Fucoidan Ameliorates TNFα-induced Insulin Resistance by Inhibiting SOCS3, JNK Activation and IκBα Degradation in 3T3-L1 Adipocytes

다국어 초록 (Multilingual Abstract)

Obesity is a major factor causing insulin resistance in patients with type 2 diabetes. In adipocytes, overly expressed tumor necrosis factor-alpha (TNFα), due to obesity, is critical in developing insulin resistance. Fucoidan is a sulfated polysaccharide found in brown seaweeds that is known to have various biological properties. The purpose of this study was to investigate the effects of fucoidan on ameliorating TNFα-induced insulin resistance in 3T3-L1 cells to test the hypothesis that fucoidan exerts an increasing glucose uptake on adipocytes. In TNFα-treated 3T3-L1 adipocytes, fucoidan significantly increased glucose uptake in a dose-dependent manner. Fucoidan significantly reduced the expression of suppressor of cytokine signaling-3 (SOCS3), a negative regulator of insulin signaling, and the phosphorylation of c-Jun N-terminal kinase (JNK), a serine kinase in the inflammatory pathways within insulin target cells. It also significantly decreased proteosomal degradation of inhibitor of κB alpha (IκBα). Consequently, fucoidan reduced serine phosphorylation and increased tyrosine phosphorylation of IRS-1, which was followed by increased phosphoinositide 3-kinase (PI3K) activation and protein kinase B (AKT) phosphorylation, thereby increasing glucose uptake via intracellular glucose Transporter Type 4 (GLUT4) translocation to the plasma membrane. In summary, fucoidan can potently suppress TNFα-induced insulin resistance by inhibiting activation of SOCS3, JNK and degradation of IκBα in 3T3-L1 adipocytes. These results suggest that the potential of fucoidan in improving inflammatory conditions and insulin resistance in adipocytes.