MiRNA-181a regulates adipogenesis by targeting tumor necrosis factor-α (TNF-α) in the porcine model.
MiRNA-181a regulates adipogenesis by targeting tumor necrosis factor-α (TNF-α) in the porcine model.
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DOI：
10.1371/journal.pone.0071568
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Li H;Chen X;Guan L;Qi Q;Shu G;Jiang Q;Yuan L;Xi Q;Zhang Y
脂肪生成通过改变基因表达而受到严格调控，并且TNF-α是在调节脂肪生成中起重要作用的多功能细胞因子。microRNA是细胞分化的强转录后调节因子。在我们之前的工作中，我们发现miR-181 a在脂肪丰富的猪品种中高表达。利用生物信息学分析，miR-181 a被鉴定为TNF-α的潜在调节剂。在这里，我们通过双荧光素酶测定验证了TNF-α作为miR-181 a的靶点。为了响应脂肪形成，使用模拟物或抑制剂来过表达或减少猪前脂肪细胞中的miR-181 a表达，然后将其诱导成成熟脂肪细胞。过表达miR-181 a可加速脂滴的积聚，增加甘油三酯的量，并抑制TNF-α蛋白的表达，而抑制剂则具有相反的作用。同时，TNF-α通过miR 181 a模拟物挽救了增加的脂肪生成。此外，miR-181 a抑制降低了脂肪合成相关基因PDE 3B（磷酸二酯酶3B）、LPL（脂蛋白脂肪酶）、PPARγ（增殖物激活受体-γ）、GLUT 1（葡萄糖转运蛋白）、GLUT 4、脂联素和FIGH（脂肪酸合成酶）以及关键脂解基因HSL（脂肪敏感性脂肪酶）和ATGL（脂肪甘油三酯脂肪酶）的表达，如定量实时PCR所示。本研究首次证实了miR-181 a通过调节TNF-α在脂肪细胞分化中的作用，可能成为抗肥胖药物的新靶点。
Adipogenesis is tightly regulated by altering gene expression, and TNF-α 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-α. Here, we validated TNF-α 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-α 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), PPARγ (proliferator-activated receptor-γ), 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-α, which may became a new therapeutic target for anti-obesity drugs.
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影响因子：
14.9
作者：
Chen C;Ridzon DA;Broomer AJ;Zhou Z;Lee DH;Nguyen JT;Barbisin M;Xu NL;Mahuvakar VR;Andersen MR;Lao KQ;Livak KJ;Guegler KJ
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3.7
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通讯作者：
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作者：
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