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miR-125b通过靶向硬脂酰辅酶A去饱和酶-1(SCD-1)在脂肪生成中起关键作用。

Critical role of miR-125b in lipogenesis by targeting stearoyl-CoA desaturase-1 (SCD-1).

作者信息

Cheng X, Xi Q-Y, Wei S, Wu D, Ye R-S, Chen T, Qi Q-E, Jiang Q-Y, Wang S-B, Wang L-N, Zhu X-T, Zhang Y-L

出版信息

J Anim Sci. 2016 Jan;94(1):65-76. doi: 10.2527/jas.2015-9456.

Abstract

Alteration of gene expression tightly regulates lipogenesis. Stearoyl-CoA desaturase-1 (SCD-1), a key enzyme in lipogenesis, catalyzes the conversion of SFA to MUFA, and inhibition of its activity impairs lipid synthesis. As posttranscriptional regulators, microRNAs are involved in many pathways of lipid metabolism; however, their effect on SCD-1 has not been reported. In this study, miR-125b was identified as a potential regulator of SCD-1 using bioinformatics analysis. Here, we validated SCD-1 as the target of miR-125b using a dual luciferase assay. During adipogenesis, a synthetic mimic or inhibitor was used to overexpress or reduce the expression of miR-125b in porcine adipocytes. Overexpression of miR-125b reduced the accumulation of lipid droplets and triglycerides concentration and repressed SCD-1 protein expression and MUFA composition. The inhibitor had the reverse effect. Small interfering RNA against tested in adipocytes further proved the direct correlation between miR-125b and SCD-1. Moreover, in vivo experiments in mice showed that injection of miR-125b expression vector decreased the hepatic triglycerides concentration relative to saline. This study indicated that miR-125b regulates lipogenesis by targeting SCD-1; therefore, miR-125b might be applied in therapy of lipid metabolism disorders.

摘要

基因表达的改变严格调控脂肪生成。硬脂酰辅酶A去饱和酶-1(SCD-1)是脂肪生成中的关键酶,催化饱和脂肪酸(SFA)向单不饱和脂肪酸(MUFA)的转化,抑制其活性会损害脂质合成。作为转录后调节因子,微小RNA参与脂质代谢的许多途径;然而,它们对SCD-1的影响尚未见报道。在本研究中,通过生物信息学分析鉴定出miR-125b是SCD-1的潜在调节因子。在此,我们使用双荧光素酶测定法验证了SCD-1是miR-125b的靶标。在脂肪生成过程中,使用合成模拟物或抑制剂在猪脂肪细胞中过表达或降低miR-125b的表达。miR-125b的过表达减少了脂滴的积累和甘油三酯浓度,并抑制了SCD-1蛋白表达和MUFA组成。抑制剂则产生相反的效果。在脂肪细胞中针对其进行测试的小干扰RNA进一步证明了miR-125b与SCD-1之间的直接相关性。此外,在小鼠体内实验表明,注射miR-125b表达载体相对于生理盐水降低了肝脏甘油三酯浓度。本研究表明,miR-125b通过靶向SCD-1调节脂肪生成;因此,miR-125b可能应用于脂质代谢紊乱的治疗。

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