The role of microRNA in body weight maintenance

microRNA在体重维持中的作用

• 批准号: 225913418
• 负责人: Professor Dr. Nikolaus Rajewsky
• 金额: --
• 依托单位: Systembiologie von Gen-regulatorischen Elementen
• 依托单位国家: 德国
• 项目类别: Clinical Research Units
• 财政年份: 2012
• 资助国家: 德国
• 起止时间: 2011-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/225913418?language=en
• 关键词: role; microRNA; body; weight; maintenance

MicroRNAs (miRNAs) are now known as a large class of small non-coding RNAs, which post-transcriptionally regulate the expression of a large fraction of all animal genes. Due to this ability, miRNAs are important in a wide range of biological processes. Notably, miRNAs are known regulators of metabolic processes such as insulin secretion, and have recently been implicated in the regulation of diet-induced obesity in mice. The presence of circulating miRNAs in patient serum has attracted considerable amount of interest (1; 2). This is due to the fact, that –surprisingly- the stability of such serum-miRNAs is rather high and is likely caused by exosomes or other forms of microvesicles, which bind to miRNAs. Another reason for the high interest in circulating serum-miRNAs is the finding that individual miRNAs can correlate with specific disease states (such as HPV-infection, coronary heart disease and others). Yet, in most of these cases little is known, where these miRNAs originate from, or if they are functional. We have sequenced serum-miRNAs of mouse and man and have uncovered an astonishing degree of conservation of miRNA expression levels between these species. The number of known and unknown miRNAs in the different mouse and human sera surpassed the expectation and is larger than in any other available data sets. Importantly, the profiles of the serum-miRNA from lean and obese mice strongly support our hypotheses that miRNA can serve as obesity-related biomarkers. As a next step the clinical relevance of this finding shall be determined by analyzing if such obesity-related serum miRNAs are conserved in mouse and human serum. If conserved individual miRNAs or miRNA patterns are identified it will be possible to predict the prospective targets and the matching signaling pathways. Moreover, we wish to analyze in greater detail, if single miRNAs are associated with long-term outcome of weight maintenance after weight loss in the two patient cohorts of the Z-project. In addition the immense depth of our currently established data, shall also be used cooperatively to establish if miRNAs in the hypothalamus (as a central relais of the leptin-signal), are specifically regulated. Moreover, we will establish animal models to follow our hypotheses of a new endocrine function of serum miRNAs. In particular we will follow the question where the serum miRNAs that are associated with weight regulating parameters originate from, where their targets are and which physiological functions they might have.

MicroRNAs （miRNAs）现在被认为是一类小的非编码rna，它们在转录后调节大部分动物基因的表达。由于这种能力，mirna在广泛的生物过程中很重要。值得注意的是，mirna是已知的代谢过程（如胰岛素分泌）的调节因子，并且最近被认为与小鼠饮食诱导的肥胖调节有关。患者血清中循环mirna的存在引起了相当大的兴趣（1;2）。这是因为，令人惊讶的是，这些血清mirna的稳定性相当高，可能是由外泌体或其他形式的微囊泡结合mirna引起的。对循环血清mirna的高度兴趣的另一个原因是发现单个mirna可以与特定的疾病状态（如hpv感染，冠心病等）相关。然而，在大多数情况下，人们对这些mirna的来源以及它们是否具有功能知之甚少。我们已经对小鼠和人类的血清miRNA进行了测序，并发现了这些物种之间miRNA表达水平的惊人程度的守恒。在不同的小鼠和人类血清中已知和未知的mirna数量超过了预期，并且比任何其他可用的数据集都要大。重要的是，来自瘦和肥胖小鼠的血清miRNA谱强烈支持我们的假设，即miRNA可以作为肥胖相关的生物标志物。下一步，通过分析这些肥胖相关的血清mirna是否在小鼠和人类血清中保存，来确定这一发现的临床相关性。如果确定了保守的单个miRNA或miRNA模式，就有可能预测潜在的靶标和匹配的信号通路。此外，我们希望更详细地分析，在z项目的两个患者队列中，单个mirna是否与减肥后体重维持的长期结果相关。此外，我们目前已建立的数据的巨大深度，还应合作用于确定下丘脑（作为瘦素信号的中心关系）中的mirna是否受到特异性调节。此外，我们将建立动物模型，以遵循我们对血清mirna的新内分泌功能的假设。特别是，我们将遵循与体重调节参数相关的血清mirna的起源，它们的靶点在哪里以及它们可能具有哪些生理功能的问题。