ArticleCell metabolism2017
Defective Branched-Chain Amino Acid Catabolism Disrupts Glucose Metabolism and Sensitizes the Heart to Ischemia-Reperfusion Injury.
Article in Cell metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 249 papers, 3 of them syntheses that pooled it.
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
249 citing papers in PubMed, 3 syntheses or guidelines pooled it, 414 citations in OpenAlex.
- Serum branched amino acids and the risk of all-cause mortality: a meta-analysis and systematic review.Amino acids · 2023Pooled it
- Sarcopenia and cardiovascular diseases: A systematic review and meta-analysis.Journal of cachexia, sarcopenia and muscle · 2023Pooled it
- Genome-wide association and multi-trait analyses characterize the common genetic architecture of heart failure.Nature communications · 2022Pooled it
- Trial
- A randomized placebo-controlled clinical trial for pharmacological activation of BCAA catabolism in patients with type 2 diabetes.Nature communications · 2022Trial
- Article
- Cyclic azapeptide CD36 ligand attenuates cardiac injury and reduces long-chain fatty acid accumulation after myocardial ischemia-reperfusion in mice.FEBS open bio · 2026Article
- Ambient Temperature Preservation Supports Recovery of Beating Capacity in Human Cardiac Organoids After Exposure to Simulated Space Stressors.International journal of molecular sciences · 2026Article
- Amino Acid Metabolism in Health and Disease.MedComm · 2026Review
- Differential transcriptomic and metabolomic landscape between human hearts donated after cardiac vs brain death.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2026Article
- RND3 Enhances Cardiac Glucose Metabolism Through Inhibiting ACAT1-Dependent PDHA1 Acetylation and Protects Against Ischemia-Reperfusion Injury.Circulation · 2026Article
- ACAD8 deficiency promotes pathological cardiac hypertrophy in response to pressure overload by regulating histone isobutyrylation.Nature communications · 2026Article
- Dietary intake and BCAA metabolism regulate pulmonary fibrosis through KDM4A-mediated epigenetic remodeling in male mice.Nature communications · 2026Article
- Lactylation and acetylation: parallel paths, divergent deeds, and research dilemmas.Journal of translational medicine · 2026Review
- Regulation of pyruvate dehydrogenase complex: Dancing to different drums in cancer.International journal of cancer · 2026Review
- Defects in auxiliary fuel oxidation and mitochondrial pyruvate transport mark transition to overt heart failure in Tgαq*44 mice.Journal of translational medicine · 2026Article
- Branched-chain α-keto acids impair glucose-stimulated insulin secretion in pancreatic β-cells under diabetes by reactivating the LDHA-lactate axis.Nature communications · 2026Article
- The Association Between Metabolomic and Usual Biochemical Data Helps to Detect Insulin Resistance.Biomedicines · 2026Article
- Article
- Plasma and pericardial fluid metabolomic signatures of patients with ischemic heart disease.Communications medicine · 2026Article
189 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
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Elevated levels of branched-chain amino acids (BCAAs) have recently been implicated in the development of cardiovascular and metabolic diseases, but the molecular mechanisms are unknown. In a mouse model of impaired BCAA catabolism (knockout [KO]), we found that chronic accumulation of BCAAs suppressed glucose metabolism and sensitized the heart to ischemic injury. High levels of BCAAs selectively disrupted mitochondrial pyruvate utilization through inhibition of pyruvate dehydrogenase complex (PDH) activity. Furthermore, downregulation of the hexosamine biosynthetic pathway in KO hearts decreased protein O-linked N-acetylglucosamine (O-GlcNAc) modification and inactivated PDH, resulting in significant decreases in glucose oxidation. Although the metabolic remodeling in KO did not affect baseline cardiac energetics or function, it rendered the heart vulnerable to ischemia-reperfusion injury. Promoting BCAA catabolism or normalizing glucose utilization by overexpressing GLUT1 in the KO heart rescued the metabolic and functional outcome. These observations revealed a novel role of BCAA catabolism in regulating cardiac metabolism and stress response.
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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.