ArticleJournal of molecular and cellular cardiology2015
Metabolomic profiling of the heart during acute ischemic preconditioning reveals a role for SIRT1 in rapid cardioprotective metabolic adaptation.
Article in Journal of molecular and cellular cardiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Metabolic remodeling of substrate utilization during heart failure progression.Heart failure reviews · 2019Pooled it
- Glycation proteomics identifies creatine kinase as a mediator of the effects of methylglyoxal on mitochondrial permeability transition.bioRxiv : the preprint server for biology · 2026Article
- NADMetabolites · 2025Article
- Mass-spectrometry based metabolomics: an overview of workflows, strategies, data analysis and applications.Proteome science · 2025Review
- Suppression of FOXO1 activity by SIRT1-mediated deacetylation weakening the intratumoral androgen autocrine function in glioblastoma.Cancer gene therapy · 2025Article
- MTX2 facilitates PKM2 tetramerization to promote cardiac glucose metabolism and protects the heart against ischemia/reperfusion injury.Theranostics · 2025Article
- Nicotinamide Mononucleotide: Research Process in Cardiovascular Diseases.International journal of molecular sciences · 2024Review
- Autophagic signaling promotes systems-wide remodeling in skeletal muscle upon oncometabolic stress by D2-HG.Molecular metabolism · 2024Article
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- Common mechanistic pathways in cancer and heart failure. A scientific roadmap on behalf of the Translational Research Committee of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC).European journal of heart failure · 2020Article
- AScientific reports · 2020Article
- Long-chain free fatty acids inhibit ischaemic preconditioning of the isolated rat heart.Molecular and cellular biochemistry · 2020Article
- Article
- Cardiac metabolism as a driver and therapeutic target of myocardial infarction.Journal of cellular and molecular medicine · 2020Review
- Oncometabolites in renal cancer.Nature reviews. Nephrology · 2020Review
- Bioenergetics and translational metabolism: implications for genetics, physiology and precision medicine.Biological chemistry · 2019Review
- Tissue-Specific Metabolic Profiles After Prolonged Cardiac Arrest Reveal Brain Metabolome Dysfunction Predominantly After Resuscitation.Journal of the American Heart Association · 2019Article
- Cardioprotection by the mitochondrial unfolded protein response requires ATF5.American journal of physiology. Heart and circulatory physiology · 2019Article
- Aldosterone stimulation mediates cardiac metabolism remodeling via Sirt1/AMPK signaling in canine model.Naunyn-Schmiedeberg's archives of pharmacology · 2019Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Ischemic preconditioning (IPC) protects tissues such as the heart from prolonged ischemia-reperfusion (IR) injury. We previously showed that the lysine deacetylase SIRT1 is required for acute IPC, and has numerous metabolic targets. While it is known that metabolism is altered during IPC, the underlying metabolic regulatory mechanisms are unknown, including the relative importance of SIRT1. Thus, we sought to test the hypothesis that some of the metabolic adaptations that occur in IPC may require SIRT1 as a regulatory mediator. Using both ex-vivo-perfused and in-vivo mouse hearts, LC-MS/MS based metabolomics and (13)C-labeled substrate tracing, we found that acute IPC altered several metabolic pathways including: (i) stimulation of glycolysis, (ii) increased synthesis of glycogen and several amino acids, (iii) increased reduced glutathione levels, (iv) elevation in the oncometabolite 2-hydroxyglutarate, and (v) inhibition of fatty-acid dependent respiration. The majority (83%) of metabolic alterations induced by IPC were ablated when SIRT1 was acutely inhibited with splitomicin, and a principal component analysis revealed that metabolic changes in response to IPC were fundamentally different in nature when SIRT1 was inhibited. Furthermore, the protective benefit of IPC was abrogated by eliminating glucose from perfusion media while sustaining normal cardiac function by burning fat, thus indicating that glucose dependency is required for acute IPC. Together, these data suggest that SIRT1 signaling is required for rapid cardioprotective metabolic adaptation in acute IPC.
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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.