REGULATION OF GENE EXPRESSION RELEVANT TO THE ADIPOSE CELL AND OBESITY

脂肪细胞与肥胖相关基因表达的调控

• 批准号: 6289802
• 负责人: MARC L REITMAN
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6289802
• 关键词: adipose tissue; bioenergetics; diabetes mellitus; diabetes mellitus genetics; gene induction /repression; genetic promoter element; glucocorticoids; hormone receptor; hormone regulation /control mechanism; hormones; intermolecular interaction; laboratory mouse; leptin; nucleic acid sequence; nutrition related tag; obesity; transcription factor

We are investigating the physiology of energy homeostasis and its role in obesity and diabetes. We integrate molecular biology with physiology, chiefly using the mouse as a model system. One research focus is on leptin, a hormone made in adipose cells that is important for adaptation to starvation and in feedback regulation of energy expenditure and adiposity. We are characterizing the transcription factors controlling leptin expression and how the cell type, level of adipose stores, and hormonal milieu regulate leptin transcription. Since energy expenditure is crucial to the defense against obesity, energy expenditure is also an interest. We discovered a gene, uncoupling protein-3 (ucp3) that is expressed in muscle and adipose tissue. Ucp3 is homologous to ucp1, which is responsible for wasting energy as heat. Ucp3 is regulated by thyroid hormone, beta3-adrenergic agonist, and fasting and thus may mediate some of the changes in energy expenditure caused by these agents/conditions. A third line of investigation is a transgenic mouse lacking white fat. This mouse is a good model of humans with lipoatrophic diabetes. We are studying these mice to try to understand how the lack of fat causes diabetes, which is an intriguing contrast to the more common situation in which excess fat causes diabetes. - leptin, uncoupling proteins, diabetes, obesity, lipoatrophy, indirect calorimetry, metabolism, mice

我们正在研究能量动态平衡的生理学及其在肥胖和糖尿病中的作用。我们把分子生物学和生理学结合起来，主要是用小鼠作为模型系统。其中一个研究重点是瘦素，这是一种在脂肪细胞中产生的荷尔蒙，对适应饥饿以及反馈调节能量消耗和肥胖非常重要。我们正在研究控制瘦素表达的转录因子，以及细胞类型、脂肪储存水平和激素环境如何调控瘦素转录。由于能量消耗对对抗肥胖至关重要，因此能量消耗也是一种兴趣。我们发现了一个基因，解偶联蛋白-3(UCP3)，它在肌肉和脂肪组织中表达。UCP3与UCP1同源，UCP1负责将能量浪费为热量。UCP3受甲状腺激素、β3-肾上腺素能激动剂和禁食的调节，因此可能调节这些因素/条件引起的能量消耗的一些变化。第三个研究方向是缺乏白色脂肪的转基因小鼠。这只小鼠是人类脂肪萎缩性糖尿病的良好模型。我们正在研究这些小鼠，试图了解缺乏脂肪是如何导致糖尿病的，这与更常见的情况--过量脂肪导致糖尿病--形成了有趣的对比。-瘦素，解偶联蛋白，糖尿病，肥胖，脂肪萎缩，间接量热法，代谢，小鼠