Regulation of white fat browning by a novel, brown fat-secreted adipokine

新型棕色脂肪分泌脂肪因子对白色脂肪褐变的调节

基本信息

批准号：
9751849
负责人：
Yong-Xu Wang
金额：
$ 41.88万
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：
2018
资助国家：
美国
起止时间：
2018-08-01 至 2021-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9751849
关键词：
Acute Address Adenoviruses Adipocytes Adipose tissue Adrenergic Receptor Adult Age Agonist Binding Biogenesis Body Weight Changes Body mass index Brown Fat Cardiovascular system Catecholamines Cell surface Clinical Cyclic AMP-Dependent Protein Kinases Data Development Ectopic Expression Endocrine Energy Metabolism Expenditure Fatty Liver Fatty acid glycerol esters Gene Expression Genes Genetic Predisposition to Disease Goals Hepatic High Fat Diet Homeostasis Human Human body In Vitro Infection Injections Knock-out Knockout Mice Mediating Metabolic Metabolic Diseases Mitochondria Mus Nerve Obese Mice Obesity Pathway interactions Phenotype Phosphorylation Play Prevention Proteins Recombinant Proteins Recombinants Regulation Resistance Role Serum Proteins Signal Pathway Signal Transduction Signal Transduction Pathway Surface Tail Therapeutic Tissues Transgenic Mice Transgenic Organisms Vascularization Virus adipokines base blood glucose regulation energy balance extracellular functional gain gain of function glucose tolerance improved in vivo insulin sensitivity interest intravenous drip macrophage metabolic phenotype mouse model nerve supply novel novel therapeutics obesity treatment paracrine prevent programs receptor subcutaneous therapeutic target transcriptome sequencing

项目摘要

Project Summary/Abstract Our long-range goal is to understand signal transduction pathways underlying energy homeostasis and how their alterations contribute to obesity and metabolic diseases. Brown fat and brown-like fat are specialized in energy expenditure. They are present in adult humans and their activity is inversely associated with human obesity. Thus, brown fat and brown-like fat represent potential therapeutic target for obesity and metabolic diseases. We are interested in discovering novel adipokines controlling `browning' of white fat. We identified a previously uncharacterized, secreted protein that is specifically expressed in brown fat and brown-like fat. Our preliminary data showed that this adipokine plays a key part in brown fat-selective gene expression and energy expenditure. We hypothesized that this adipokine, through paracrine and endocrine actions, controls thermogenic gene program, and is both necessary and sufficient for white fat browning. In the first aim, we will investigate in detail the roles of this adipokine in thermogenic gene expression in primary adipocyte culture and its underlying mechanism. In the second aim, we will perform gain-of-functional studies to analyze the metabolic phenotype of this adipokine in vivo. In the third aim, we will analyze the metabolic phenotype of mice with adipose tissue-specific deletion of this adipokine gene. Our study will likely reveal the therapeutic potential of this adipokine in metabolic diseases.

项目概要/摘要我们的长期目标是了解能量稳态的信号转导途径以及如何它们的改变会导致肥胖和代谢疾病。棕色脂肪和类棕色脂肪专门用于能量消耗。它们存在于成年人体内，其活动与人类的活动呈负相关。肥胖。因此，棕色脂肪和类棕色脂肪代表了肥胖和代谢的潜在治疗靶点疾病。我们有兴趣发现控制白色脂肪“褐变”的新型脂肪因子。我们确定了一个以前未表征的分泌蛋白，专门在棕色脂肪和类棕色脂肪中表达。我们的初步数据表明，这种脂肪因子在棕色脂肪选择性基因表达和能量方面发挥着关键作用支出。我们假设这种脂肪因子通过旁分泌和内分泌作用控制产热基因程序，对于白色脂肪褐变来说是必要且充分的。在第一个目标中，我们将详细研究该脂肪因子在原代脂肪细胞培养物中产热基因表达中的作用，并其根本机制。在第二个目标中，我们将进行功能获得研究来分析这种脂肪因子在体内的代谢表型。在第三个目标中，我们将分析代谢表型脂肪组织特异性删除该脂肪因子基因的小鼠。我们的研究可能会揭示治疗方法这种脂肪因子在代谢疾病中的潜力。