TRB3 gene silencing activates AMPK in adipose tissue with beneficial metabolic effects in obese and diabetic rats
TRB3 gene silencing activates AMPK in adipose tissue with beneficial metabolic effects in obese and diabetic rats
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TRB3 基因沉默激活脂肪组织中的 AMPK，对肥胖和糖尿病大鼠产生有益的代谢作用
DOI：
10.1016/j.bbrc.2017.04.154
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发表时间：
2017
影响因子：
3.1
通讯作者：
Ti Yun
中科院分区：
文献类型：
--
作者：
Sun Xiaoyan;Song Ming;Wang Hui;Zhou Huimin;Wang Feng;Li Ya;Zhang Yun;Zhang Wei;Zhong Ming;Ti Yun
我们之前的研究表明 Tribbles 同源物 3 (TRB3) 可能通过脂肪组织参与代谢综合征。鉴于之前的研究，我们试图确定 TRB3 是否在脂肪细胞和脂肪组织中发挥重要作用，对肥胖和糖尿病大鼠具有有益的代谢作用。培养完全分化的3T3-L1脂肪细胞以诱导胰岛素抵抗脂肪细胞。 40 只雄性 Sprague-Dawley 大鼠全部喂食高脂肪 (HF) 饮食。采用高脂饮食和小剂量链脲佐菌素（STZ）诱导2型糖尿病大鼠模型。与对照组相比，胰岛素抵抗脂肪细胞中胰岛素受体底物1（IRS-1）、葡萄糖转运蛋白4（GLUT4）和磷酸化AMP激活蛋白激酶（p-AMPK）蛋白水平显着降低，TRB3蛋白水平和甘油三酯水平显着升高，葡萄糖摄取显着降低。 TRB3 沉默减轻了脂肪细胞的胰岛素抵抗。 TRB3基因沉默后，脂肪细胞中IRS-1、GLUT4和p-AMPK的蛋白水平显着增加。 TRB3 基因沉默可降低糖尿病大鼠的血糖，改善胰岛素敏感性和脂肪组织重塑。 TRB3 沉默降低了糖尿病附睾和棕色脂肪组织 (BAT) 中的甘油三酯，同时增加了糖原。一致地，TRB3-siRNA 治疗后，糖尿病附睾脂肪组织和 BAT 中的 p-AMPK 水平增加。 TRB3 沉默增加了肝脏中 Akt 的磷酸化，并改善了肝脏胰岛素抵抗。
Our previous study had suggested Tribbles homolog 3 (TRB3) might be involved in metabolic syndrome via adipose tissue. Given prior studies, we sought to determine whether TRB3 plays a major role in adipocytes and adipose tissue with beneficial metabolic effects in obese and diabetic rats. Fully differentiated 3T3-L1 adipocytes were incubated to induce insulin resistant adipocytes. Forty male Sprague–Dawley rats were all fed high-fat (HF) diet. Type 2 diabetic rat model was induced by high-fat diet and low-dose streptozotocin (STZ). Compared with control group, in insulin resistant adipocytes, protein levels of insulin receptor substrate-1(IRS-1), glucose transporter 4(GLUT4) and phosphorylated-AMP-activated protein kinase (p-AMPK)were reduced, TRB3 protein level and triglyceride level were significantly increased, glucose uptake was markedly decreased. TRB3 silencing alleviated adipocytes insulin resistance. With TRB3 gene silencing, protein levels of IRS-1, GLUT4 and p-AMPK were significantly increased in adipocytes. TRB3 gene silencing decreased blood glucose, ameliorated insulin sensitivity and adipose tissue remodeling in diabetic rats. TRB3 silencing decreased triglyceride, increased glycogen simultaneously in diabetic epididymal and brown adipose tissues (BAT). Consistently, p-AMPK levels were increased in diabetic epididymal adipose tissue, and BAT after TRB3-siRNA treatment. TRB3silencing increased phosphorylation of Akt in liver, and improved liver insulin resistance.