ArticleEMBO molecular medicine2020
Hepatic PPARα function and lipid metabolic pathways are dysregulated in polymicrobial sepsis.
Article in EMBO molecular medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 67 citations in OpenAlex.
- Hepatocyte HNF4α Deficiency Protects Against Pneumococcal Sepsis Through a Neutrophil-Dependent Mechanism.International journal of molecular sciences · 2026Article
- RXRα suppression drives hepatic metabolic and immune dysfunction in sepsis.EMBO molecular medicine · 2026Article
- Macrophage metabolism reprogramming in sepsis: Pathogenesis and therapeutic implications (Review).International journal of molecular medicine · 2026Review
- Polymicrobial Sepsis-Induced Changes in Hepatic Stellate Cell Communication in Male C57BL/6J Mice.Cells · 2026Article
- PPARα: Linking Cardiac Metabolism to Therapeutic Opportunities in Cardiovascular Diseases.Cells · 2026Review
- Lipopolysaccharides Drive Proinflammatory Extracellular Vesicle Secretion in Coronary Artery Endothelial Cells via Noncanonical Inflammasome Activation.Cellular and molecular life sciences : CMLS · 2026Article
- Plasma Linoleic Acid Is Associated With Pediatric Sepsis Phenotype and Acute Kidney Injury.Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies · 2026Article
- Lactylation as a metabolic-epigenetic switch: Mechanisms and roles in cancer, sepsis, trauma, inflammation, and tissue repair.Biochemistry and biophysics reports · 2026Review
- Sepsis and the immunometabolic inflammatory response.npj metabolic health and disease · 2026Review
- Baihe Gujin decoction ameliorates sepsis-induced acute lung injury through Nrf2/GPX4-mediated antioxidant defense and PPARα-driven metabolic reprogramming: a multi-omics investigation.Frontiers in immunology · 2026Article
- Metabolic Reprogramming and Immune Metabolism in Sepsis: Targeting the PPAR Pathway for Personalized Therapeutic Approaches.PPAR research · 2026Review
- Diagnostic and Prognostic Biomarkers for Sepsis-Associated Liver Injury: Current Status and Future Perspectives.Gastroenterology research and practice · 2026Review
- Machine Learning-Guided Multi-Omics Integration Identifies UGCG as a Candidate Lipid Metabolic Biomarker and Potential Therapeutic Target in Sepsis.Journal of inflammation research · 2026Article
- Mitochondria-immunometabolism in sepsis-induced liver injury: mechanisms, biomarkers, and therapeutic opportunities.Frontiers in cellular and infection microbiology · 2026Review
- Regulated cell death in sepsis-associated liver injury: molecular mechanisms and therapeutic implications.Frontiers in immunology · 2026Review
- Branched-chain amino acids and sepsis: from pathological mechanisms to clinical interventions.Nutrition & metabolism · 2025Review
- Ketogenic Nutrition in Combination With PPARα Activation Induced Metabolic Failure and Exacerbated Muscle Weakness in Septic Mice.Journal of cachexia, sarcopenia and muscle · 2025Article
- Sepsis and the Liver.Diseases (Basel, Switzerland) · 2025Review
- Angiopoietin-like protein 8 orchestrates macrophage glycogen metabolism and polarization via the JNK signaling pathway in cytokine storm syndrome.Cell & bioscience · 2025Article
- The Overlapping Biology of Sepsis and Cancer and Therapeutic Implications.Biomedicines · 2025Review
Corrections and comments
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Authors and funding
20 authors at 4 institutions in 1 country.
Funding
Abstract
Despite intensive research and constant medical progress, sepsis remains one of the most urgent unmet medical needs of today. Most studies have been focused on the inflammatory component of the disease; however, recent advances support the notion that sepsis is accompanied by extensive metabolic perturbations. During times of limited caloric intake and high energy needs, the liver acts as the central metabolic hub in which PPARα is crucial to coordinate the breakdown of fatty acids. The role of hepatic PPARα in liver dysfunction during sepsis has hardly been explored. We demonstrate that sepsis leads to a starvation response that is hindered by the rapid decline of hepatic PPARα levels, causing excess free fatty acids, leading to lipotoxicity, and glycerol. In addition, treatment of mice with the PPARα agonist pemafibrate protects against bacterial sepsis by improving hepatic PPARα function, reducing lipotoxicity and tissue damage. Since lipolysis is also increased in sepsis patients and pemafibrate protects after the onset of sepsis, these findings may point toward new therapeutic leads in sepsis.
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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.