Background Hepatic insulin resistance (IR) plays a crucial role in the development of many metabolic diseases, such as type 2 diabetes. MicroRNAs (miRNAs) are involved in the pathogenesis of IR and related diseases; however, studies of miRNAs in hepatic IR are limited. Method In this study, we adopted a high-throughput sequencing approach to construct small RNA libraries in the livers of normal mice and high-fat diet-induced hepatic IR mice. Results Through analysis of data, 107 known and 56 novel miRNAs were identified as differentially expressed miRNAs between the two groups. Additionally, bioinformatics methods were used to predict targets of the differentially expressed miRNAs and to explore the potential downstream Gene Ontology categories and Kyoto Encyclopedia of Genes and Genomes pathways. Meanwhile, some differentially expressed miRNAs (miR-34a-5p, miR-149-5p, miR-335-3p, miR-10b-5p, miR-1a-3p, miR-411-5p, and miR-592-5p) were validated by quantitative-time PCR, and their potential target genes related to IR or glycolipid metabolism were also predicted and presented in this study. Conclusion Taken together, our results defined miRNA expression signature that may lead to hepatic IR in mice, and the findings provided a foundation for future studies to further explore the effects and underlying mechanisms of the miRNAs and their target genes in the pathogenesis of hepatic IR and related diseases.

中文翻译：

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小 RNA 的高通量测序和与高脂饮食诱导的小鼠肝脏胰岛素抵抗相关的差异表达 microRNA 的分析。

背景 肝脏胰岛素抵抗 (IR) 在许多代谢疾病的发展中起着至关重要的作用，例如 2 型糖尿病。MicroRNAs (miRNAs) 参与 IR 及相关疾病的发病机制；然而，对肝脏 IR 中 miRNA 的研究是有限的。方法在本研究中，我们采用高通量测序方法在正常小鼠和高脂饮食诱导的肝IR小鼠肝脏中构建小RNA文库。结果通过数据分析，107个已知miRNA和56个新miRNA被鉴定为两组间差异表达的miRNA。此外，生物信息学方法用于预测差异表达的 miRNA 的目标，并探索潜在的下游基因本体类别和京都基因百科全书和基因组途径。同时，验证了一些差异表达的 miRNA（miR-34a-5p、miR-149-5p、miR-335-3p、miR-10b-5p、miR-1a-3p、miR-411-5p 和 miR-592-5p）通过定量时间PCR，本研究还预测并提出了它们与IR或糖脂代谢相关的潜在靶基因。综上所述，我们的研究结果确定了可能导致小鼠肝脏 IR 的 miRNA 表达特征，为进一步探索 miRNA 及其靶基因在肝脏 IR 发病机制中的作用和潜在机制提供了基础。相关疾病。