| Docosahexaenoic acid attenuates macrophage-induced inflammation and improves insulin sensitivity in adipocytes-specific differential effects between LC n-3 PUFA. | |
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MedLine Citation:
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PMID: 22137266 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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OBJECTIVE: Adipose tissue inflammation with immune cell recruitment plays a key role in obesity-induced insulin resistance (IR). Long-chain (LC) n-3 polyunsaturated fatty acids (PUFA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have anti-inflammatory potential; however, their individual effects on adipose IR are ill defined. We hypothesized that EPA and DHA may differentially affect macrophage-induced IR in adipocytes. METHODS: J774.2 macrophages pretreated with EPA or DHA (50 μM for 5 days) were stimulated with lipopolysaccharide (LPS, 100 ng/ml for 30 min-48 h). Cytokine secretion profiles and activation status of macrophages were assessed by enzyme-linked immunosorbent assay and flow cytometry. Pretreated macrophages were seeded onto transwell inserts and placed over 3T3-L1 adipocytes for 24-72 h; effects on adipocyte-macrophage cytokine cross-talk and insulin-stimulated (3)H-glucose transport into adipocytes were monitored. RESULTS: DHA had more potent anti-inflammatory effects relative to EPA, with marked attenuation of LPS-induced nuclear factor (NF)κB activation and tumor necrosis factor (TNF)α secretion in macrophages. DHA specifically enhanced anti-inflammatory interleukin (IL)-10 secretion and reduced the expression of proinflammatory M1 (F4/80(+)/CD11(+)) macrophages. Co-culture of DHA-enriched macrophages with adipocytes attenuated IL-6 and TNFα secretion while enhancing IL-10 secretion. Conditioned media (CM) from DHA-enriched macrophages attenuated adipocyte NFκB activation. Adipocytes co-cultured with DHA-enriched macrophages maintained insulin sensitivity with enhanced insulin-stimulated (3)H-glucose transport, GLUT4 translocation and preservation of insulin-receptor substrate-1 expression compared to co-culture with untreated macrophages. We confirmed that IL-10 expressed by DHA-enriched macrophages attenuates the CM-induced proinflammatory IR phenotype in adipocytes. CONCLUSIONS: We demonstrate an attenuated proinflammatory phenotype of DHA-pretreated macrophages, which when co-cultured with adipocytes partially preserved insulin sensitivity. |
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Authors:
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Elizabeth Oliver; Fiona C McGillicuddy; Karen A Harford; Clare M Reynolds; Catherine M Phillips; Jane F Ferguson; Helen M Roche |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-30 |
Journal Detail:
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Title: The Journal of nutritional biochemistry Volume: - ISSN: 1873-4847 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-12-5 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9010081 Medline TA: J Nutr Biochem Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 Elsevier Inc. All rights reserved. |
Affiliation:
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Nutrigenomics Research Group, UCD Conway Institute, & UCD Institute of Food and Health, University College Dublin, Dublin 4, Ireland; Institute of Molecular Medicine, Trinity Centre for Health Science, Trinity College Dublin, Dublin 8, Ireland. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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