The Role of Extracellular Environment in Adipocyte Fate

项目摘要 肥胖是一种能量摄入和能量消耗之间的能量稳态的慢性失衡， 健康危机，并继续成为美国最重要的医疗挑战之一。 每年给美国医疗保健带来超过1900亿美元的负担。治疗方法的发展 减少或消除与肥胖相关的发病率和死亡率将对 美国人口和医疗保健支出。哺乳动物的脂肪组织有两种：白色脂肪 专门用于能量储存的组织和专门用于能量储存的产热脂肪组织 消耗和产热。生热脂肪组织已被证明具有负相关性 肥胖，这意味着它可能会增加全身的能量消耗，通过增加 产热脂肪组织的数量和/或活性。因此，改变脂肪产热能力可能是一种 治疗代谢性疾病，包括肥胖症。针对产热脂肪组织的新疗法 在体内维持转化的脂肪组织失败，部分原因是对如何转化的理解有限。 环境因素控制脂肪细胞的命运和维持。这项研究旨在了解 细胞外基质相互作用（ECM）在脂肪细胞的命运。这些信息将确定新的治疗方法 肥胖症和代谢疾病的治疗目标。更好地了解这些问题的根本原因 产热脂肪的特性将使我们能够专门操纵这些细胞，以提高全身能量 代谢和葡萄糖稳态，并探索合成底物，增加形成 产热脂肪组织

Project Summary Obesity, a chronic imbalance in energy homeostasis between energy intake and energy expenditure, is a public health crisis and continues to be among the most important medical challenges in the U.S.A. Obesity creates a greater than $190 billion burden annually on American healthcare. The development of therapeutic approaches that lessen or eliminate obesity-associated morbidity and mortality would have a transformative impact on the American population and healthcare spending. There are two types of adipose tissue in mammals: white adipose tissue which is specialized for energy storage, and thermogenic adipose tissue specialized for energy expenditure and thermogenesis. Thermogenic adipose tissue has been shown to have an inverse correlation with adiposity, meaning that it might be possible to increase whole-body energy expenditure by increasing the number and/or activity of thermogenic adipose tissue. Thus, altering adipose thermogenic capacity could be a treatment for metabolic diseases, including obesity. New therapies targeting thermogenic adipose tissue have failed in maintaining transformed adipose tissue in-vivo, in part, due to the limited understanding of how environmental factors control adipocyte fate and maintenance. This research effort aims to understand the role of the extracellular matrix interaction (ECM) in the fate of adipocytes. This information will identify new therapeutic targets for obesity and metabolic diseases. A better understanding of the underlying causes of these characteristics for thermogenic fat will allow us to specifically manipulate these cells to improve systemic energy metabolism and glucose homeostasis, and to explore synthetic substrates that increase formation of thermogenic adipose tissue.