ArticleEMBO molecular medicine2024
A critical role for HNF4α in polymicrobial sepsis-associated metabolic reprogramming and death.
Article in EMBO molecular medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- 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
- Tissue-selective COPII modulator SEC16B aggravates cardiovascular disease by promoting lipid export.The EMBO journal · 2026Article
- Polymicrobial Sepsis-Induced Changes in Hepatic Stellate Cell Communication in Male C57BL/6J Mice.Cells · 2026Article
- Atorvastatin regulates hepatic transcriptome PXR dependently but distinct from pregnenolone 16α-carbonitrile and does not induce PXR-mediated liver steatosis.Archives of toxicology · 2026Article
- Mitochondria-immunometabolism in sepsis-induced liver injury: mechanisms, biomarkers, and therapeutic opportunities.Frontiers in cellular and infection microbiology · 2026Review
- Linking Metabolic and Mitochondrial Stress to Regulated Cell Death and Inflammatory Organ Injury in Sepsis.Journal of inflammation research · 2026Review
- Sepsis and the Liver.Diseases (Basel, Switzerland) · 2025Review
- Hnf4α integrates AIF and caspase 3/9 signaling to restrict single and coinfecting pathogens in teleosts.PLoS pathogens · 2025Article
- Biological and clinical implications of a model of surveillance immunity.The Journal of clinical investigation · 2025Review
- A crucial role of the malate aspartate shuttle in metabolic reprogramming in TNF-induced SIRS.Frontiers in immunology · 2025Article
- Mechanisms of sepsis-induced acute liver injury: a comprehensive review.Frontiers in cellular and infection microbiology · 2025Review
- HNF4α contributes to hepatic CAR dysfunction in polymicrobial sepsis.Frontiers in immunology · 2025Article
- Comparative Analysis of Hepatic Gene Expression Profiles in Murine and Porcine Sepsis Models.International journal of molecular sciences · 2024Article
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Authors and funding
15 authors.
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Abstract
In sepsis, limited food intake and increased energy expenditure induce a starvation response, which is compromised by a quick decline in the expression of hepatic PPARα, a transcription factor essential in intracellular catabolism of free fatty acids. The mechanism upstream of this PPARα downregulation is unknown. We found that sepsis causes a progressive hepatic loss-of-function of HNF4α, which has a strong impact on the expression of several important nuclear receptors, including PPARα. HNF4α depletion in hepatocytes dramatically increases sepsis lethality, steatosis, and organ damage and prevents an adequate response to IL6, which is critical for liver regeneration and survival. An HNF4α agonist protects against sepsis at all levels, irrespectively of bacterial loads, suggesting HNF4α is crucial in tolerance to sepsis. In conclusion, hepatic HNF4α activity is decreased during sepsis, causing PPARα downregulation, metabolic problems, and a disturbed IL6-mediated acute phase response. The findings provide new insights and therapeutic options in sepsis.
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