TRAF1 knockdown alleviates palmitate-induced insulin resistance in HepG2 cells through NF-κB pathway

• Published in: Biochemical and biophysical research communications 2015-11, Vol.467 (3), p.527-533
• Main Authors: Zhang, Wanlu, Tang, Zhuqi, Zhu, Xiaohui, Xia, Nana, Zhao, Yun, Wang, Suxin, Cui, Shiwei, Wang, Cuifang
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; ANIMAL TISSUES; Animals; CARBOXYLIC ACIDS; DIABETES MELLITUS; ENZYMES; Gene Knockdown Techniques; GLUCOSE; Hep G2 Cells; Humans; INFLAMMATION; INHIBITION; INSULIN; Insulin Resistance; LIPIDS; LIVER; Liver - drug effects; Liver - metabolism; LIVER CELLS; Male; Mice; Mice, Inbred C57BL; NECROSIS; NEOPLASMS; NF-kappa B - metabolism; NF-κB; Palmitates - pharmacology; PHOSPHORYLATION; RADIOPROTECTIVE SUBSTANCES; RECEPTORS; TNF Receptor-Associated Factor 1 - genetics; TRAF1; Type 2 diabetes
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2015.09.165

High-fat diet (HFD) and inflammation are key contributors to insulin resistance (IR) and Type 2 diabetes mellitus (T2DM). With HFD, plasma free fatty acids (FFAs) can activate the nuclear factor-κB (NF-κB) in target tissues, then initiate negative crosstalk between FFAs and insulin signaling. However, the molecular link between IR and inflammation remains to be identified. We here reported that tumor necrosis factor receptor-associated factor 1 (TRAF1), an adapter in signal transduction, was involved in the onset of IR in hepatocytes. TRAF1 was significantly up-regulated in insulin-resistant liver tissues and palmitate (PA)-treated HepG2 cells. In addition, we showed that depletion of TRAF1 led to inhibition of the activity of NF-κB. Given the fact that the activation of NF-κB played a facilitating role in IR, the phosphorylation of Akt and GSK3β was also analyzed. We found that depletion of TRAF1 markedly reversed PA-induced attenuation of the phosphorylation of Akt and GSK3β in the cells. The accumulation of lipid droplets in hepatocyte and expression of two key gluconeogenic enzymes, PEPCK and G6Pase, were also determined and found to display a similar tendency with the phosphorylation of Akt and GSK3β. Glucose uptake assay indicated that knocking down TRAF1 blocked the effect of PA on the suppression of glucose uptake. These data implicated that TRAF1 knockdown might alleviate PA-induced IR in HepG2 cells through NF-κB pathway. •TRAF1 accelerated PA-induced IR in HepG2 cells mediated through NF-κB signaling.•Knockdown of TRAF1 alleviated PA-induced IR in HepG2 cells.•Knockdown of TRAF1 alleviated PA-induced lipid accumulation in HepG2 cells.•Knockdown of TRAF1 reversed PA-induced suppression of glucose uptake in HepG2 cells.•Knockdown of TRAF1 reversed PA-induced gluconeogenesis in HepG2 cells.