ArticleRedox biology2019
FoxO6-mediated IL-1β induces hepatic insulin resistance and age-related inflammation via the TF/PAR2 pathway in aging and diabetic mice.
Article in Redox biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 47 citations in OpenAlex.
- Increased WNT10B/FOXO6 signaling promotes cell fate transition in renal tubular cells to aggravate renal inflammation and fibrosis.Nature communications · 2026Article
- Resistance exercise and skeletal muscle: protein synthesis, degradation, and controversies.European journal of applied physiology · 2025Review
- The Role of PAR2 in MASLD Progression and HCC Development.International journal of molecular sciences · 2025Review
- Stem cell-based therapeutic strategies for liver aging.Liver research (Beijing, China) · 2025Review
- Systematic mining and quantification reveal the dominant contribution of non-HLA variations to acute graft-versus-host disease.Cellular & molecular immunology · 2025Article
- Astragalin relieves inflammatory pain and negative mood in CFA mice by down-regulating mGluR5 signaling pathway.Scientific reports · 2025Article
- Interplay Between Insulin Resistance and Immune Dysregulation in Type 2 Diabetes Mellitus: Implications for Therapeutic Interventions.ImmunoTargets and therapy · 2025Review
- MicroRNA-7 deficiency ameliorates d-galactose-induced aging in mice by regulating senescence of Kupffer cells.Aging cell · 2024Article
- Article
- FoxO6-Mediated TXNIP Induces Lipid Accumulation in the Liver through NLRP3 Inflammasome Activation.Endocrinology and metabolism (Seoul, Korea) · 2024Article
- Increased IL-1β in stratum corneum as a marker of inflammation among central centrifugal cicatricial alopecia patients with pruritus: An observational study.JAAD international · 2023Article
- Modeling and therapeutic targeting of inflammation-induced hepatic insulin resistance using human iPSC-derived hepatocytes and macrophages.Nature communications · 2023Article
- Glucose-driven transformable complex eliminates biofilm and alleviates inflamm-aging for diabetic periodontitis therapy.Materials today. Bio · 2023Article
- Impact of Dietary Fiber on Inflammation and Insulin Resistance in Older Patients: A Narrative Review.Nutrients · 2023Review
- Resolving the conflicts around Par2 opposing roles in regeneration by comparing immune-mediated and toxic-induced injuries.Inflammation and regeneration · 2022Article
- KYA1797K, a Novel Small Molecule Destabilizing β-Catenin, Is Superior to ICG-001 in Protecting against Kidney Aging.Kidney diseases (Basel, Switzerland) · 2022Article
- Life without Proteinase Activated Receptor 2 (PAR2) Alters Body Composition and Glucose Tolerance in Mice.Nutrients · 2022Article
- Intestinal aging is alleviated by uridine via regulating inflammation and oxidative stressCell cycle (Georgetown, Tex.) · 2022Article
- Malnutrition is positively associated with cognitive decline in centenarians and oldest-old adults: A cross-sectional study.EClinicalMedicine · 2022Article
- Renal tubular PAR2 promotes interstitial fibrosis by increasing inflammatory responses and EMT process.Archives of pharmacal research · 2022Article
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
FoxO has been proposed to play a role in the promotion of insulin resistance, and inflammation. FoxO is a pro-inflammatory transcription factor that is a key mediator of generation of inflammatory cytokines such as IL-1β in the liver. However, the detailed association of FoxO6 with insulin resistance and age-related inflammation has not been fully documented. Here, we showed that FoxO6 was elevated in the livers of aging rats and obese mice that exhibited insulin resistance. In addition, virus-mediated FoxO6 activation led to insulin resistance in mice with a notable increase in PAR2 and inflammatory signaling in the liver. On the other hand, FoxO6-KO mice showed reduced PAR2 signaling with a decrease in inflammatory cytokine expression and elevated insulin signaling. Because FoxO6 is closely associated with abnormal production of IL-1β in the liver, we focused on the FoxO6/IL-1β/PAR2 axis to further examine mechanisms underlying FoxO6-mediated insulin resistance and inflammation in the liver. In vitro experiments showed that FoxO6 directly binds to and elevates IL-1β expression. In turn, IL-1β treatment elevated the protein levels of PAR2 with a significant decrease in hepatic insulin signaling, whereas PAR2-siRNA treatment abolished these effects. However, PAR2-siRNA treatment had no effect on IL-1β expression induced by FoxO6, indicating that IL-1β may not be downstream of PAR2. Taken together, we assume that FoxO6-mediated IL-1β is involved in hepatic inflammation and insulin resistance via TF/PAR2 pathway in the liver.
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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.