n-3 and n-6 polyunsaturated fatty acids differentially regulate adipose angiotensinogen and other inflammatory adipokines in part via NF-κB-dependent mechanisms

J Nutr Biochem. 2012 Dec;23(12):1661-7. doi: 10.1016/j.jnutbio.2011.11.009. Epub 2012 Apr 3.


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-κB (NF-κB), a major proinflammatory transcription factor, was involved in regulation of these adipokines by PUFAs. EPA significantly inhibited NF-κB activation compared to control or AA treatments. Moreover, EPA attenuated tumor necrosis factor-α-induced MCP-1 and further reduced its secretion in the presence of an NF-κB 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-κB pathway in adipocytes. In conclusion, these studies further support beneficial effects of n-3 PUFAs in adipocyte inflammation and metabolic disorders.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / drug effects
  • Adipocytes / metabolism
  • Adipokines / metabolism*
  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism
  • Angiotensinogen / metabolism*
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Arachidonic Acid / pharmacology*
  • Cell Differentiation / drug effects
  • Chemokine CCL2 / metabolism
  • Diet, High-Fat / adverse effects
  • Eicosapentaenoic Acid / pharmacology*
  • Inflammation / metabolism
  • Interleukin-6 / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism*


  • Adipokines
  • Anti-Inflammatory Agents, Non-Steroidal
  • Ccl2 protein, mouse
  • Chemokine CCL2
  • Interleukin-6
  • NF-kappa B
  • Angiotensinogen
  • Arachidonic Acid
  • Eicosapentaenoic Acid