PAQR3 regulates phosphorylation of FoxO1 in insulin-resistant HepG2 cells via NF-κB signaling pathway
PAQR3 regulates phosphorylation of FoxO1 in insulin-resistant HepG2 cells via NF-κB signaling pathway
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PAQR3 通过 NF-κB 信号通路调节胰岛素抵抗 HepG2 细胞中 FoxO1 的磷酸化
DOI：
10.1016/j.yexcr.2019.04.031
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发表时间：
2019-08-15
影响因子：
3.7
通讯作者：
Huang, Heqing
中科院分区：
文献类型：
--
作者：
Chen, Lihao;Sun, Xiaohong;Huang, Heqing
胰岛素抵抗是2型糖尿病和糖脂代谢紊乱的一个显着特征。 NF-κB信号通路的激活在胰岛素抵抗的形成中发挥重要作用。 FoxOl在调节葡萄糖和脂质代谢以及胰岛素信号通路中发挥重要作用。既往研究表明孕激素和AdipoQ受体3(PAQR3)抑制FoxOl上游通路PI3K/Akt的活性，并通过激活NF-κB通路促进糖尿病肾炎性纤维化的病理过程。在此基础上，NF-κB是否参与胰岛素抵抗下FoxOl的PAQR3调节引起了我们的极大关注。在本研究中，我们旨在探讨PAQR3是否通过NF-κB通路在棕榈酸（PA）诱导的胰岛素抵抗HepG2细胞中调节FoxO1的磷酸化，从而引起糖脂代谢紊乱。我们发现PA刺激和PAQR3过表达降低了FoxO1的磷酸化以及葡萄糖激酶（GCK）和低密度脂蛋白受体（LDLR）的表达，此外，促进了NF-κB途径的核积累。抑制NF-κB途径增加了FoxO1的磷酸化以及GCK和LDLR的表达，而PA刺激和PAQR3过表达则下调了GCK和LDLR的表达。综上所述，在PA诱导的胰岛素抵抗HepG2细胞中，PAQR3可能通过NF-κB通路调节FoxO1的磷酸化以及GCK和LDLR的表达，从而调节胰岛素抵抗引起的糖脂代谢紊乱。
Insulin resistance is a significant feature of type 2 diabetes mellitus and glucose and lipid metabolism disorders. Activation of NF-kappa B signaling pathway plays an important role in the formation of insulin resistance. FoxOl plays a major role in regulating glucose and lipid metabolism, as well as insulin signaling pathway. Previous studies have shown that Progestin and AdipoQ Receptor 3 (PAQR3) suppresses the activity of PI3K/Akt, which is an upstream pathway of FoxOl, and additionally promotes the pathological process of diabetic renal inflammatory fibrosis via activating NF-kappa B pathway. On this basis, it has caused us great concern whether NF-kappa B is involved in PAQR3 regulation of FoxOl under insulin resistance. In this study, we aimed to investigate whether PAQR3 regulates phosphorylation of FoxO1 via NF-kappa B pathway in palmitic acid (PA)-induced insulin-resistant HepG2 cells, thereby causing glucose and lipid metabolism disorders. We found that PA stimulation and PAQR3 overexpression decreased the phosphorylation of FoxOl and the expressions of glucokinase (GCK) and low density lipoprotein receptor (LDLR), in addition, promoted the nuclear accumulation of NF-kappa B. Inhibit ion of NF-kappa B pathway increased the phosphorylation of FoxO1 and the expressions of GCK and LDLR which were down regulated by PA stimulation and PAQR3 overexpression. Taken together, in PA-induced insulin-resistant HepG2 cells, PAQR3 might regulate the phosphorylation of FoxO1 and the expressions of GCK and LDLR through NF-kappa B pathway, thereby regulating the glucose and lipid metabolism disorders induced by insulin resistance.