the Angiogenic Response to Peripheral Ischemia in Mice With Type 2 Diabetes Mellitus.Frontiers in cell and developmental biology · 2021Article
- Hypoxia-Inducible Factor Regulates Endothelial Metabolism in Cardiovascular Disease.Frontiers in physiology · 2021Review
- Gut dysbiosis induced by cardiac pressure overload enhances adverse cardiac remodeling in a T cell-dependent manner.Gut microbes · 2020Article
- Hypoxia-inducible factors and diabetes.The Journal of clinical investigation · 2020Review
- Diabetic atherosclerosis: is there a role for the hypoxia-inducible factors?Bioscience reports · 2020Review
- Inorganic nitrate, hypoxia, and the regulation of cardiac mitochondrial respiration-probing the role of PPARα.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Melatonin prevents Drp1-mediated mitochondrial fission in diabetic hearts through SIRT1-PGC1α pathway.Journal of pineal research · 2018Article
- Metabolic Suppression of HIF-1α Contributes to Susceptibility of Ischemic Injury in Diabetic Hearts.JACC. Basic to translational science · 2018Article
- PIMT/NCOA6IP Deletion in the Mouse Heart Causes Delayed Cardiomyopathy Attributable to Perturbation in Energy Metabolism.International journal of molecular sciences · 2018Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Patients with type 2 diabetes often present with cardiovascular complications; however, it is not clear how diabetes promotes cardiac dysfunction. In murine models, deletion of the gene encoding aryl hydrocarbon nuclear translocator (ARNT, also known as HIF1β) in the liver or pancreas leads to a diabetic phenotype; however, the role of ARNT in cardiac metabolism is unknown. Here, we determined that cardiac-specific deletion of Arnt in adult mice results in rapid development of cardiomyopathy (CM) that is characterized by accumulation of lipid droplets. Compared with hearts from ARNT-expressing mice, ex vivo analysis of ARNT-deficient hearts revealed a 2-fold increase in fatty acid (FA) oxidation as well as a substantial increase in the expression of PPARα and its target genes. Furthermore, deletion of both Arnt and Ppara preserved cardiac function, improved survival, and completely reversed the FA accumulation phenotype, indicating that PPARα mediates the detrimental effects of Arnt deletion in the heart. Finally, we determined that ARNT directly regulates Ppara expression by binding to its promoter and forming a complex with HIF2α. Together, these findings suggest that ARNT is a critical regulator of myocardial FA metabolism and that its deletion leads to CM and an increase in triglyceride accumulation through PPARα.
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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.