Department of Cancer Biology, Beckman Research Institute, City of Hope, Duarte, CA, USA.
J Steroid Biochem Mol Biol. 2013 Nov;138:100-6. doi: 10.1016/j.jsbmb.2013.04.001. Epub 2013 May 7.
To better understand how elevated androgen levels regulate food intake and obesity in females, we treated ovariectomized female mice with dihydrotestosterone (DHT) (non-aromatazable androgen), measured food intake and body weight, and evaluated physiological changes in liver function, glucose tolerance, and leptin resistance. Ovariectomized mice were treated with DHT or placebo. Mice were then fed a high fat diet under free-feeding or pair-feeding conditions for 3 months. We found that when DHT-treated ovariectomized mice had free access to food (free-feeding), they had increased food intake and higher body weight compared with control animals. These mice also had a significantly greater accumulation of fat in the liver and exhibited increased fasting glucose, impaired glucose tolerance, and resistance to leptin. However, when these mice were placed on a restricted diet and fed the same caloric amounts as controls (pair-feeding), their body weight increased at the same rate as control animals. This suggests that androgen regulates food intake through altered leptin sensitivity, and this increase of food intake could significantly contribute to an obesity phenotype. In summary, we demonstrated a role for androgen in the regulation of food intake and weight gain in females using a mouse model. This model will be useful to further elucidate the role of elevated androgen in females.
为了更好地了解升高的雄激素水平如何调节女性的食物摄入和肥胖，我们用二氢睾酮（DHT）（非芳香化雄激素）处理去卵巢雌性小鼠，测量食物摄入和体重，并评估肝功能、葡萄糖耐量和瘦素抵抗的生理变化。去卵巢小鼠用 DHT 或安慰剂处理。然后，让小鼠在自由喂养或配对喂养条件下进食高脂肪饮食 3 个月。我们发现，当 DHT 处理的去卵巢小鼠可以自由进食（自由喂养）时，与对照动物相比，它们的食物摄入量增加，体重增加。这些小鼠的肝脏脂肪堆积明显增加，表现为空腹血糖升高、葡萄糖耐量受损和对瘦素的抵抗。然而，当这些小鼠被限制饮食并摄入与对照组相同的热量时（配对喂养），它们的体重增加速度与对照组相同。这表明雄激素通过改变瘦素敏感性来调节食物摄入，而这种食物摄入量的增加可能会显著导致肥胖表型。总之，我们使用小鼠模型证明了雄激素在女性食物摄入和体重增加中的调节作用。该模型将有助于进一步阐明升高的雄激素在女性中的作用。
