An Obesity-Induced Kinase that Regulates Adipose Homeostasis and Metabolic Diseases

项目摘要/摘要 肥胖和2型糖尿病(T2 DM)已成为全国性和全球性的流行病。正在崛起的 肥胖症的流行大大增加了血脂异常、特定类型的癌症、 非酒精性脂肪性肝病、2型糖尿病和心血管疾病是 国家。最近的研究强调了代谢性疾病和脂肪组织之间的密切联系。 发炎。脂肪炎症在代谢综合征的发生发展中起着不可或缺的作用。 脂肪-免疫相互作用对脂肪组织稳态既有积极的影响，也有消极的影响 和全身新陈代谢。是什么引发了脂肪细胞功能障碍和炎症过程 肥胖仍然是一个谜。这项研究计划试图了解 脂肪细胞功能障碍和脂肪炎症是其基础。我们将Fam20c确定为一种新的调节因子 脂肪组织炎症和胰岛素抵抗。肥胖诱导脂肪细胞表达FAM20c。 相反，去除脂肪细胞中的Fam20c可以改善高血糖。在这项建议中，我们寻求 评估胰岛素抵抗和炎症之间的机制联系。我们将致力于以下工作 具体目的：1.确定FAM20C调节能量平衡的生理和细胞机制； 葡萄糖稳态与脂肪组织炎症。2.深入剖析银杏叶提取物的分子作用机制。 Fam20c激酶在调控炎症基因表达和胰岛素抵抗中的作用。3.我们将测试 假设脂肪特异性消融Fam20c可以逆转已建立的T2 DM。的总目标是 这些研究将阐明针对Fam20c的疗法如何用于恢复新陈代谢 2型糖尿病患者的健康状况。

Project Summary/Abstract Obesity and type 2 diabetes mellitus (T2DM) have become national and global epidemics. The rising prevalence of obesity has dramatically increased the burden of dyslipidemia, specific types of cancer, nonalcoholic fatty liver disease, T2DM and cardiovascular diseases, the leading cause of mortality in the country. Recent studies have highlighted the intimate links between metabolic diseases and adipose tissue inflammation. Adipose inflammation plays an integral role in the development of metabolic syndrome. Adipose-immune interactions can have both positive and negative effects on adipose tissue homeostasis and whole body metabolism. What initiates adipocyte dysfunction and the inflammatory processes in obesity remain an enigma. This research proposal seeks to understand the molecular mechanisms that underlie adipocyte dysfunction and adipose inflammation. We identify fam20c as a novel regulator of adipose tissue inflammation and insulin resistance. Obesity induces expression of fam20c in adipocytes. Conversely, ablation of fam20c in adipocytes ameliorates hyperglycemia. In this proposal, we seek to assess the mechanistic links between insulin resistance and inflammation. We will pursue the following specific aims: 1. Determine the physiological and cellular mechanisms by fam20c regulates energy balance, glucose homeostasis and adipose tissue inflammation. 2. Dissect the molecular mechanism of action of the fam20c kinase in regulating inflammatory gene expression and insulin resistance. 3. We will test the hypothesis that adipose-specific ablation of fam20c can reverse established T2DM. The overall goal of these studies will shed light on how therapies directed against fam20c can be used to restore metabolic health in patients with T2DM.