ArticleJCI insight2022
Dichloroacetate improves systemic energy balance and feeding behavior during sepsis.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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
18 citing papers in PubMed, 28 citations in OpenAlex.
- Imeglimin pretreatment improves survival and attenuates sepsis-associated acute kidney injury following Escherichia coli challenge in diabetic mice.Clinical and experimental nephrology · 2026Article
- Article
- Therapeutic Targets for Hepatic Fibrosis Driven by Hypoxia-Mediated Hepatic Stellate Cell Activation.Biomolecules · 2026Review
- Evaluating skeletal muscle dysfunction and recovery in a zymosan model of critical illness in mice.Disease models & mechanisms · 2026Article
- Mitochondria-immunometabolism in sepsis-induced liver injury: mechanisms, biomarkers, and therapeutic opportunities.Frontiers in cellular and infection microbiology · 2026Review
- Progress on the correlation between sepsis and gut microbiota: a narrative review.Frontiers in microbiology · 2026Review
- Sepsis and the Liver.Diseases (Basel, Switzerland) · 2025Review
- Evaluating skeletal muscle wasting and weakness in models of critical illness.Clinical science (London, England : 1979) · 2025Review
- Dichloroacetate Prevents Sepsis Associated Encephalopathy by Inhibiting Microglia Pyroptosis through PDK4/NLRP3.Inflammation · 2025Article
- Comparative metabolomic analysis reveals shared and unique features of COVID-19 cytokine storm and surgical sepsis.Scientific reports · 2025Article
- The pyruvate dehydrogenase kinase inhibitor dichloroacetate mitigates alcohol-induced hepatic inflammation and metabolic disturbances in mice.Hepatology communications · 2024Article
- Sepsis-induced changes in pyruvate metabolism: insights and potential therapeutic approaches.EMBO molecular medicine · 2024Review
- Metabolic Regulation in the Induction of Trained Immunity.Seminars in immunopathology · 2024Review
- Article
- The Values of PDK1 and LDH Levels in Patients with Sepsis and Septic Shock: A Prospective Observational Study.Journal of inflammation research · 2024Article
- Regulating mitochondrial metabolism by targeting pyruvate dehydrogenase with dichloroacetate, a metabolic messenger.Biochimica et biophysica acta. Molecular basis of disease · 2023Review
- Glutathionylation of pyruvate dehydrogenase complex E2 and inflammatory cytokine production during acute inflammation are magnified by mitochondrial oxidative stress.Redox biology · 2023Article
- Pyruvate dehydrogenase kinase supports macrophage NLRP3 inflammasome activation during acute inflammation.Cell reports · 2023Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Sepsis is a life-threatening organ dysfunction caused by dysregulated host response to an infection. The metabolic aberrations associated with sepsis underly an acute and organism-wide hyperinflammatory response and multiple organ dysfunction; however, crosstalk between systemic metabolomic alterations and metabolic reprogramming at organ levels remains unknown. We analyzed substrate utilization by the respiratory exchange ratio, energy expenditure, metabolomic screening, and transcriptional profiling in a cecal ligation and puncture model to show that sepsis increases circulating free fatty acids and acylcarnitines but decreases levels of amino acids and carbohydrates, leading to a drastic shift in systemic fuel preference. Comparative analysis of previously published metabolomics from septic liver indicated a positive correlation with hepatic and plasma metabolites during sepsis. In particular, glycine deficiency was a common abnormality of the plasma and liver during sepsis. Interrogation of the hepatic transcriptome in septic mice suggested that the septic liver may contribute to systemic glycine deficiency by downregulating genes involved in glycine synthesis. Interestingly, intraperitoneal injection of the pyruvate dehydrogenase kinase (PDK) inhibitor dichloroacetate reversed sepsis-induced anorexia, energy imbalance, inflammation, dyslipidemia, hypoglycemia, and glycine deficiency. Collectively, our data indicated that PDK inhibition rescued systemic energy imbalance and metabolic dysfunction in sepsis partly through restoration of hepatic fuel metabolism.
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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.