Genomic and non-genomic actions of androgens in regulation of fat mass and metabolism

雄激素在调节脂肪量和代谢中的基因组和非基因组作用

• 批准号: nhmrc : 454423
• 负责人: Dr Helen Maclean
• 金额: $ 26.37万
• 依托单位: The University of Melbourne
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/genomic-non-genomic-mass-metabolism/96915
• 关键词: Genomic; non; genomic; actions; androgens

Men have lower amounts of body fat than women, but are more likely to deposit fat around the stomach and abdominal region than women. This increased abdominal fat in men significantly increases the risk of developing type 2 diabetes and heart disease. The differences between men and women suggest that there is hormonal control of fat development; however, little is known regarding how male sex hormones, androgens, control these processes. We will investigate how androgens control fat formation, and the response of fat and muscle tissue to glucose and insulin, using mutant mouse strains. These mouse strains have a mutation in the androgen receptor, a protein which acts as a key-lock mechanism to allow tissues to respond to androgens. This mutation stops the androgen receptor from functioning, so these mice can be used to determine the function of androgens acting through the androgen receptor. We will study three strains of mutant mice: (i) in which the androgen receptor is non-functional in all tissues of the body; (ii) in which the androgen receptor is non-functional only in fat tissue, but normal in all other tissues; and (iii) in which the androgen receptor is non-functional only in skeletal muscle, but is normal in all other tissues. The aim of our research is to determine the effect of the mutations in these three different mouse lines on paramateres including the amount of fat formed, the site of fat deposition, the levels of lipids and insulin in the blood and their response to glucose. The androgen receptor is a master switch that turns on or off other genes. Therefore, we also aim to identify which genes are controlled by the androgen receptor in fat and muscle. This research will identify how androgens control fat development and function, and will identify genes that mediate these actions in fat and muscle. This will provide potential molecules that could be used therapeutically to treat obesity and prevent type 2 diabetes and heart disease.

男性的身体脂肪含量比女性低，但比女性更容易在胃和腹部周围沉积存款脂肪。男性腹部脂肪的增加会显著增加患2型糖尿病和心脏病的风险。男性和女性之间的差异表明，脂肪发育是由激素控制的;然而，关于男性性激素，雄激素如何控制这些过程，我们知之甚少。我们将研究雄激素如何控制脂肪的形成，以及脂肪和肌肉组织对葡萄糖和胰岛素的反应，使用突变小鼠品系。这些小鼠品系在雄激素受体中有突变，雄激素受体是一种蛋白质，它作为一种钥匙锁机制，允许组织对雄激素做出反应。这种突变使雄激素受体停止发挥作用，因此这些小鼠可用于确定通过雄激素受体发挥作用的雄激素的功能。我们将研究三种突变小鼠：（i）其中雄激素受体在身体的所有组织中都是无功能的;（ii）其中雄激素受体仅在脂肪组织中是无功能的，但在所有其他组织中是正常的;（iii）其中雄激素受体仅在骨骼肌中是无功能的，但在所有其他组织中是正常的。我们研究的目的是确定这三种不同小鼠品系中的突变对paramatees的影响，包括形成的脂肪量，脂肪沉积的部位，血液中脂质和胰岛素的水平及其对葡萄糖的反应。雄激素受体是开启或关闭其他基因的主开关。因此，我们的目标也是确定哪些基因是由脂肪和肌肉中的雄激素受体控制的。这项研究将确定雄激素如何控制脂肪的发育和功能，并将确定在脂肪和肌肉中介导这些作用的基因。这将提供潜在的分子，可用于治疗肥胖症和预防2型糖尿病和心脏病。