ArticleThe Journal of clinical investigation2022
Myeloid FoxO1 depletion attenuates hepatic inflammation and prevents nonalcoholic steatohepatitis.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Immune-inflammatory biomarkers and immune features in metabolic dysfunction-associated steatotic liver disease: a bibliometric study.Frontiers in immunology · 2026Pooled it
- PDE4D-CXCL13 axis in gland epithelial cells promotes B cell infiltration in primary Sjögren's syndrome.Acta pharmacologica Sinica · 2026Article
- Review
- Epigenetic repression of hepatocyte FoxO1 disrupts local immune homeostasis and promotes liver inflammation.Hepatology (Baltimore, Md.) · 2026Article
- Article
- Unveiling novel macrophage-specific biomarkers in MASH through single-cell sequencing for diagnostic modeling.Journal of lipid research · 2026Article
- Paeoniflorin Alleviates Metabolic Dysfunction-Associated Steatotic Liver Disease by Inhibiting Hepatic Lipogenesis and Inflammation.Inflammation · 2026Article
- Transcutaneous Auricular Vagus Nerve Stimulation Ameliorates Heart Failure with Preserved Ejection Fraction Through Regulating Macrophage Polarization Mediated by Alpha7nAChR.Cardiovascular drugs and therapy · 2026Article
- The Role of Kupffer Cells and Liver Macrophages in the Pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease.Biomedicines · 2026Review
- Studies of Foxo1 over the Past 25 Years: Mechanisms of Insulin Resistance and Glucose Dysregulation.Cells · 2026Review
- Strategies to promote liver fibrosis amelioration with involvement of restorative macrophages.Frontiers in immunology · 2026Review
- Targeting Myeloid FoxO1 Ameliorates Sepsis-induced Intestinal Injury by Modulating Tim4International journal of biological sciences · 2026Article
- GHSR-Foxo1 Signaling in Macrophages Promotes Liver Fibrosis via Inflammatory Response and Hepatic Stellate Cell Activation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Panaxatriol exerts anti-senescence effects and alleviates osteoarthritis and cartilage repair fibrosis by targeting UFL1.Journal of advanced research · 2025Article
- Understanding crosstalk between the gut and liver microbiome: pathogenesis to therapeutic approaches in liver cancer.Cancer cell international · 2025Review
- Hepatocyte FoxO1 depletion exacerbates hepatic inflammation in MASH by targeting cystathionine γ-lyase.Scientific reports · 2025Article
- scCompass: An Integrated Multi-Species scRNA-seq Database for AI-Ready.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Ablation of macrophage transcriptional factor FoxO1 protects against ischemia-reperfusion injury-induced acute kidney injury.Acta pharmaceutica Sinica. B · 2025Article
- Thyroid-Stimulating Hormone: An Important Target for the Prevention of Nonalcoholic Fatty Liver Disease.Physiological research · 2025Review
- Identification of IL-34 and Slc7al as potential key regulators in MASLD progression through epigenomic profiling.Epigenomics · 2025Article
Corrections and comments
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Authors and funding
20 authors at 3 institutions in 2 countries.
Funding
Abstract
Hepatic inflammation is culpable for the evolution of asymptomatic steatosis to nonalcoholic steatohepatitis (NASH). Hepatic inflammation results from abnormal macrophage activation. We found that FoxO1 links overnutrition to hepatic inflammation by regulating macrophage polarization and activation. FoxO1 was upregulated in hepatic macrophages, correlating with hepatic inflammation, steatosis, and fibrosis in mice and patients with NASH. Myeloid cell conditional FoxO1 knockout skewed macrophage polarization from proinflammatory M1 to the antiinflammatory M2 phenotype, accompanied by a reduction in macrophage infiltration in liver. These effects mitigated overnutrition-induced hepatic inflammation and insulin resistance, contributing to improved hepatic metabolism and increased energy expenditure in myeloid cell FoxO1-knockout mice on a high-fat diet. When fed a NASH-inducing diet, myeloid cell FoxO1-knockout mice were protected from developing NASH, culminating in a reduction in hepatic inflammation, steatosis, and fibrosis. Mechanistically, FoxO1 counteracts Stat6 to skew macrophage polarization from M2 toward the M1 signature to perpetuate hepatic inflammation in NASH. FoxO1 appears to be a pivotal mediator of macrophage activation in response to overnutrition and a therapeutic target for ameliorating hepatic inflammation to stem the disease progression from benign steatosis to NASH.
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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.