Department of Endocrine and Metabolic Diseases, Laboratory of Endocrine and Metabolic Diseases, Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, No.639, Zhizhaoju Road, Shanghai 200211, Shanghai, China.
Yantai Traditional Chinese Medicine Hospital, Affiliated to Shandong University of Traditional Chinese Medicine, No. 39, Xingfu Road, Yantai 264005, Shandong, China.
Fitoterapia. 2013 Dec;91:44-50. doi: 10.1016/j.fitote.2013.08.010. Epub 2013 Aug 23.
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.
TNFα 在脂肪细胞功能障碍中发挥重要作用,包括脂解加速、胰岛素抵抗和脂肪细胞因子的变化。最近,我们发现芍药苷可减弱脂肪细胞的脂解作用,并抑制 TNFα 刺激的 ERK、JNK、IKK 的磷酸化。然而,芍药苷对脂肪细胞胰岛素抵抗和脂肪细胞因子变化的影响尚不清楚。本研究旨在探讨芍药苷在预防 TNFα 处理的 3T3-L1 脂肪细胞胰岛素抵抗和炎症中的作用。我们的结果表明,芍药苷恢复了 TNFα 降低的胰岛素刺激的 [(3)H]2-DOG 摄取,同时恢复了 IRS-1 的丝氨酸磷酸化和脂肪细胞中胰岛素刺激的 AKT 磷酸化。芍药苷减弱了 TNFα 介导的 PPARγ 及其靶基因表达的抑制作用,GW9662(PPARγ 活性的拮抗剂)减弱了芍药苷对 TNFα 诱导的胰岛素抵抗的改善作用。此外,芍药苷可抑制 TNFα 诱导的脂肪细胞中 IL-6 和 MCP-1 的表达和分泌。这些结果与我们之前的数据一起表明,芍药苷对脂肪细胞具有有益的作用,可预防 TNFα 诱导的胰岛素抵抗和炎症性脂肪细胞因子释放。我们的研究为芍药苷改善 TNFα 诱导的脂肪细胞功能障碍的能力提供了重要证据,这有助于阐明其在肥胖治疗中的潜在作用。