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Docosahexaenoic acid decreases pro-inflammatory mediators in an in vitro murine adipocyte macrophage co-culture model

PLoS ONE, ISSN: 1932-6203, Vol: 9, Issue: 1, Page: e85037
2014
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Proinflammatory effects of arachidonic acid in a lipopolysaccharide-induced inflammatory microenvironment in 3T3-L1 adipocytes in vitro

  Introduction            Adipose tissue is an active endocrine organ that secretes a plethora of proteins, collectively called adipokines, which play a critical role in modulating systemic

Article Description

Paracrine interactions between adipocytes and macrophages contribute to chronic inflammation in obese adipose tissue. Dietary strategies to mitigate such inflammation include long-chain polyunsaturated fatty acids, docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids, which act through PPARγ-dependent and independent pathways. We utilized an in vitro co-culture model designed to mimic the ratio of macrophages:adipocytes in obese adipose tissue, whereby murine 3T3-L1 adipocytes were cultured with RAW 264.7 macrophages in direct contact, or separated by a trans-well membrane (contact-independent mechanism), with 125 μM of albumin-complexed DHA, EPA, palmitic acid (PA), or albumin alone (control). Thus, we studied the effect of physical cell contact versus the presence of soluble factors, with or without a PPARγ antagonist (T0070907) in order to elucidate putative mechanisms. After 12 hr, DHA was the most anti-inflammatory, decreasing MCP1 and IL-6 secretion in the contact system (-57%, -63%, respectively, p≤0.05) with similar effects in the trans-well system. The trans-well system allowed for isolation of cell types for inflammatory mediator analysis. DHA decreased mRNA expression (p<0.05) of Mcp1 (-7.1 fold) and increased expression of the negative regulator, Mcp1-IP (+1.5 fold). In macrophages, DHA decreased mRNA expression of pro-inflammatory M1 polarization markers (p≤0.05), Nos2 (iNOS; -7 fold), Tnfα (-4.2 fold) and Nfκb (-2.3 fold), while increasing anti-inflammatory Tgfβ1 (+1.7 fold). Interestingly, the PPARγ antagonist co-administered with DHA or EPA in co-culture reduced (p≤0.05) adiponectin cellular protein, without modulating other cytokines (protein or mRNA). Overall, our findings suggest that DHA may lessen the degree of MCP1 and IL-6 secreted from adipocytes, and may reduce the degree of M1 polarization of macrophages recruited to adipose tissue, thereby decreasing the intensity of pro-inflammatory cross-talk between adipocytes and macrophages in obese adipose tissue. © 2014 De Boer et al.

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http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84908304356&origin=inward; http://dx.doi.org/10.1371/journal.pone.0085037; http://www.ncbi.nlm.nih.gov/pubmed/24465472; https://dx.plos.org/10.1371/journal.pone.0085037.t001; http://dx.doi.org/10.1371/journal.pone.0085037.t001; https://dx.plos.org/10.1371/journal.pone.0085037.g004; http://dx.doi.org/10.1371/journal.pone.0085037.g004; https://dx.plos.org/10.1371/journal.pone.0085037.g003; http://dx.doi.org/10.1371/journal.pone.0085037.g003; https://dx.plos.org/10.1371/journal.pone.0085037.g001; http://dx.doi.org/10.1371/journal.pone.0085037.g001; https://dx.plos.org/10.1371/journal.pone.0085037.g005; http://dx.doi.org/10.1371/journal.pone.0085037.g005; https://dx.plos.org/10.1371/journal.pone.0085037.g002; http://dx.doi.org/10.1371/journal.pone.0085037.g002; https://dx.plos.org/10.1371/journal.pone.0085037; https://dx.doi.org/10.1371/journal.pone.0085037; https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0085037; https://dx.doi.org/10.1371/journal.pone.0085037.g002; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0085037.g002; https://dx.doi.org/10.1371/journal.pone.0085037.g001; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0085037.g001; https://dx.doi.org/10.1371/journal.pone.0085037.g003; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0085037.g003; https://dx.doi.org/10.1371/journal.pone.0085037.g005; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0085037.g005; https://dx.doi.org/10.1371/journal.pone.0085037.g004; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0085037.g004; https://dx.doi.org/10.1371/journal.pone.0085037.t001; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0085037.t001; http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0085037; https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0085037&type=printable; http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0085037; http://dx.plos.org/10.1371/journal.pone.0085037.t001; http://dx.plos.org/10.1371/journal.pone.0085037.g004; http://dx.plos.org/10.1371/journal.pone.0085037.g003; http://dx.plos.org/10.1371/journal.pone.0085037; http://www.plosone.org/article/metrics/info:doi/10.1371/journal.pone.0085037; http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0085037&type=printable; http://dx.plos.org/10.1371/journal.pone.0085037.g001; http://dx.plos.org/10.1371/journal.pone.0085037.g005; http://dx.plos.org/10.1371/journal.pone.0085037.g002

Anna A. De Boer; Jennifer M. Monk; Lindsay E. Robinson; Gernot Zissel

Public Library of Science (PLoS)

Biochemistry, Genetics and Molecular Biology; Agricultural and Biological Sciences; Multidisciplinary

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