Jiang Xinye, Xue Mei, Fu Ziyi, Ji Chenbo, Guo Xirong, Zhu Lu, Xu Lulian, Pang Lingxia, Xu Meiyu, Qu Hongming
Affiliated Nanjing Maternity and Child Health Hospital, Nanjing Medical University, Nanjing, China.
Cell Physiol Biochem. 2014;33(6):1778-88. doi: 10.1159/000362957. Epub 2014 May 27.
BACKGROUND/AIMS: Obesity and the related metabolic syndrome have emerged as major public health issues in modern society. miRNAs have been shown to play key roles in regulating obesity-related metabolic syndrome, and some miRNAs regulated by adiponectin were identified as novel targets for controlling adipose tissue inflammation. miR-378 is a candidate target that was shown to be involved in adipose differentiation, mitochondrial metabolism and systemic energy homeostasis. However, little is known about the regulatory mechanisms of miR-378 expression. To better understand the physiological role of miR-378 in obesity and metabolic syndrome, it is crucial that we understand the regulation of miR-378 gene expression in human adipocytes.
In this study, we investigated the effects of adipokines and inflammatory cytokines on miR-378 expression using Real-time PCR and the potential regulatory mechanisms using luciferase reporter assays and electrophoretic mobility shift assay (EMSA). Results : We found that adipokines and cytokines upregulated miR-378 expression primarily through SREBP and C/EBP binding sites in the miR-378 promoter region.
Our findings showed that adipokines induced miR-378 expression and revealed the most likely mechanism of adipokine-induced miR-378 dysregulation in human adipocytes. miRNAs have been shown to function in regulating obesity-related metabolic syndrome, and miR-378 may be a novel target for controlling adipose tissue inflammation. This study offers a theoretical basis for understanding systemic adipose tissue inflammation and may provide new strategies for clinical treatment.
背景/目的：肥胖及相关代谢综合征已成为现代社会的主要公共卫生问题。微小RNA（miRNA）已被证明在调节肥胖相关代谢综合征中起关键作用，一些受脂联素调节的miRNA被确定为控制脂肪组织炎症的新靶点。miR-378是一个候选靶点，已被证明参与脂肪分化、线粒体代谢和全身能量稳态。然而，关于miR-378表达的调控机制知之甚少。为了更好地理解miR-378在肥胖和代谢综合征中的生理作用，了解其在人类脂肪细胞中的基因表达调控至关重要。
在本研究中，我们使用实时定量聚合酶链反应（Real-time PCR）研究了脂肪因子和炎性细胞因子对miR-378表达的影响，并使用荧光素酶报告基因检测和电泳迁移率变动分析（EMSA）研究了潜在的调控机制。结果：我们发现脂肪因子和细胞因子主要通过miR-378启动子区域的固醇调节元件结合蛋白（SREBP）和CCAAT/增强子结合蛋白（C/EBP）结合位点上调miR-378的表达。
我们的研究结果表明脂肪因子诱导miR-378表达，并揭示了人类脂肪细胞中脂肪因子诱导miR-378失调的最可能机制。miRNA已被证明在调节肥胖相关代谢综合征中发挥作用，miR-378可能是控制脂肪组织炎症的新靶点。本研究为理解全身脂肪组织炎症提供了理论基础，并可能为临床治疗提供新策略。
