ArticleCirculation. Arrhythmia and electrophysiology2019
Dietary Saturated Fat Promotes Arrhythmia by Activating NOX2 (NADPH Oxidase 2).
Article in Circulation. Arrhythmia and electrophysiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Red meat consumption and risk for dyslipidaemia and inflammation: A systematic review and meta-analysis.Frontiers in cardiovascular medicine · 2022Pooled it
- Role of NADPH oxidase 2-derived reactive oxygen species in cardiac electrophysiological disorders.Channels (Austin, Tex.) · 2026Review
- Metabolic Dysregulation in Laminopathies: Implications for Heart Failure and Cardiac Health.Current heart failure reports · 2026Review
- GPX3 improves endometrial receptivity by inhibiting ferroptosis via the Nrf2/GPX4 signaling pathway in sows.Zoological research · 2026Article
- Immune cells and arrhythmias.Cardiovascular research · 2025Review
- Modulation of NOX2 causes obesity-mediated atrial fibrillation.The Journal of clinical investigation · 2024Article
- Eicosapentaenoic Acid Rescues Cav1.2-L-Type CaInternational journal of molecular sciences · 2024Article
- Critical Role of Mitochondrial Fatty Acid Metabolism in Normal Cell Function and Pathological Conditions.International journal of molecular sciences · 2024Review
- Impact of Obesity on Atrial Fibrillation Pathogenesis and Treatment Options.Journal of the American Heart Association · 2024Review
- Obesity-induced activation of NADPH oxidase 2 prolongs cardiac repolarization via inhibiting K+ currents.PloS one · 2024Article
- Localized cardiomyocyte lipid accumulation is associated with slowed epicardial conduction in rats.The Journal of general physiology · 2023Article
- Endothelial cell-specific roles for tetrahydrobiopterin in myocardial function, cardiac hypertrophy, and response to myocardial ischemia-reperfusion injury.American journal of physiology. Heart and circulatory physiology · 2023Article
- Regular Exercise inInternational journal of molecular sciences · 2023Article
- Combined metabolomic and transcriptomic profiling approaches reveal the cardiac response to high-fat diet.iScience · 2022Article
- Overexpression of NOX2 Exacerbates AngII-Mediated Cardiac Dysfunction and Metabolic Remodelling.Antioxidants (Basel, Switzerland) · 2022Article
- The mitochondrial calcium uniporter promotes arrhythmias caused by high-fat diet.Scientific reports · 2021Article
- Phospho-ablation of cardiac sodium channel NaInternational journal of obesity (2005) · 2021Article
- Metformin Is Associated With a Lower Risk of Atrial Fibrillation and Ventricular Arrhythmias Compared With Sulfonylureas: An Observational Study.Circulation. Arrhythmia and electrophysiology · 2021Observational
- Identification and Verification of Feature Immune-Related Genes in Patients With Hypertrophic Cardiomyopathy Based on Bioinformatics Analyses.Frontiers in cardiovascular medicine · 2021Article
- Mechanisms of Chronic Metabolic Stress in Arrhythmias.Antioxidants (Basel, Switzerland) · 2020Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 3 countries.
Funding
Abstract
backgroundObesity and diets high in saturated fat increase the risk of arrhythmias and sudden cardiac death. However, the molecular mechanisms are not well understood. We hypothesized that an increase in dietary saturated fat could lead to abnormalities of calcium homeostasis and heart rhythm by a NOX2 (NADPH oxidase 2)-dependent mechanism.
methodsWe investigated this hypothesis by feeding mice high-fat diets. In vivo heart rhythm telemetry, optical mapping, and isolated cardiac myocyte imaging were used to quantify arrhythmias, repolarization, calcium transients, and intracellular calcium sparks.
resultsWe found that saturated fat activates NOX (NADPH oxidase), whereas polyunsaturated fat does not. The high saturated fat diet increased repolarization heterogeneity and ventricular tachycardia inducibility in perfused hearts. Pharmacological inhibition or genetic deletion of NOX2 prevented arrhythmogenic abnormalities in vivo during high statured fat diet and resulted in less inducible ventricular tachycardia. High saturated fat diet activates CaMK (Ca
conclusionsWe conclude that NOX2 deletion or pharmacological inhibition prevents the arrhythmogenic effects of a high saturated fat diet, in part mediated by activation of CaMK. This work reveals a molecular mechanism linking cardiac metabolism to arrhythmia and suggests that NOX2 inhibitors could be a novel therapy for heart rhythm abnormalities caused by cardiac lipid overload.
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Registered trials
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