ArticleThe Journal of biological chemistry2018
Coenzyme A-mediated degradation of pyruvate dehydrogenase kinase 4 promotes cardiac metabolic flexibility after high-fat feeding in mice.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 23 citations in OpenAlex.
- Article
- Myocardial oxygen consumption, myocardial efficiency, and mechanical efficiency: A review across pathologic and physiologic states.Physiological reports · 2026Review
- In vivo assessment of the recovery of myocardial pyruvate dehydrogenase activity following a ketogenic diet.Cardiovascular research · 2026Article
- Integration of ATAC-Seq, Transcriptomic, and Proteomics Reveals the Molecular Mechanism of Intramuscular Fat Deposition and Meat Tenderness Regulation in Pig Breeds.Biomolecules · 2025Article
- Myocardial pyruvate dehydrogenase kinase 4 drives sex-specific cardiac responses to endotoxemia.JCI insight · 2025Article
- Mitochondria at the Heart of Sepsis: Mechanisms, Metabolism, and Sex Differences.International journal of molecular sciences · 2025Review
- Molecular Targets and Small Molecules Modulating Acetyl Coenzyme A in Physiology and Diseases.ACS pharmacology & translational science · 2025Review
- Inhibition of Pyruvate Dehydrogenase in the Heart as an Initiating Event in the Development of Diabetic Cardiomyopathy.Antioxidants (Basel, Switzerland) · 2023Review
- Inhibition of pyruvate dehydrogenase kinase improves carbohydrate utilization in Nile tilapia by regulating PDK2/4-PDHE1α axis and insulin sensitivity.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2022Article
- A structure and function relationship study to identify the impact of the R721G mutation in the human mitochondrial lon protease.Archives of biochemistry and biophysics · 2021Article
- PKM1 Exerts Critical Roles in Cardiac Remodeling Under Pressure Overload in the Heart.Circulation · 2021Article
- Xbp1s-FoxO1 axis governs lipid accumulation and contractile performance in heart failure with preserved ejection fraction.Nature communications · 2021Article
- ROS-dependent HIF1α activation under forced lipid catabolism entails glycolysis and mitophagy as mediators of higher proliferation rate in cervical cancer cells.Journal of experimental & clinical cancer research : CR · 2021Article
- FOXO1 contributes to diabetic cardiomyopathy via inducing imbalanced oxidative metabolism in type 1 diabetes.Journal of cellular and molecular medicine · 2020Article
- Maternal low protein diet induces persistent expression changes in metabolic genes in male rats.World journal of diabetes · 2020Article
- Enhancing cardiac glycolysis causes an increase in PDK4 content in response to short-term high-fat diet.The Journal of biological chemistry · 2019Article
- Microenvironmental control of glucose metabolism in tumors by regulation of pyruvate dehydrogenase.International journal of cancer · 2019Review
- Propionate-induced changes in cardiac metabolism, notably CoA trapping, are not altered by l-carnitine.American journal of physiology. Endocrinology and metabolism · 2018Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Cardiac energy is produced primarily by oxidation of fatty acids and glucose, with the relative contributions of each nutrient being sensitive to changes in substrate availability and energetic demand. A major contributor to cardiac metabolic flexibility is pyruvate dehydrogenase (PDH), which converts glucose-derived pyruvate to acetyl-CoA within the mitochondria. PDH is inhibited by phosphorylation dependent on the competing activities of pyruvate dehydrogenase kinases (PDK1-4) and phosphatases (PDP1-2). A single high-fat meal increases cardiac PDK4 content and subsequently inhibits PDH activity, reducing pyruvate utilization when abundant fatty acids are available. In this study, we demonstrate that diet-induced increases in PDK4 are reversible and characterize a novel pathway that regulates PDK4 degradation in response to the cardiac metabolic environment. We found that PDK4 degradation is promoted by CoA (CoASH), the levels of which declined in mice fed a high-fat diet and normalized following transition to a control diet. We conclude that CoASH functions as a metabolic sensor linking the rate of PDK4 degradation to fatty acid availability in the heart. However, prolonged high-fat feeding followed by return to a low-fat diet resulted in persistent
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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.