ArticleInflammation research : official journal of the European Histamine Research Society ... [et al.]2012
FOXO1 involvement in insulin resistance-related pro-inflammatory cytokine production in hepatocytes.
Article in Inflammation research : official journal of the European Histamine Research Society ... [et al.], 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 36 citations in OpenAlex.
- Cellular signaling crosstalk between osteoporosis and diabetes: Common mechanisms and therapeutic targets (Review).Biomedical reports · 2026Review
- Signaling pathways and targeted therapeutic strategies for polycystic ovary syndrome.Frontiers in endocrinology · 2023Review
- Obesity, non-alcoholic fatty liver disease and hepatocellular carcinoma: current status and therapeutic targets.Frontiers in endocrinology · 2023Review
- TNF-Oxidative medicine and cellular longevity · 2022Article
- Pathophysiological communication between hepatocytes and non-parenchymal cells in liver injury from NAFLD to liver fibrosis.Advanced drug delivery reviews · 2021Review
- Involvement of Transcription Factor FoxO1 in the Pathogenesis of Polycystic Ovary Syndrome.Frontiers in physiology · 2021Review
- Targeted Inhibition of FTO Demethylase Protects Mice Against LPS-Induced Septic Shock by Suppressing NLRP3 Inflammasome.Frontiers in immunology · 2021Article
- Modulation of hepatic inflammation and energy-sensing pathways in the rat liver by high-fructose diet and chronic stress.European journal of nutrition · 2019Article
- Pathogenesis of and major animal models used for nonalcoholic fatty liver disease.The Journal of international medical research · 2019Review
- FOXO transcription factors in non-alcoholic fatty liver disease.Liver research (Beijing, China) · 2017Article
- Pathogenesis of Nonalcoholic Steatohepatitis.Gastroenterology · 2016Review
- The Mechanism by Which Amentoflavone Improves Insulin Resistance in HepG2 Cells.Molecules (Basel, Switzerland) · 2016Article
- Moderate activation of IKK2-NF-kB in unstressed adult mouse liver induces cytoprotective genes and lipogenesis without apparent signs of inflammation or fibrosis.BMC gastroenterology · 2015Article
- Regulation of forkhead box O1 (FOXO1) by protein kinase B and glucocorticoids: different mechanisms of induction of beta cell death in vitro.Diabetologia · 2013Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveLow-grade inflammation from hepatocytes plays a causal role in hepatic and systemic insulin resistance (IR). We aimed to explore whether and how FOXO1 was involved in IR-related inflammation in hepatocytes.
methodsWe determined FOXO1 expression and activity, insulin and NF-κB signaling, and pro-inflammatory cytokine production in tumor necrosis factor-α (TNF-α)- or dexamethasone (DEX)-induced IR model in vitro and in high fat diet-induced obese or diabetic db/db mice in vivo with quantitative RT-PCR and Western blotting.
resultsWe identified two different but physiologically relevant IR models characterized by attenuated insulin-induced phosphorylation of insulin receptor substrate-1 and AKT in TNF-α- or DEX-treated HepG2 cells. DEX largely increased FOXO1 expression in hepatocytes, while TNF-α did not. Notably, FOXO1 phosphorylation was attenuated in both models. TNF-α-stimulated nuclear translocation of NF-κB (p65) and mRNA levels of interleukin (IL)-1, IL-6 and monocyte attractant protein-1 were partly blocked, while the anti-inflammatory role of DEX was largely potentiated by insulin. FOXO1 knockdown by human-specific FOXO1 small interfering RNA exerted an identical role to insulin. Furthermore, augmented hepatic FOXO1 expression and decreased phosphorylation were found to be associated with elevated pro-inflammatory cytokine production in high fat diet-induced obese and db/db mice.
conclusionFOXO1 potentiates pro-inflammatory cytokine production in insulin-resistant hepatocytes.
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