Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon 443-721, Republic of Korea.
Metabolism. 2011 Dec;60(12):1781-9. doi: 10.1016/j.metabol.2011.05.003. Epub 2011 Jun 12.
Free fatty acids (FFAs) lead to the activation of inflammatory pathways related to the induction of insulin resistance. Visfatin is known to play a role in obesity-related metabolic diseases and inflammatory conditions. Here, the role of visfatin in FFA-induced inflammation was investigated in hepatocytes. The following factors were examined: (1) the protein and messenger RNA (mRNA) expression of visfatin in the liver tissue of insulin-resistant rats and in (2) in HepG2 cells treated with palmitate, (3) the palmitate-induced mRNA expression and protein synthesis of interleukin-6 and tumor necrosis factor-α in HepG2 cells transfected with visfatin-specific small interfering RNA, and (4) the expression of visfatin in HepG2 cells treated with a nuclear factor-κB (NF-κB) inhibitor (SN50) and infected with Ad-IκBα. The protein and mRNA levels of visfatin were significantly higher in insulin-resistant rat liver tissue compared with the control group. Visfatin expression and protein synthesis significantly increased in HepG2 cells treated with palmitate in a time- and concentration-dependent manner. Visfatin-specific small interfering RNA significantly decreased the palmitate-induced mRNA expression and protein synthesis of interleukin-6 and tumor necrosis factor-α. A NF-κB inhibitor induced the downregulation of visfatin in HepG2 cells following treatment with palmitate. HepG2 cells infected with Ad-IκBα showed decreased expression of visfatin following treatment with palmitate. The expression of visfatin is closely associated with the expression of proinflammatory cytokines in FFA-induced inflammation and is significantly decreased by NF-κB inhibition in HepG2 cells. Visfatin may play a role in FFA-induced inflammation in hepatocytes through the NF-κB pathway.
游离脂肪酸（FFAs）导致与胰岛素抵抗诱导相关的炎症途径的激活。内脏脂肪素已知在肥胖相关代谢性疾病和炎症状态中发挥作用。在这里，研究了内脏脂肪素在 FFAs 诱导的肝细胞炎症中的作用。检查了以下因素：（1）胰岛素抵抗大鼠肝组织中内脏脂肪素的蛋白质和信使 RNA（mRNA）表达，以及（2）棕榈酸处理的 HepG2 细胞中，（3）用内脏脂肪素特异性小干扰 RNA 转染的 HepG2 细胞中转录的白细胞介素-6 和肿瘤坏死因子-α的 mRNA 表达和蛋白合成，以及（4）用核因子-κB（NF-κB）抑制剂（SN50）处理的 HepG2 细胞中的内脏脂肪素表达和感染 Ad-IκBα。与对照组相比，胰岛素抵抗大鼠肝组织中的内脏脂肪素蛋白和 mRNA 水平明显更高。棕榈酸处理的 HepG2 细胞中，内脏脂肪素表达和蛋白合成呈时间和浓度依赖性增加。内脏脂肪素特异性小干扰 RNA 显著降低了棕榈酸诱导的白细胞介素-6 和肿瘤坏死因子-α的 mRNA 表达和蛋白合成。NF-κB 抑制剂在棕榈酸处理后诱导 HepG2 细胞中内脏脂肪素的下调。用棕榈酸处理后，感染 Ad-IκBα 的 HepG2 细胞中内脏脂肪素的表达减少。在 FFAs 诱导的炎症中，内脏脂肪素的表达与促炎细胞因子的表达密切相关，在 HepG2 细胞中 NF-κB 抑制可显著降低其表达。内脏脂肪素可能通过 NF-κB 途径在 FFAs 诱导的肝细胞炎症中发挥作用。
