STAT5 as an anti-obesity agent

STAT5 作为抗肥胖剂

• 批准号: nhmrc : 401668
• 负责人: Prof Michael Waters
• 金额: $ 33.71万
• 依托单位: The University of Queensland
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2006
• 资助国家: 澳大利亚
• 起止时间: 2006-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/stat5-an-anti-obesity-agent/99896
• 关键词: STAT5; anti; obesity; agent

An obesity epidemic is evident in first world countries including Australia. Twenty seven percent of men aged 55-64 in this country are obese. Obesity results in increased mortality and morbidity from type 2 diabetes, cardiovascular disease, renal disease and endometrial cancer, among others. Given our flaccid lifestyles, it is imperative that the metabolic processes underlying obesity be fully understood, to allow development of suitable treatment modalities. This proposal seeks to establish an important new element in our understanding of the development of obesity, the transcription factor STAT5. With previous NHMRC support, we developed sophisticated genetically modified mice which lack defined signalling processes initiated by growth hormone, an anti-obesity agent. These studies showed a strong correlation between ability to activate STAT5 and resistance to obesity. There is fragmentary literature evidence to support our hypothesis, which could also explain some of leptins anti-obesity actions. Using mice which lack STAT5, we shall establish a role for STAT5 as an antiobesity agent. The actions of STAT5 are normally blocked by feedback inhibitors referred to as SOCS, discovered by Australians. We shall define which SOCS is the feedback regulator for obesity control, allowing us to develop specific anti-SOCS agents which will act as novel anti-obesity agents.

肥胖流行病在包括澳大利亚在内的第一世界国家很明显。在这个国家，27%的55-64岁的男性肥胖。肥胖导致2型糖尿病、心血管疾病、肾病和子宫内膜癌等疾病的死亡率和发病率增加。鉴于我们软弱的生活方式，必须充分了解肥胖的代谢过程，以开发合适的治疗方式。这项提案旨在建立一个重要的新元素，我们的理解肥胖的发展，转录因子STAT 5。在NHMRC先前的支持下，我们开发了复杂的转基因小鼠，这些小鼠缺乏由生长激素（一种抗肥胖剂）启动的明确信号传导过程。这些研究表明，激活STAT 5的能力与抵抗肥胖之间存在很强的相关性。有零星的文献证据支持我们的假设，这也可以解释leptins的一些减肥作用。使用缺乏STAT 5的小鼠，我们将建立STAT 5作为抗肥胖剂的作用。STAT 5的作用通常会被澳大利亚人发现的反馈抑制剂（称为SOCS）阻止。我们将定义哪些SOCS是肥胖控制的反馈调节剂，使我们能够开发特定的抗SOCS药物，作为新的抗肥胖药物。