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

项目摘要/摘要 我们的长期目标是了解能量动态平衡背后的信号转导途径以及如何 它们的改变会导致肥胖和代谢性疾病。棕色脂肪和棕色样脂肪专门用于 能源支出。它们存在于成年人类中，它们的活动与人类呈负相关 肥胖。因此，棕色脂肪和棕色样脂肪是肥胖和代谢的潜在治疗靶点。 疾病。我们对发现控制白色脂肪“褐变”的新型脂肪因子很感兴趣。我们确定了一个 以前没有特征的分泌性蛋白质，专门在棕色脂肪和棕色脂肪中表达。我们的 初步数据显示，这种脂肪因子在棕色脂肪选择性基因表达和能量中起着关键作用。 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，是白色脂肪褐变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和生热基因表达中的作用 其潜在的机制。在第二个目标中，我们将进行功能增益研究，以分析 这种脂肪因子在体内的代谢表型。在第三个目标中，我们将分析其代谢表型。 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治疗方法 这种脂肪因子在代谢性疾病中的潜力。

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.