ArticleJCI insight2017
Nox4 reprograms cardiac substrate metabolism via protein O-GlcNAcylation to enhance stress adaptation.
Article in JCI insight, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 57 citations in OpenAlex.
- Review
- Nicotinamide adenine dinucleotide phosphate oxidase 4 in lung disease: a review of its biology and therapeutic potential.Experimental biology and medicine (Maywood, N.J.) · 2026Review
- Unraveling the interplay between RAS axes and NOX signaling in fibroblasts during cardiac fibrosis.Molecular and cellular biochemistry · 2026Review
- Updated insights on ASK1 signaling: mechanisms, regulation, and therapeutic potential in diseases.Molecular and cellular biochemistry · 2025Review
- The Dual Role of NOX4 in Cardiovascular Diseases: Driver of Oxidative Stress and Mediator of Adaptive Remodeling.Antioxidants (Basel, Switzerland) · 2025Review
- Sex-specific metabolic responses to high-fat diet in mice with NOX4 deficiency.Redox biology · 2025Article
- The role of protein O-GlcNAcylation in diabetic cardiomyopathy.Biochemical Society transactions · 2024Review
- Roles of O-GlcNAcylation in Mitochondrial Homeostasis and Cardiovascular Diseases.Antioxidants (Basel, Switzerland) · 2024Review
- Interplay between energy metabolism and NADPH oxidase-mediated pathophysiology in cardiovascular diseases.Frontiers in pharmacology · 2024Review
- Health position paper and redox perspectives on reactive oxygen species as signals and targets of cardioprotection.Redox biology · 2023Review
- Sustained Increases in Cardiomyocyte ProteinJournal of the American Heart Association · 2023Article
- Comparative multi-omic analyses of cardiac mitochondrial stress in three mouse models of frataxin deficiency.Disease models & mechanisms · 2023Article
- Review
- The regulation of cardiac intermediary metabolism by NADPH oxidases.Cardiovascular research · 2023Review
- Review
- Mutant CHCHD10 causes an extensive metabolic rewiring that precedes OXPHOS dysfunction in a murine model of mitochondrial cardiomyopathy.Cell reports · 2022Article
- New Insights Into Energy Substrate Utilization and Metabolic Remodeling in Cardiac Physiological Adaption.Frontiers in physiology · 2022Review
- A nexus of lipid andFrontiers in endocrinology · 2022Review
- The dual role of the hexosamine biosynthetic pathway in cardiac physiology and pathophysiology.Frontiers in endocrinology · 2022Review
- Cardiomyocyte protein O-GlcNAcylation is regulated by GFAT1 not GFAT2.Biochemical and biophysical research communications · 2021Article
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 4 countries.
Funding
Abstract
Cardiac hypertrophic remodeling during chronic hemodynamic stress is associated with a switch in preferred energy substrate from fatty acids to glucose, usually considered to be energetically favorable. The mechanistic interrelationship between altered energy metabolism, remodeling, and function remains unclear. The ROS-generating NADPH oxidase-4 (Nox4) is upregulated in the overloaded heart, where it ameliorates adverse remodeling. Here, we show that Nox4 redirects glucose metabolism away from oxidation but increases fatty acid oxidation, thereby maintaining cardiac energetics during acute or chronic stresses. The changes in glucose and fatty acid metabolism are interlinked via a Nox4-ATF4-dependent increase in the hexosamine biosynthetic pathway, which mediates the attachment of O-linked N-acetylglucosamine (O-GlcNAcylation) to the fatty acid transporter CD36 and enhances fatty acid utilization. These data uncover a potentially novel redox pathway that regulates protein O-GlcNAcylation and reprograms cardiac substrate metabolism to favorably modify adaptation to chronic stress. Our results also suggest that increased fatty acid oxidation in the chronically stressed heart may be beneficial.
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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.