Yu I-Chen, Lin Hung-Yun, Liu Ning-Chun, Wang Ruey-Shen, Sparks Janet D, Yeh Shuyuan, Chang Chawnshang
Department of Pathology, George Whipple Laboratory for Cancer Research, and the Cancer Center, University of Rochester Medical Center, Rochester, New York 14642, USA.
Endocrinology. 2008 May;149(5):2361-8. doi: 10.1210/en.2007-0516. Epub 2008 Feb 14.
Insulin resistance occurs through an inadequate response to insulin by insulin target organs such as liver, muscle, and adipose tissue with consequent insufficient glucose uptake. In previous studies we demonstrated that whole body androgen receptor (AR) knockout (AR(-/y)) mice develop obesity and exhibit insulin and leptin resistance at advanced age. By examining adipose tissue-specific AR knockout (A-AR(-/y)) mice, we found A-AR(-/y) mice were hyperleptinemic but showed no leptin resistance, although body weight and adiposity index of A-AR(-/y) mice were identical with those of male wild-type control mice. Hypotriglyceridemia and hypocholesterolemia found in nonobese A-AR(-/y) mice suggested a beneficial effect of high leptin levels independent of fat deposition. Further examination showed that androgen-AR signaling in adipose tissue plays a direct regulatory role in leptin expression via enhanced estrogen receptor transactivation activity due to elevated intraadipose estrogens. The present study in A-AR(-/y) mice suggests a differential tissue-specific role of AR in energy balance control in males.
胰岛素抵抗是由于肝脏、肌肉和脂肪组织等胰岛素靶器官对胰岛素反应不足，导致葡萄糖摄取不足而发生的。在先前的研究中，我们证明全身雄激素受体（AR）敲除（AR(-/y)）小鼠会出现肥胖，并在老年时表现出胰岛素和瘦素抵抗。通过研究脂肪组织特异性AR敲除（A-AR(-/y)）小鼠，我们发现A-AR(-/y)小鼠瘦素水平过高，但未表现出瘦素抵抗，尽管A-AR(-/y)小鼠的体重和肥胖指数与雄性野生型对照小鼠相同。在非肥胖的A-AR(-/y)小鼠中发现的低甘油三酯血症和低胆固醇血症表明，高瘦素水平具有独立于脂肪沉积的有益作用。进一步研究表明，脂肪组织中的雄激素-AR信号通路通过增强雌激素受体反式激活活性，对瘦素表达起直接调节作用，这是由于脂肪组织内雌激素水平升高所致。本研究对A-AR(-/y)小鼠的研究表明，AR在雄性能量平衡控制中具有不同的组织特异性作用。
