MiR-455 targeting SOCS3 improve liver lipid disorders in diabetic mice
MiR-455 targeting SOCS3 improve liver lipid disorders in diabetic mice
复制标题
MiR-455 靶向 SOCS3 可改善糖尿病小鼠的肝脏脂质紊乱
DOI：
10.1080/21623945.2020.1749495
复制
发表时间：
2020-01-01
期刊：
影响因子：
3.3
通讯作者：
Guan, Meiping
中科院分区：
文献类型：
--
作者：
Fang, Shu;Feng, Jie;Guan, Meiping
miR-455 已被证实是棕色脂肪组织的关键调节因子，并且脂肪组织特异性过度表达 miR-455 (ap2-miR-455) 小鼠可以对抗高脂肪饮食引起的肥胖。本研究旨在验证miR-455的过度表达可以改善db/db糖尿病小鼠肝脏中的脂质积累和代谢，并探讨其潜在机制。糖尿病小鼠（db/db）和对照小鼠（db/m）被随机分为四组。 db/db小鼠肝脏过表达miR-455后，血清和肝脏中甘油三酯水平均下降，肝脏脂质沉积改善，脂肪酸合成酶、硬脂酰辅酶A去饱和酶1、甾醇调节元件结合蛋白1c（SREBP-1c）和乙酰辅酶A羧化酶（ACCα）的表达也显着下调。 TargetScan表明细胞因子信号传导抑制因子3（SOCS3）以miR-455为靶标，干预后db/db小鼠肝脏中SOCS3的蛋白显着降低。双荧光素酶报告基因检测显示SOCS3是miR-455的靶基因。体外，在棕榈酸（PA）刺激的人正常肝（LO2）细胞中，转染的miR-455模拟物可以显着抑制SOCS3的表达，而转染的miR-455抑制剂可以上调SOCS3的表达。 SOCS3的siRNA转染LO2细胞可显着下调SREBP-1c和ACC α的蛋白表达。我们的研究表明，肝脏中miR-455的过度表达可以通过下调其靶基因SOCS3来改善糖尿病小鼠的脂质代谢。
MiR-455 has been verified a key regulator of brown adipose tissue and adipose tissue-specific overexpression of miR-455 (ap2-miR-455) mice could combat high-fat-diet-induced obesity. This study is to verify overexpression of miR-455 could ameliorate the lipid accumulation and metabolism in the liver of db/db diabetic mice and explore the potential mechanisms. Diabetic mice (db/db) and control mice (db/m) were randomly divided into four groups. After overexpression of miR-455 in the liver of db/db mice, the triglycerides level in both serum and liver decreased, the lipid deposit in liver was improved, the expression of fatty acid synthase, stearoyl-CoA desaturase 1, sterol regulatory element binding protein 1c (SREBP-1c) and acetyl-CoA carboxylase (ACC alpha) was also significantly down-regulated. TargetScan indicated that suppressor of cytokine signalling 3 (SOCS3) is predicated to target miR-455 and the protein of SOCS3 in the liver of db/db mice after intervention was significantly decreased. The dual luciferase reporter assay showed that SOCS3 was target gene of miR-455. In vitro, in Palmitate (PA)-stimulated human normal liver (LO2) cells, transfected miR-455 mimic could significantly inhibit the expression of SOCS3, while transfected miR-455 inhibitor could up-regulate the expression of SOCS3. Transfecting LO2 cells with siRNA of SOCS3 could significantly down-regulate the protein expression of SREBP-1c and ACC alpha. Our study showed that overexpression of miR-455 in the liver could improve lipid metabolism in diabetic mice by down-regulating its target gene SOCS3.