TY - JOUR
T1 - Stearidonic and eicosapentaenoic acids inhibit interleukin-6 expression in ob/ob mouse adipose stem cells via toll-like receptor-2-mediated pathways
AU - Hsueh, Hui Wen
AU - Zhou, Zhou
AU - Whelan, Jay
AU - Allen, Kenneth G.D.
AU - Moustaid-Moussa, Naima
AU - Kim, Hyojung
AU - Claycombe, Kate J.
PY - 2011/7/1
Y1 - 2011/7/1
N2 - Increased adipose tissue positively correlates with circulating inflammatory cytokines such as IL-6. We previously reported that adipose stem cells from genetically obese ob/ob mice produce significantly higher levels of IL-6 compared with other cell types such as adipocytes and macrophages within adipose tissue. We also demonstrated that (n-3) PUFA have antiinflammatory effects on adipocyte IL-6 secretion. Based on these findings, we hypothesized that EPA [20:5 (n-3)] and stearidonic acid [SDA, 18:4 (n-3)] would decrease LPS (200 mg/L)-induced IL-6 secretion and IL-6 mRNA content in the adipose stem cells. SDA (100 mmol/L) and EPA (100 mmol/L) significantly reduced LPS-induced IL-6 secretion and decreased IL-6 mRNA expression. To determine the underlying intracellular mechanisms, we tested whether LPS-induced Toll-like-receptor (TLR) 4 and TLR2 expression were modulated by these fatty acids using Western-blot analysis. EPA and SDA suppressed LPS-induced TLR2 but not TLR4 protein expression in the adipose stem cells. Furthermore, SDA and EPA significantly lowered the activation and translocation of NF-kB, a TLR2 downstream signaling target, while protein expression of extracellular signal-regulated kinases-1/2 were unaffected. Collectively, our results suggest that EPA and SDA inhibit LPS-induced IL-6 secretion and IL-6 mRNA expression in the adipose stem cells by decreasing TRL2-mediated signaling pathways.
AB - Increased adipose tissue positively correlates with circulating inflammatory cytokines such as IL-6. We previously reported that adipose stem cells from genetically obese ob/ob mice produce significantly higher levels of IL-6 compared with other cell types such as adipocytes and macrophages within adipose tissue. We also demonstrated that (n-3) PUFA have antiinflammatory effects on adipocyte IL-6 secretion. Based on these findings, we hypothesized that EPA [20:5 (n-3)] and stearidonic acid [SDA, 18:4 (n-3)] would decrease LPS (200 mg/L)-induced IL-6 secretion and IL-6 mRNA content in the adipose stem cells. SDA (100 mmol/L) and EPA (100 mmol/L) significantly reduced LPS-induced IL-6 secretion and decreased IL-6 mRNA expression. To determine the underlying intracellular mechanisms, we tested whether LPS-induced Toll-like-receptor (TLR) 4 and TLR2 expression were modulated by these fatty acids using Western-blot analysis. EPA and SDA suppressed LPS-induced TLR2 but not TLR4 protein expression in the adipose stem cells. Furthermore, SDA and EPA significantly lowered the activation and translocation of NF-kB, a TLR2 downstream signaling target, while protein expression of extracellular signal-regulated kinases-1/2 were unaffected. Collectively, our results suggest that EPA and SDA inhibit LPS-induced IL-6 secretion and IL-6 mRNA expression in the adipose stem cells by decreasing TRL2-mediated signaling pathways.
UR - http://www.scopus.com/inward/record.url?scp=79960326096&partnerID=8YFLogxK
U2 - 10.3945/jn.110.132571
DO - 10.3945/jn.110.132571
M3 - Article
C2 - 21562237
AN - SCOPUS:79960326096
SN - 0022-3166
VL - 141
SP - 1260
EP - 1266
JO - Journal of Nutrition
JF - Journal of Nutrition
IS - 7
ER -