ArticleProceedings of the National Academy of Sciences of the United States of America2019
Up-regulation of FOXO1 and reduced inflammation by β-hydroxybutyric acid are essential diet restriction benefits against liver injury.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 118 citations in OpenAlex.
- Epigenetic repression of hepatocyte FoxO1 disrupts local immune homeostasis and promotes liver inflammation.Hepatology (Baltimore, Md.) · 2026Article
- The Role of Gut Microbiota in Liver Regeneration After Partial Hepatectomy: New Evidence From Animal and Human Studies.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- SAA/FPR2 Signaling Between Pericentral Hepatocytes and Macrophages Exacerbates Zonated Liver Transplant Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- β-Hydroxybutyrate upregulates hepatic histone β-hydroxybutyrylation modification, promotes the expression of PPARα, and alleviates the hepatic steatosis in MASLD.Clinical epigenetics · 2026Article
- Role of Histamine in Liver Ischemia-Reperfusion Injury-Implication for H1 Receptor Antagonist in the Clinical Application.Transplantation · 2026Article
- Notch2 Directs aTreg Cell Fate Toward Immunoregulation or Inflammatory Pyroptosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Association between ketone body levels and chronic liver disease: Epidemiological studies and potential mechanisms.AIMS public health · 2026Review
- Sesamin alleviates drug-induced hepatotoxicity via autophagy enhancement and ferroptosis inhibition.Redox report : communications in free radical research · 2025Article
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- Protein modifications in hepatic ischemia-reperfusion injury: molecular mechanisms and targeted therapy.Frontiers in immunology · 2025Review
- Role of novel protein acylation modifications in sepsis.Frontiers in immunology · 2025Review
- β-Hydroxybutyrate enhances chondrocyte mitophagy and reduces cartilage degeneration in osteoarthritis via the HCAR2/AMPK/PINK1/Parkin pathway.Aging cell · 2024Article
- Suppressive Effects of β-Hydroxybutyrate Administration on Lipopolysaccharide-Induced Inflammation in Broiler Chickens.Veterinary sciences · 2024Article
- NLRP3 Inflammasome Inhibitors for Antiepileptogenic Drug Discovery and Development.International journal of molecular sciences · 2024Review
- Pregnane X receptor knockout mitigates weight gain and hepatic metabolic dysregulation in female C57BL/6 J mice on a long-term high-fat diet.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2024Article
- Inhibition of Sodium-Glucose Cotransporter-2 during Serum Deprivation Increases Hepatic Gluconeogenesis via the AMPK/AKT/FOXO Signaling Pathway.Endocrinology and metabolism (Seoul, Korea) · 2024Article
- Impact of fasting & ketogenic interventions on the NLRP3 inflammasome: A narrative review.Biomedical journal · 2024Review
- The therapeutic potential of ketones in cardiometabolic disease: impact on heart and skeletal muscle.American journal of physiology. Cell physiology · 2024Review
- Developing poly(ethylene glycol)-Science and technology of advanced materials · 2024Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Liver ischemia and reperfusion injury (IRI) is a major challenge in liver surgery. Diet restriction reduces liver damage by increasing stress resistance; however, the underlying molecular mechanisms remain unclear. We investigated the preventive effect of 12-h fasting on mouse liver IRI. Partial warm hepatic IRI model in wild-type male C57BL/6 mice was used. The control ischemia and reperfusion (IR) group of mice was given food and water ad libitum, while the fasting IR group was given water but not food for 12 h before ischemic insult. In 12-h fasting mice, serum liver-derived enzyme level and tissue damages due to IR were strongly suppressed. Serum β-hydroxybutyric acid (BHB) was significantly raised before ischemia and during reperfusion. Up-regulated BHB induced an increment in the expression of FOXO1 transcription factor by raising the level of acetylated histone. Antioxidative enzyme heme oxigenase 1 (HO-1), a target gene of FOXO1, then increased. Autophagy activity was also enhanced. Serum high-mobility group box 1 was remarkably lowered by the 12-h fasting, and activation of NF-κB and NLRP3 inflammasome was suppressed. Consequently, inflammatory cytokine production and liver injury were reduced. Exogenous BHB administration or histone deacetylase inhibitor administration into the control fed mice ameliorated liver IRI, while FOXO1 inhibitor administration to the 12-h fasting group exacerbated liver IRI. The 12-h fasting exerted beneficial effects on the prevention of liver IRI by increasing BHB, thus up-regulating FOXO1 and HO-1, and by reducing the inflammatory responses and apoptotic cell death via the down-regulation of NF-κB and NLRP3 inflammasome.
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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.