|Hsueh, Hui -|
|Zhou, Zhou -|
|Whelan, Jay -|
|Allen, Kenneth -|
|Moustaid-Moussa, Naima -|
|Kim, Hyojung -|
Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: April 5, 2011
Publication Date: July 1, 2011
Citation: Hsueh, H.W., Zhou, Z., Whelan, J., Allen, K.G., Moustaid-Moussa, N., Kim, H., Claycombe, K.J. 2011. Stearidonic and eicosapentaenoic acids inhibit interleukin-6 expression in ob/ob mouse adipose stem cells via toll-like receptor-2-mediated pathways. Journal of Nutrition. 141:1260-1266. Interpretive Summary: Several recent studies have demonstrated the beneficial effects of n-3 polyunsaturated fatty acids (PUFA) in lowering heart disease risks by lowering body’s inflammation. Fat tissue has been shown to produce significant amount of inflammatory factor interleukin-6 (IL-6). IL-6 is a key activator of C-reactive protein (CRP) which is a major CVD risk biomarker and one of the major causes of CVD. Thus, it is plausible that one of the mechanisms in which n-3 PUFAs could reduce CVD risk may be by decreasing lowering inflammatory factor such as IL-6. Moreover, it has been shown that fat tissue contributes significantly toward overall increases in serum IL-6 in obesity. We previously showed adipose stem cell produce significantly higher levels of IL-6 when compared to other cell types in the adipose tissue in genetically obese mice. Using these highly inflammatory adipose stem cells that were derived from adipose tissue, we tested inhibitory effects of n-3 PUFAs on lipopolysaccharide (LPS)-induced IL-6 secretion. Data obtained from our studies showed that omega-3 fats such as eicosapentaenoic acid (EPA, 20:5 n-3) and EPA precursor stearidonic acid (SDA. 18:4 n-3) significantly reduce inflammatory factor (IL-6) secretion. We determine the underlying cellular mechanisms to be via decreased activation of Toll-like-receptor 2 (TLR2) and by decreasing activation of gene expression regulator NF-kB. Our work is first to investigate the anti-inflammatory effects of omega-3 fats using adipose stem cells. This research project will impact how fat tissue inflammatory responses can be regulated by decreasing fat tissue stem cell production of inflammatory factors.
Technical Abstract: Increases in adipose tissue weight positively correlates with increased circulating inflammatory cytokines such as interleukin-6 (IL-6). We previously have shown that adipose stem cell produce significantly higher levels of IL-6 when compared to other cell types in the adipose tissue in genetically obese mice. Using these highly inflammatory adipose stem cells that were derived from adipose tissue, we tested whether n-3 polyunsaturated fatty acids (n-3 PUFA) such as eicosapentaenoic acid (EPA, 20:5 n-3) and EPA precursor stearidonic acid (SDA, 18:4 n-3) have IL-6 lowering effects. Results showed that both SDA and EPA significantly reduce LPS-induced IL-6 secretion and IL-6 mRNA. To determine the underlying intracellular mechanisms, we tested whether LPS-induced Toll-like-receptor 4 (TLR4) and Toll-like-receptor 2 (TLR2) expression are modulated with EPA and SDA treatment. Our results showed that both EPA and SDA suppress LPS-induced TLR2 protein expression in the adipose stem cells while SDA and EPA had no effects on TLR4 expression. Furthermore, our results showed that SDA and EPA significantly lower the activation and translocation of TLR2 downstream signaling pathway such nuclear factor-kappa B (NF-'B) while extracellular signal-regulated kinase-1/2 MAPK (ERK-1/2) protein expressions were not affected. Taken together, our results suggest that EPA and SDA inhibit the LPS-induced IL-6 secretion and IL-6 mRNA expression in the adipose stem cells by decreasing TRL2 mediated signaling pathways.