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

项目总结/摘要 肥胖和2型糖尿病（T2 DM）已成为国家和全球流行病。上升 肥胖症的流行显著增加了血脂异常，特定类型的癌症， 非酒精性脂肪肝、2型糖尿病和心血管疾病， 国家最近的研究强调了代谢疾病和脂肪组织之间的密切联系 炎症脂肪炎症在代谢综合征的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， 肥胖仍然是个谜。这项研究计划旨在了解分子机制， 是脂肪细胞功能障碍和脂肪炎症的基础。我们确定fam 20 c作为一种新的调节剂， 脂肪组织炎症和胰岛素抵抗。肥胖诱导脂肪细胞fam 20 c表达。 相反，脂肪细胞中fam 20 c的消融改善了高血糖症。在本建议中，我们力求 评估胰岛素抵抗和炎症之间的机制联系。我们将继续努力 具体目标：1.通过fam 20 c调节能量平衡来确定生理和细胞机制， 葡萄糖稳态和脂肪组织炎症。2.剖析了分子作用机制， fam 20 c激酶调节炎症基因表达与胰岛素抵抗3.我们将测试 脂肪特异性消融fam 20 c可以逆转已建立的T2 DM的假设。的总目标 这些研究将阐明如何利用针对FAM 20 C的疗法来恢复代谢， T2 DM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.