miR-129-5p Inhibits Adipogenesis through Autophagy and May Be a Potential Biomarker for Obesity
miR-129-5p Inhibits Adipogenesis through Autophagy and May Be a Potential Biomarker for Obesity
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miR-129-5p 通过自噬抑制脂肪生成，可能是肥胖的潜在生物标志物
DOI：
10.1155/2019/5069578
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发表时间：
2019-11-06
影响因子：
2.8
通讯作者：
Zhang, Zhiguo
中科院分区：
文献类型：
--
作者：
Fu, Xue;Jin, Lina;Zhang, Zhiguo
前言肥胖的发病机制尚不清楚。microRNAs（miRNAs）可能通过调节脂肪细胞分化而发挥生物活性分子的作用。本研究旨在鉴定miR-129- 5 p（一种特异性miRNA）如何在体外调控脂肪生成，并探讨其在人类肥胖发病机制中的可能作用。材料与方法检测肥胖小鼠模型中miR-129- 5 p的表达。观察miR-129- 5 p对脂肪细胞分化的影响，并分析脂肪标志物。应用生物信息学和双荧光素酶报告基因分析技术预测并确认miR-129- 5 p的靶基因。对人血清样品进行检测和分析。结果miR-129- 5 p在db/db小鼠脂肪组织中高表达。功能获得和功能丧失研究表明，miR-129- 5 p在体外可显著抑制脂肪细胞分化和白色脂肪细胞布朗宁，并降低成熟白色和棕色脂肪细胞中特异性标志物如FABP 4、UCP 1和PPARγ的水平。miR-129- 5 p直接靶向ATG 7，这是生物信息学预测的，并通过双荧光素酶报告基因测定证实。单纯性肥胖患者血清miR-129- 5 p水平明显升高（p < 0.01），并与BMI（r = 0.407，p < 0.029）、体脂百分比（r = 0.394，p < 0.038）等肥胖指标相关。结论miR-129- 5 p可能靶向调控白色和棕色脂肪形成的ATG 7相关自噬信号网络。重要的是，上述结果表明血清miR-129- 5 p可能是肥胖的潜在生物标志物和治疗靶点。
Introduction Obesity has an unclear pathogenesis. MicroRNAs (miRNAs) may function as biologically active molecules for obesity through regulating adipocyte differentiation. This study aimed to identify how miR-129-5p (a specific miRNA) regulates adipogenesis in vitro and explore its possible role in the pathogenesis of obesity in humans. Materials and Methods The miR-129-5p expression was detected in obese mouse models. The effect of miR-129-5p on adipocyte differentiation was observed, and the adipose markers were analyzed. Bioinformatics and dual-luciferase reporter assay were applied to predict and confirm the target genes of miR-129-5p. The human serum samples were detected and analyzed. Results miR-129-5p is highly expressed in adipose tissues of db/db mice. Gain- and loss-of-function studies show that miR-129-5p could significantly inhibit adipocyte differentiation and white adipocyte browning in vitro and decreases the level of specific markers, such as FABP4, UCP1, and PPARγ, in mature white and brown adipocytes. miR-129-5p directly targets ATG7 which is predicted with bioinformatics and confirmed by dual-luciferase reporter assay. Serum miR-129-5p level was evidently elevated in patients with simple obesity (p < 0.01) and correlates with obesity indices, including BMI (r = 0.407, p < 0.029) and fat percentage (r = 0.394, p < 0.038). Conclusion miR-129-5p might target on the ATG7-related autophagy signaling network that regulates white and brown adipogenesis. Importantly, the aforementioned results suggest serum miR-129-5p might be a potential biomarker and therapeutic target for obesity.