| Lack of Interleukin-1 Receptor I (IL-1RI) Protects Mice From High-Fat Diet-Induced Adipose Tissue Inflammation Coincident With Improved Glucose Homeostasis. | |
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MedLine Citation:
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PMID: 21515850 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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OBJECTIVE High-fat diet (HFD)-induced adipose tissue inflammation is a critical feature of diet-induced insulin resistance (IR); however, the contribution of interleukin-1 receptor I (IL-1RI)-mediated signals to this phenotype has not been defined. We hypothesized that lack of IL-1RI may ameliorate HFD-induced IR by attenuating adipose tissue inflammation. RESEARCH DESIGN AND METHODS Glucose homeostasis was monitored in chow- and HFD-fed wild-type (WT) and IL-1RI(-/-) mice by glucose tolerance and insulin tolerance tests. Macrophage recruitment and cytokine signature of adipose tissue macrophages was evaluated. Insulin sensitivity and cytokine secretion from adipose explants was quantified. Cytokine secretion and adipocyte insulin sensitivity was measured in cocultures of WT or IL-1RI(-/-) macrophages with 3T3L1 adipocytes. Synergistic effects of IL-1β with tumor necrosis factor (TNF)-α on inflammation was monitored in WT and IL-1RI(-/-) bone-marrow macrophages and adipose explants. RESULTS Lean and obese IL-1RI(-/-) animals exhibited enhanced glucose homeostasis by glucose tolerance test and insulin tolerance test. M1/M2 macrophage number in adipose tissue was comparable between genotypes; however, TNF-α and IL-6 secretion was lower from IL-1RI(-/-) adipose tissue macrophages. IL-1RI(-/-) adipose exhibited enhanced insulin sensitivity, elevated pAKT, lower cytokine secretion, and attenuated induction of phosphorylated STAT3 and suppressor of cytokine signaling molecule 3 after HFD. Coculture of WT, but not IL-1RI(-/-) macrophages, with 3T3L1 adipocytes enhanced IL-6 and TNF-α secretion, reduced adiponectin secretion, and impaired adipocyte insulin sensitivity. TNF-α and IL-1β potently synergized to enhance inflammation in WT macrophages and adipose, an effect lost in the absence of IL-1RI. CONCLUSIONS Lack of IL-1RI protects against HFD-induced IR coincident with reduced local adipose tissue inflammation, despite equivalent immune cell recruitment. |
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Authors:
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Fiona C McGillicuddy; Karen A Harford; Clare M Reynolds; Elizabeth Oliver; Mandy Claessens; Kingston H G Mills; Helen M Roche |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-4-22 |
Journal Detail:
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Title: Diabetes Volume: - ISSN: 1939-327X ISO Abbreviation: - Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-4-25 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372763 Medline TA: Diabetes Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Nutrigenomics Research Group, University College Dublin Conway Institute, School of Public Health & Population Science, University College Dublin, Dublin, Ireland. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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