Seed region SNPs alter miRNA expression profile in response to insulin in bovine adipose tissue in vivo

胰岛素是一种有效的脂肪生成和体内平衡调节剂。低胰岛素血症和脂肪组织（AT）胰岛素反应性降低同时发生在哺乳期早期，导致乳腺胰岛素非依赖型摄取的葡萄糖可用性增加和AT的更大动员。尽管有一些证据表明在哺乳早期脂肪中与胰岛素信号相关的一些基因发生了变化，但转录后机制仍不清楚。微RNA （miRNA）是四种小的、系统发育上保守的非蛋白质编码RNA之一，通过抑制蛋白质翻译或破坏靶mRNA的稳定来介导转录后基因抑制。在人类中，胰岛素影响微RNA （miRNA）的表达谱。此外，有报道表明miRNAs的单核苷酸多态性（snp）对人类药物反应的个体差异有影响。在本项目中，将使用牛体内模型来研究哺乳早期胰岛素对皮下AT转录后表达谱的影响。此外，我们将利用分子方法鉴定牛AT中差异表达（上调或下调）mirna的种子区snp。为了证实鉴定的miRNA突变对靶基因mRNA降解的差异影响，我们将在体外研究中使用报告载体。这将是第一个暗示miRSNP（微RNA SNP）在泌乳早期牛SC胰岛素反应的研究。

Insulin is a potent regulator of lipogenesis and homeostasis. Hypo-insulinemia and decreased insulin responsiveness of adipose tissue (AT) occur simultaneously in early lactation, resulting in increased glucose availability for insulin-independent uptake by the mammary gland and greater mobilization of AT. Although there is some evidence for changes in some genes associated with insulin signaling in adipose during early lactation, post-transcriptional mechanisms remain unknown. Micro RNA (miRNA) are one of four small, phylogeneticallyconserved, non–protein-coding RNAs that mediate posttranscriptional gene repression by inhibiting protein translation or by destabilizing target mRNA. In humans, insulin affects the micro RNA (miRNA) expression profile. Further, there are reports indicating the effect of miRNAs’ single nucleotide polymorphisms (SNPs) on inter-individual differences in drug response in humans. In this project, a bovine in vivo model will be used to study the effect of insulin in early lactation on post-transcriptional expression profile in subcutaneous (SC) AT. Furthermore, we will identify the seed region SNPs of differentially expressed (up- or downregulated) miRNAs using molecular approaches in bovine AT. To confirm the differential effect of identified miRNA mutations on the target genes’ mRNA degradation, we will use a reporter vector in an in vitro study. This will represent the first study implicating miRSNP (Micro RNA SNP) on insulin response in bovine SC in early lactation.