The Role of Extracellular Environment in Adipocyte Fate

细胞外环境在脂肪细胞命运中的作用

基本信息

批准号：
10396224
负责人：
Maria Alejandra Gonzalez Porras
金额：
$ 0.25万
依托单位：
UNIVERSITY OF TEXAS SAN ANTONIO
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-05-01 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10396224
关键词：
3-Dimensional Adhesions Adipocytes Adipose tissue American Biochemical Biocompatible Materials Biomedical Engineering Cardiovascular Diseases Cell Communication Cells Characteristics Chronic Collagen Communication Data Disease Energy Intake Energy Metabolism Environment Environmental Risk Factor Event Exhibits Extracellular Matrix Fatty acid glycerol esters Fiber Genes Goals Healthcare Homeostasis Human Hypertrophy Insulin Resistance Integrins Knock-out Knowledge Laboratories Laminin Lipids Maintenance Mammals Mechanics Mediating Medical Mentors Metabolic Metabolic Diseases Mitochondria Morbidity - disease rate Mus Non-Insulin-Dependent Diabetes Mellitus Obesity Obesity Epidemic Organ Outcome Pathologic Physiological Physiology Play Population Preparation Property Proteins Proteoglycan Public Health Research Resistance Role Signal Transduction Structure System Therapeutic Thermogenesis Tissues Wild Type Mouse Work Writing base blood glucose regulation career career development cell behavior experience extracellular fibrous protein improved in vivo insight insulin sensitivity interstitial mechanical properties mechanotransduction mortality nanoparticle new therapeutic target novel null mutation skills stem cells subcutaneous targeted delivery therapeutic development therapeutic target uncoupling protein 1

项目摘要

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.

项目摘要肥胖是能量摄入和能量消耗之间能量稳态的长期失衡，是公众健康危机并继续成为美国最重要的医疗挑战之一。肥胖会造成每年在美国医疗保健方面的负担超过1900亿美元。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。哺乳动物中有两种类型的脂肪组织：白色脂肪专门用于储能的组织和热脂肪组织专门用于能量支出和热发生。热脂肪组织已被证明具有反相关性肥胖，这意味着有可能通过增加全身能量消耗热脂肪组织的数量和/或活性。因此，改变脂肪的热能力可能是包括肥胖症在内的代谢疾病的治疗。靶向热脂肪组织的新疗法已有由于对如何维持转化的脂肪组织在体内的维护，部分原因是对如何了解如何环境因素控制脂肪细胞的命运和维护。这项研究工作旨在了解角色脂肪细胞命运中的细胞外基质相互作用（ECM）的此信息将确定新的治疗性肥胖和代谢疾病的靶标。更好地理解这些原因的根本原因热脂肪的特征将使我们能够专门操纵这些细胞以改善全身能量代谢和葡萄糖稳态，并探索合成底物，以增加形成热脂肪组织。