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

• Published in: PloS one 2014-01, Vol.9 (1), p.e85037
• Main Authors: De Boer, Anna A, Monk, Jennifer M, Robinson, Lindsay E
• Format: Article
• Language: English
• Subjects: 3T3-L1 Cells; Adipocytes; Adipocytes - drug effects; Adipocytes - metabolism; Adiponectin; Adipose tissue; Albumin; Animals; Biology; Cell culture; Cell Line; Cellular proteins; Chemokine CCL2 - metabolism; Coculture Techniques; Cytokines; Diabetes; Diet; Docosahexaenoic acid; Docosahexaenoic Acids - pharmacology; Eicosapentaenoic Acid - pharmacology; Fatty acids; Gene expression; Genotype & phenotype; Inflammation; Insulin resistance; Interleukin 6; Interleukin-10 - metabolism; Interleukin-6 - metabolism; Macrophages; Macrophages - drug effects; Macrophages - metabolism; Medicine; Mice; NF-κB protein; Nitric-oxide synthase; Obesity; Omega 3 fatty acids; Palmitic acid; Paracrine signalling; Polarization; Polyunsaturated fatty acids; RNA; Saturated fatty acids; Transforming growth factor-b1; Tumor Necrosis Factor-alpha - metabolism; Type 2 diabetes; Unsaturated fatty acids
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0085037

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