Prevalence of obesity becomes an important health issue worldwide, but the management of obesity remains unsatisfied. This study aimed to explore the mechanism of long non-coding RNA TUG/miR-204/SIRT1 axis, which was involved in the pathogenesis of obesity. Obesity mouse model was induced by high-fat diet and treated with taurine upregulated gene1 (TUG1) virus via tail intravenous injection. Then, body weight, serum glucose, insulin tolerance, testicular fat weight were detected, as well as the expression of TUG1, microRNA-204 (miR-204), sirtuin1 (SIRT1), and inflammation and fatty accumulation associated proteins and cytokines. Regulatory relationship between TUG1/SIRT1 and miR-204 was confirmed by dual-luciferase reporter activity assay. A high-glucose-induced 3T3-L1 cell model was also constructed to explore the regulatory mechanism of TUG/miR-204/SIRT1 axis in the pathogenesis of obesity at cell level after altering the expression of TUG1, miR-204, and SIRT1. Overexpression of TUG1 could significantly attenuate the weight, serum glucose, glucose, insulin tolerance, fatty accumulation, and inflammation in obesity mice, as well as the elevation of miR-204, but increase the expression of SIRT1, phosphorylated AKT (p-AKT), glucose transporter4 (GLUT4), and peroxisome proliferator activated receptorγ (PPARγ). Both TUG1 and SIRT1 were targets of miR-204 and could be negatively regulated by miR-204. Overexpression of TUG1 could suppress the inflammation in adipocytes via downregulating miR-204 and promote GLUT4/PPARγ/AKT pathway high-glucose-induced inflammation in 3T3-L1 cells. miR-204 inhibitors could also suppress high-glucose-induced inflammation in 3T3-L1 cells via promoting SIRT1/ GLUT4/PPARγ/AKT pathway. LncRNA TUG1 could negatively regulate miR-204 to alleviate inflammation and insulin tolerance via promoting SIRT1/GLUT4/PPARγ/AKT pathway.

肥胖症的流行已成为世界范围内重要的健康问题，但肥胖症的治疗仍未令人满意。本研究旨在探讨长的非编码RNA TUG / miR-204 / SIRT1轴的机制，该机制与肥胖的发病机制有关。高脂饮食诱导肥胖小鼠模型，并经尾静脉注射牛磺酸上调的gene1（TUG1）病毒治疗。然后，检测体重，血清葡萄糖，胰岛素耐受性，睾丸脂肪重量，以及TUG1，microRNA-204（miR-204），sirtuin1（SIRT1）的表达以及炎症和脂肪堆积相关蛋白和细胞因子的表达。TUG1 / SIRT1和miR-204之间的调节关系已通过双荧光素酶报道分子活性测定得以证实。还构建了高葡萄糖诱导的3T3-L1细胞模型，以在改变TUG1，miR-204和SIRT1的表达后探索TUG / miR-204 / SIRT1轴在肥胖发病机理中的调控机制。TUG1的过度表达可以显着减轻肥胖小鼠的体重，血糖，葡萄糖，胰岛素耐受性，脂肪蓄积和炎症以及miR-204的升高，但会增加SIRT1，磷酸化AKT（p-AKT）的表达。 ，葡萄糖转运蛋白4（GLUT4）和过氧化物酶体增殖物激活受体γ（PPARγ）。TUG1和SIRT1都是miR-204的靶标，并且可能受到miR-204的负调控。TUG1的过表达可以通过下调miR-204抑制脂肪细胞的炎症，并促进GLUT4 /PPARγ/ AKT途径高糖诱导的3T3-L1细胞炎症。miR-204抑制剂还可以通过促进SIRT1 / GLUT4 /PPARγ/ AKT途径来抑制高糖诱导的3T3-L1细胞炎症。LncRNA TUG1可能通过促进SIRT1 / GLUT4 /PPARγ/ AKT途径而负调控miR-204，减轻炎症和胰岛素抵抗。