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

男性的体脂量比女性低，但脂肪更容易堆积在胃部和腹部。男性腹部脂肪的增加显著增加了患2型糖尿病和心脏病的风险。男性和女性之间的差异表明，脂肪的发育是由激素控制的；然而，关于雄性激素如何控制这些过程，我们所知甚少。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。这些小鼠品系的雄激素受体发生了突变，雄激素受体是一种蛋白质，起着锁锁机制的作用，使组织能够对雄激素做出反应。这种突变阻止了雄激素受体的功能，所以这些老鼠可以用来确定雄激素通过雄激素受体发挥作用的功能。我们将研究三种突变小鼠：(i)雄激素受体在身体的所有组织中都不起作用；（ii）雄激素受体仅在脂肪组织中无功能，而在其他组织中均正常；（iii）雄激素受体仅在骨骼肌中无功能，但在其他所有组织中都正常。我们研究的目的是确定这三种不同小鼠系的突变对参数的影响，这些参数包括形成的脂肪量、脂肪沉积的位置、血液中脂质和胰岛素的水平以及它们对葡萄糖的反应。雄激素受体是开启或关闭其他基因的主开关。因此，我们还旨在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，预防2型糖尿病和心脏病。

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.