Journal
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
Volume 23, Issue 12, Pages 1661-1667Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jnutbio.2011.11.009
Keywords
PUFA; Arachidonic acid; Eicosapentaenoic acid; Adipocyte; Inflammation; MCP-1; IL-6; Agt
Funding
- USDA National Institute of Food and Agriculture
- NRI [2005-35200-15224]
- University of Tennessee (UT) Center of Excellence in Livestock Diseases and Human Health
- UT Obesity Research Center
- UT AgResearch
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Excessive secretion of proinflammatory adipokines has been linked to metabolic disorders. We have previously documented anti-inflammatory effects of n-3 polyunsaturated fatty acids (n-3 PUFAs) in adipose tissue; however, the mechanisms by which these fatty acids regulate adipokine secretion remain unclear. Here, we determined differential effects of eicosapentaenoic acid (EPA. n-3 PUFA) vs. arachidonic acid (AA, n-6 PUFA) on expression and secretion of angiotensinogen (Agt), interleukin 6 (IL-6) and monocyte chemotactic protein (MCP-1) in 3T3-L1 adipocytes. While both PUFAs increased intracellular Agt protein and mRNA expression. Agt secretion into culture media was increased only by AA treatment, which in turn was prevented by co-treatment with EPA. At various AA/EPA ratios, increasing AA concentrations significantly increased secretion of the above three adipokines, whereas increasing EPA dose-dependently, while lowering AA, decreased their secretion. Moreover, IL-6 and MCP-1 were more significantly reduced by EPA treatment compared to Agt (IL-6>MCP>Agt). Next, we tested whether nuclear factor-kappa B (NF-kappa B), a major proinflammatory transcription factor, was involved in regulation of these adipokines by PUFAs. EPA significantly inhibited NF-kappa B activation compared to control or AA treatments. Moreover, EPA attenuated tumor necrosis factor-alpha-induced MCP-1 and further reduced its secretion in the presence of an NF-kappa B inhibitor. Taken together, we reported here novel beneficial effects of EPA in adipocytes. We demonstrated direct anti-inflammatory effects of EPA, which are at least in part due to the inhibitory effects of this n-3 PUFA on the NF-kappa B pathway in adipocytes. In conclusion, these studies further support beneficial effects of n-3 PUFAs in adipocyte inflammation and metabolic disorders. (C) 2012 Elsevier Inc. All rights reserved.
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