BIOLOGY OF OBESITY PREVENTION
Location: Grand Forks Human Nutrition Research Center
Title: N-3 and n-6 polyunsaturated fatty acids differentially regulate adipose angiotensinogen and other inflammatory adipokines in part via NF-kB dependent mechanisms
| Siriwardhana, Nalin - |
| Kalupahana, Nishan - |
| Fletcher, Sarah - |
| Quignard-Boulange, Annie - |
| Xin, Wenting - |
| Zhao, Ling - |
| Moustaid-Moussa, Naima - |
Submitted to: Journal of Nutritional Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: November 30, 2011
Publication Date: April 3, 2012
Citation: Siriwardhana, N., Kalupahana, N., Fletcher, S., Claycombe, K.J., Quignard-Boulange, A., Xin, W., Zhao, L., Moustaid-Moussa, N. 2012. N-3 and n-6 polyunsaturated fatty acids differentially regulate adipose angiotensinogen and other inflammatory adipokines in part via NF-kB dependent mechanisms. Journal of Nutritional Biochemistry. 23:1661-1667.
Interpretive Summary: Using both cell culture study methods and animal feeding studies, data from our current study demonstrate that n-3 polyunsaturated fatty acid (PUFA) such as eicosapentaenoic acid (EPA) decreases inflammatory cytokine and chemokine secretion and gene expression that are induced by n-6 PUFA such as arachidonic acid (AA) in differentiated adipocytes and in adipose tissues. Our data also showed that these anti-inflammatory effects of EPA are mediated by reduction in transcription factor Nuclear Factor-'B (NF-'B).
Excessive secretion of angiotensinogen (Agt) and other adipokines such as Interleukin-6 (IL-6) and Monocyte chemotactic protein-1 (MCP-1) have been linked to obesity and associated metabolic disorders, with a common feature being inflammation. We have previously shown that n-3 polyunsaturated fatty acids (n-3 PUFAs) exhibit anti-inflammatory properties and modulate adipocyte metabolism. However, mechanisms mediating adipokines regulation by n-3 PUFAs remain unclear. Thus, our goal is to determine differential effects of eicosapentaenoic acid (EPA, n3-PUFA) vs. arachidonic acid (AA, n-6 PUFA) on expression/ secretion of Agt, IL-6 and MCP-1 in 3T3-L1 adipocytes . Secreted Agt was only detectable in culture media of differentiated murine 3T3-L1 adipocytes but not in undifferentiated pre-adipocytes. Both PUFAs increased intracellular Agt mRNA and protein expression. AA significantly increased Agt secretion, while EPA dose-dependently antagonized AA effects. Moreover, EPA dose-dependantly reduced IL-6 and MCP-1 secretion and antagonized AA effects on these cytokines. In vivo high-fat fed C57BL/6J mice supplemented with EPA exhibited significantly reduced Ang II and IL-6 levels in epididymal adipose tissue compared to mice fed with only high-fat diet. Moreover, AA-induced Nuclear Factor-'B (NF-'B) activation was prevented by EPA. Additional pharmacological manipulation of NF-'B confirmed that EPA’s effects on Agt, IL-6 and MCP-1 are mediated at least in part via reduction of NF-'B activation. Taken together, this study demonstrates that EPA imparts its anti-inflammatory activities directly and via antagonism of AA-induced proinflammatory adipokine secretion; and these effects are mediated at least in part by the suppression of NF-'B activation.