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

项目总结/摘要 我们的长期目标是了解能量稳态下的信号转导途径，以及如何 它们的改变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中，并且它们的活性与人的免疫力呈负相关。 肥胖因此，棕色脂肪和类棕色脂肪是肥胖和代谢性疾病的潜在治疗靶点。 疾病我们对发现控制白色脂肪“布朗宁”的新脂肪因子感兴趣。我们确定了一个 以前未表征的分泌蛋白，其在棕色脂肪和棕色样脂肪中特异性表达。我们 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中起关键作用。 支出我们假设这种脂肪因子通过旁分泌和内分泌作用， 产热基因程序，是白色脂肪布朗宁的必要条件和充分条件。在第一个目标中，我们将 详细研究这种脂肪因子在原代脂肪细胞培养中产热基因表达中的作用， 其潜在机制。在第二个目标中，我们将进行功能获得研究，以分析 代谢表型的这种脂肪因子在体内。在第三个目标中，我们将分析代谢表型， 具有脂肪组织特异性缺失该脂肪因子基因的小鼠。我们的研究可能会揭示 这种脂肪因子在代谢疾病中的潜力。

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.