ArticleNature communications2020
Chronic activation of hexosamine biosynthesis in the heart triggers pathological cardiac remodeling.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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
67 citing papers in PubMed, 89 citations in OpenAlex.
- Tissue-specific expression and regulation of congenital disorders of glycosylation genes: A GTEx-based in silico study.Molecular genetics and metabolism reports · 2026Article
- Diet-Associated Regulation of Cardiac Metabolism: Molecular Determinants and Pathophysiological Consequences.Nutrients · 2026Review
- Sam68 Exacerbates Pathologic Cardiac Hypertrophy by Suppressing Cardiomyocyte Glucose Oxidation.Circulation · 2026Article
- SGLT2 Inhibitors in Hypertrophic Cardiomyopathy: Emerging Evidence and Putative Mechanisms.Biomolecules · 2026Review
- O-GlcNAcylation: A bridge for regulating the function of the "heart-kidney-bone axis".Biochemistry and biophysics reports · 2026Review
- O-GlcNAcylation as a Metabolic Integrator in Cardiovascular Physiology and Disease.International journal of molecular sciences · 2026Review
- Glucosamine links hyperglycemia to mTORC1 activation and glucose toxicity in diabetes.JCI insight · 2026Article
- Hyaluronan in cardiac disease: implications for the extracellular matrix beyond collagen.American journal of physiology. Heart and circulatory physiology · 2026Review
- Phosphoproteomics identification of ERK-dependent activation of Rps6kb1 in cardiac hypertrophy.JCI insight · 2026Article
- Regulatory mechanism of O-linked N-acetylglucosamine protein modification on autophagy in cancer.Clinical and translational medicine · 2026Review
- O-GlcNAcylation in diabetic cardiac remodeling and a proposed endothelial-macrophage-fibroblast network.Frontiers in immunology · 2026Review
- Glutamine: fructose-6-phosphate amidotransferase (GFAT) in the pathology of diseases: a review.Cell death discovery · 2025Review
- Chronic hyperglycemia and cardiovascular dysfunction: an in-depth exploration of metabolic and cellular pathways in type 2 diabetes mellitus.Cardiovascular diabetology. Endocrinology reports · 2025Review
- Excessive glycosylation drives thoracic aortic aneurysm formation through integrated stress response.European heart journal · 2025Article
- Protein O-GlcNAcylation in Health and Diseases.MedComm · 2025Review
- Adropin protects against cardiac remodeling and metabolic dysfunction in a mouse model of HFpEF.bioRxiv : the preprint server for biology · 2025Article
- Empagliflozin enhances metabolic efficiency and improves left ventricular hypertrophy in a hypertrophic cardiomyopathy mouse model.European heart journal · 2025Article
- Exploring the metabolic signaling network of GFPT in cancer.Cell death discovery · 2025Review
- O-GlcNAcylation promotes angiogenic transdifferentiation to reverse vascular ischemia.Nature cardiovascular research · 2025Article
- An NRF2/β3-Adrenoreceptor Axis Drives a Sustained Antioxidant and Metabolic Rewiring Through the Pentose-Phosphate Pathway to Alleviate Cardiac Stress.Circulation · 2025Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
The hexosamine biosynthetic pathway (HBP) plays critical roles in nutrient sensing, stress response, and cell growth. However, its contribution to cardiac hypertrophic growth and heart failure remains incompletely understood. Here, we show that the HBP is induced in cardiomyocytes during hypertrophic growth. Overexpression of Gfat1 (glutamine:fructose-6-phosphate amidotransferase 1), the rate-limiting enzyme of HBP, promotes cardiomyocyte growth. On the other hand, Gfat1 inhibition significantly blunts phenylephrine-induced hypertrophic growth in cultured cardiomyocytes. Moreover, cardiac-specific overexpression of Gfat1 exacerbates pressure overload-induced cardiac hypertrophy, fibrosis, and cardiac dysfunction. Conversely, deletion of Gfat1 in cardiomyocytes attenuates pathological cardiac remodeling in response to pressure overload. Mechanistically, persistent upregulation of the HBP triggers decompensated hypertrophy through activation of mTOR while Gfat1 deficiency shows cardioprotection and a concomitant decrease in mTOR activity. Taken together, our results reveal that chronic upregulation of the HBP under hemodynamic stress induces pathological cardiac hypertrophy and heart failure through persistent activation of mTOR.
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.