Androgen receptor null male mice develop late-onset obesity caused by decreased energy expenditure and lipolytic activity but show normal insulin sensitivity with high adiponectin secretion
Androgen receptor null male mice develop late-onset obesity caused by decreased energy expenditure and lipolytic activity but show normal insulin sensitivity with high adiponectin secretion
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DOI：
10.2337/diabetes.54.4.1000
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发表时间：
2005-04-01
期刊：
影响因子：
7.7
通讯作者：
Nawata, H
中科院分区：
文献类型：
--
作者：
Fan, WQ;Yanase, T;Nawata, H
雄激素受体（AR）基因敲除雄性小鼠（AR（L-/Y））表现出迟发性肥胖，这一点通过基于计算机断层扫描的身体成分分析得到证实。与野生型雄性（AR（X/Y））对照组相比，AR（L-/Y）小鼠是欣快的，但它们也缺乏活力，消耗的氧气也较少。转录谱分析表明，AR（L-/Y）小鼠的产热解偶联蛋白1的转录本较低，随后发现该蛋白被AR配体依赖性激活。我们还发现，与AR（X/Y）小鼠相比，在白色脂肪组织中，脂联素（胰岛素增敏）的分泌增强，过氧化物酶体增殖物激活受体-γ的表达相对较低。这两个因素都可以解释为什么AR（L-/Y）小鼠的整体胰岛素敏感性保持不变，尽管它们明显肥胖。结果表明，AR通过影响能量平衡在男性代谢中起重要作用，并与肥胖和胰岛素敏感性呈负相关。
Androgen receptor (AR) null male mice (AR(L-/Y)) revealed late-onset obesity, which was confirmed by computed tomography-based body composition analysis. AR(L-/Y) mice were euphagic compared with the wild-type male (AR(X/Y)) controls, but they were also less dynamic and consumed less oxygen. Transcript profiling indicated that AR(L-/Y) mice had lower transcripts for the thermogenetic uncoupling protein 1, which was subsequently found to be ligand-dependently activated by AR. We also found enhanced secretion of adiponectin, which is insulin sensitizing, from adipose tissue and a relatively lower expression of peroxisome proliferator-activated receptor-gamma in white adipose tissue in comparison to AR(X/Y) mice. Both factors might explain why the overall insulin sensitivity of AR(L-/Y) mice remained intact, despite their apparent obesity. The results revealed that AR plays important roles in male metabolism by affecting the energy balance, and it is negative to both adiposity and insulin sensitivity.