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: 6105566
• 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/6105566
• 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 studied situation in which excess fat causes diabetes.

我们正在研究能量的生理学 体内平衡及其在肥胖和糖尿病中的作用。我们整合 分子生物学与生理学，主要使用小鼠作为 模型系统。一个研究重点是瘦素，一种由 脂肪细胞对于适应饥饿和 能量消耗和肥胖的反馈调节。我们是 表征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 调节瘦素转录。由于能量消耗对于 防御肥胖，能量消耗也是一个兴趣。 我们发现了一个基因，解偶联蛋白 3 (ucp3)，它是 在肌肉和脂肪组织中表达。 Ucp3 同源于 ucp1，它负责将能量“浪费”为热量。 Ucp3 是 受甲状腺激素、β3-肾上腺素能激动剂和禁食调节 因此可能会调节能量消耗的一些变化 由这些因素/条件引起。第三条调查线是 缺乏白色脂肪的转基因小鼠。这款鼠标是一个很好的模型 患有脂肪萎缩性糖尿病的人。我们正在研究这些小鼠 尝试了解缺乏脂肪如何导致糖尿病，这是一种 与更多研究的情况形成有趣的对比，在这种情况下，多余的脂肪 导致糖尿病。