MicroRNAs in brown fat development and metabolism

MicroRNA 在棕色脂肪发育和代谢中的作用

基本信息

批准号：
8895310
负责人：
Yong-Xu Wang
金额：
$ 36.43万
依托单位：
UNIV OF MASSACHUSETTS MED SCH WORCESTER
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-07-21 至 2018-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8895310
关键词：
3&apos Untranslated Regions Address Adipocytes Adipose tissue Adult Affect Animals Base Pairing Boxing Brown Fat Cell Culture Techniques Cell Differentiation process Cell physiology Cells Characteristics Cyclic GMP Cyclic GMP-Dependent Protein Kinases Cyclic Nucleotides Data Development Developmental Process Diet Down-Regulation Energy Metabolism Exons Fatty acid glycerol esters Gene Expression Genes Goals Human In Vitro Insulin Resistance Introns Lead Mediating Messenger RNA Metabolic Metabolic Diseases Metabolism MicroRNAs Modeling Molecular Mus Nature Non-Insulin-Dependent Diabetes Mellitus Obesity PPAR Pathway Pathway interactions Phenotype Phosphodiesterase Inhibitors Physiological Physiology Play Proteins Regulation Resistance Role Seeds Signal Pathway Signal Transduction Signaling Molecule Site Small RNA Surveys Therapeutic Tissues Transgenes Transgenic Mice Translational Repression Untranslated RNA energy balance improved in vivo inhibitor/antagonist insulin sensitivity interest lipid biosynthesis member overexpression phosphoric diester hydrolase prevent public health relevance research study selective expression therapeutic target transcriptome sequencing

项目摘要

Project Summary/Abstract Our long-range goal is to understand molecular pathways that govern brown fat development and function. In contrast to white fat, brown fat is a tissue that is specialized in energy expenditure. It is present in adult humans and its activity is inversely associated with human obesity. Thus, brown fat is potentially an attractive therapeutic target tissue for obesity and metabolic diseases. We are interested in how brown fat development and function is regulated by miRNAs, a class of small RNAs that do not encode protein yet control many developmental and cellular processes. We have identified a set of miRNAs that are selectively expressed in the brown fat. We found that, one of them, when expressed in the brown fat, remarkably expands the brown fat depots of mice, and as a result, the animals have less white fat mass and are resistant to diet-induced obesity. Our hypothesis is that this miRNA promotes brown fat cell differentiation by activating a cGMP- dependent signaling pathway. In the first aim, we will analyze in detail whether the expanded brown fat depots are true brown fat and are functional. We will determine whether the expanded brown fat improves metabolic parameters and enhances insulin sensitivity. We will determine whether the expanded brown fat prevents genetically predisposed obesity. In the second aim, we will perform cell culture studies to further validate that this miRNA promotes brown cell differentiation. We will examine whether the miRNA represses the expression of a negative regulator in the cGMP-dependent signaling pathway. In the third aim, we will determine whether the miRNA activates the cGMP-dependent signaling pathway. Our studies will likely provide useful information on whether mimics of this miRNA have therapeutic potentials for obesity and metabolic diseases.

项目概要/摘要我们的长期目标是了解控制棕色脂肪发育和功能的分子途径。在与白色脂肪相反，棕色脂肪是一种专门负责能量消耗的组织。它存在于成人中人类及其活动与人类肥胖呈负相关。因此，棕色脂肪具有潜在的吸引力肥胖和代谢疾病的治疗靶组织。我们感兴趣的是棕色脂肪是如何发育的其功能由 miRNA 调节，miRNA 是一类小 RNA，不编码蛋白质，但控制许多功能。发育和细胞过程。我们已经鉴定出一组选择性表达的 miRNA 棕色脂肪。我们发现，其中一种在棕色脂肪中表达时，会显着扩大棕色脂肪小鼠的脂肪库，因此，动物的白色脂肪量较少，并且对饮食诱导的抵抗力肥胖。我们的假设是这种 miRNA 通过激活 cGMP-促进棕色脂肪细胞分化依赖的信号通路。在第一个目标中，我们将详细分析扩大的棕色脂肪库是否是真正的棕色脂肪并且具有功能性。我们将确定扩大的棕色脂肪是否改善新陈代谢参数并增强胰岛素敏感性。我们将确定扩大的棕色脂肪是否可以预防有遗传倾向的肥胖。在第二个目标中，我们将进行细胞培养研究以进一步验证该 miRNA 促进棕色细胞分化。我们将检查 miRNA 是否抑制表达 cGMP 依赖性信号通路中的负调节因子。在第三个目标中，我们将确定是否 miRNA 激活 cGMP 依赖性信号通路。我们的研究可能会提供有用的信息研究该 miRNA 的模拟物是否具有治疗肥胖和代谢疾病的潜力。