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 (ACCα) 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 ACCα. 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.

中文翻译：

---

靶向SOCS3的MiR-455可改善糖尿病小鼠的肝脂质异常。

已经证实，MiR-455是棕色脂肪组织的关键调节剂，miR-455（ap2-miR-455）小鼠的脂肪组织特异性过度表达可以对抗高脂饮食诱导的肥胖症。这项研究是为了验证miR-455的过表达可以改善db / db糖尿病小鼠肝脏中脂质的积累和代谢，并探讨其潜在机制。将糖尿病小鼠（db / db）和对照小鼠（db / m）随机分为四组。db / db小鼠肝脏中miR-455过表达后，血清和肝脏中的甘油三酸酯水平降低，肝脏中的脂质沉积得到改善，脂肪酸合酶，硬脂酰CoA去饱和酶1的表达，固醇调节元件结合蛋白1c（SREBP-1c）和乙酰辅酶A羧化酶（ACCα）也明显下调。TargetScan指出，细胞因子信号传导抑制因子3（SOCS3）的靶标是miR-455，干预后db / db小鼠肝脏中SOCS3的蛋白明显降低。双重荧光素酶报告基因测定表明SOCS3是miR-455的靶基因。在体外，在棕榈酸酯（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。用SOCS3的siRNA转染LO2细胞可以显着下调SREBP-1c和ACCα的蛋白表达。我们的研究表明，miR-455在肝脏中的过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。