MiRNA-181a Regulates Adipogenesis by Targeting Tumor Necrosis Factor-alpha (TNF-alpha) in the Porcine Model

文献类型： 外文期刊

第一作者： Li, Hongyi

作者： Li, Hongyi;Chen, Xiao;Guan, Lizeng;Qi, Qien;Shu, Gang;Jiang, Qingyan;Yuan, Li;Xi, Qianyun;Zhang, Yongliang;Li, Hongyi;Yuan, Li

作者机构：

期刊名称：PLOS ONE （ 影响因子：3.24； 五年影响因子：3.788 ）

ISSN： 1932-6203

年卷期： 2013 年 8 卷 10 期

页码：

收录情况： SCI

摘要： Adipogenesis is tightly regulated by altering gene expression, and TNF-alpha is a multifunctional cytokine that plays an important role in regulating lipogenesis. MicroRNAs are strong post-transcriptional regulators of cell differentiation. In our previous work, we found high expression of miR-181a in a fat-rich pig breed. Using bioinformatic analysis, miR-181a was identified as a potential regulator of TNF-alpha. Here, we validated TNF-alpha as the target of miR-181a by a dual luciferase assay. In response to adipogenesis, a mimic or inhibitor was used to overexpress or reduce miR-181a expression in porcine pre-adipocytes, which were then induced into mature adipocytes. Overexpression of miR-181a accelerated accumulation of lipid droplets, increased the amount of triglycerides, and repressed TNF-alpha protein expression, while the inhibitor had the opposite effect. At the same time, TNF-alpha rescued the increased lipogenesis by miR181a mimics. Additionally, miR-181a suppression decreased the expression of fatty synthesis associated genes PDE3B (phosphodiesterase 3B), LPL (lipoprotein lipase), PPAR gamma (proliferator-activated receptor-gamma), GLUT1(glucose transporter), GLUT4, adiponectin and FASN (fatty acid synthase), as well as key lipolytic genes HSL (hormone-sensitive lipase) and ATGL (adipose triglyceride lipase) as revealed by quantitative real-time PCR. Our study provides the first evidence of the role of miR-181a in adipocyte differentiation by regulation of TNF-alpha, which may became a new therapeutic target for anti-obesity drugs.

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