| FOXO1 involvement in insulin resistance-related pro-inflammatory cytokine production in hepatocytes. | |
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MedLine Citation:
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PMID: 22223069 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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OBJECTIVE: Low-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. METHODS: We 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. RESULTS: We 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. CONCLUSION: FOXO1 potentiates pro-inflammatory cytokine production in insulin-resistant hepatocytes. |
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Authors:
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Hongming Miao; Yang Zhang; Zhongyan Lu; Qin Liu; Lixia Gan |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-6 |
Journal Detail:
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Title: Inflammation research : official journal of the European Histamine Research Society ... [et al.] Volume: - ISSN: 1420-908X ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-6 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9508160 Medline TA: Inflamm Res Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Biochemistry and Molecular Biology, The Third Military Medical University, Chongqing, 400038, China, hongming.miao@gmail.com. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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