Effects of paeoniflorin on tumor necrosis factor-α-induced insulin resistance and changes of adipokines in 3T3-L1 adipocytes

Abstract

TNFα plays an important role in the adipocyte dysfunction, including lipolysis acceleration, insulin resistance and changes of adipokines. Recently, we showed that paeoniflorin attenuates adipocyte lipolysis and inhibits the phosphorylation of ERK, JNK, IKK stimulated by TNFα. However, the effects of paeoniflorin on adipocytes insulin resistance and changes of adipokines remain unknown. The aim of the current study was to investigate the role of paeoniflorin in preventing insulin resistance or inflammation in 3T3-L1 adipocytes treated with TNFα. Our results showed that paeoniflorin restored insulin-stimulated [(3)H]2-DOG uptake, which was reduced by TNFα, with concomitant restoration in serine phosphorylation of IRS-1 and insulin-stimulated phosphorylation of AKT in adipocytes. Paeoniflorin attenuated TNFα-mediated suppression of the expressions of PPARγ and PPARγ target genes, and the improvement of paeoniflorin on TNFα-induced insulin resistance was attenuated by GW9662, an antagonist of PPARγ activity. Moreover, paeoniflorin could inhibit the expressions and secretions of IL-6 and MCP-1 from adipocytes induced by TNFα. These results, together with our previous data, indicate that paeoniflorin exerts a beneficial effect on adipocytes to prevent TNFα-induced insulin resistance and inflammatory adipokine release. Our studies provide important evidence for an ability of paeoniflorin in amelioration of TNFα-induced adipocyte dysfunction, which would be helpful to clarify its potential role in the treatment of obesity.

Keywords: AKT; Adipocyte; ERK; I kappaB kinase; IKK; IL-6; IRS-1; Inflammation; Insulin resistance; JNK/SAPK; Jun N-terminal kinase/stress-activated protein kinase; MCP-1; NF-κB; PF; PPARγ; Paeoniflorin; TNFα; Tumor necrosis factor-α; aP2; adipocyte fatty acid-binding protein 2; extracellular signal-regulated kinases; insulin receptor substrate-1; interleukin-6; monocyte chemoattractant protein-1; nuclear factor-κB; paeoniflorin; peroxisome proliferator activated receptor γ; protein kinase B; tumor necrosis factor-α.