Androgen effects on adipose tissue architecture and function in nonhuman primates.
Androgen effects on adipose tissue architecture and function in nonhuman primates.
复制标题
DOI：
10.1210/en.2011-2111
复制
发表时间：
2012-04
期刊：
影响因子：
4.8
通讯作者：
O. Varlamov;Ashley E. White;J. Carroll;C. Bethea;A. Reddy;O. Slayden;R. O’Rourke;C. Roberts
中科院分区：
文献类型：
--
作者：
O. Varlamov;Ashley E. White;J. Carroll;C. Bethea;A. Reddy;O. Slayden;R. O’Rourke;C. Roberts
男性高雄激素血症和男性高雄激素血症与胰岛素抵抗和肥胖之间的差异表明，雄激素可能对脂肪和其他组织产生性别特异性影响，尽管其潜在机制仍知之甚少。此外，最近的研究还表明，啮齿动物和人类可能对雄激素失衡有不同的反应。为了更好地了解雄激素作用的临床相关性别特异性机制，我们使用非人灵长类动物研究性腺切除术和激素替代对白色脂肪组织的直接影响。我们还采用了一种新的离体方法，提供了一个方便的框架，在受控的组织培养环境下的脂肪组织生理学的理解。雄性动物体内雄激素剥夺不会导致明显的肥胖或胰岛素抵抗，但会诱导非常小的多室白色脂肪细胞的出现。睾酮替代恢复了正常细胞大小和单房表型，刺激了脂肪形成基因的转录，改善了男性脂肪组织的胰岛素敏感性。离体研究表明雄激素对脂肪细胞功能具有性别特异性影响。用雄激素治疗的女性脂肪组织显示基础升高，但胰岛素依赖性脂肪酸摄取减少。雄激素刺激的基础摄取是更大的卵巢切除女性的脂肪组织比完整的女性和卵巢切除女性体内雌激素和孕激素替代的脂肪组织。总的来说，这些数据表明，雄激素是必不可少的正常脂肪形成的男性，并能损害女性的基本脂肪细胞功能，从而加强了实验基础的性别特异性影响雄激素在脂肪组织。
The differential association of hypoandrogenism in men and hyperandrogenism in women with insulin resistance and obesity suggests that androgens may exert sex-specific effects on adipose and other tissues, although the underlying mechanisms remain poorly understood. Moreover, recent studies also suggest that rodents and humans may respond differently to androgen imbalance. To achieve better insight into clinically relevant sex-specific mechanisms of androgen action, we used nonhuman primates to investigate the direct effects of gonadectomy and hormone replacement on white adipose tissue. We also employed a novel ex vivo approach that provides a convenient framework for understanding of adipose tissue physiology under a controlled tissue culture environment. In vivo androgen deprivation of males did not result in overt obesity or insulin resistance but did induce the appearance of very small, multilocular white adipocytes. Testosterone replacement restored normal cell size and a unilocular phenotype and stimulated adipogenic gene transcription and improved insulin sensitivity of male adipose tissue. Ex vivo studies demonstrated sex-specific effects of androgens on adipocyte function. Female adipose tissue treated with androgens displayed elevated basal but reduced insulin-dependent fatty acid uptake. Androgen-stimulated basal uptake was greater in adipose tissue of ovariectomized females than in adipose tissue of intact females and ovariectomized females replaced with estrogen and progesterone in vivo. Collectively, these data demonstrate that androgens are essential for normal adipogenesis in males and can impair essential adipocyte functions in females, thus strengthening the experimental basis for sex-specific effects of androgens in adipose tissue.