The effects of adrenalectomy and aldosterone replacement in transgenic mice expressing antisense RNA to the type 2 glucocorticoid receptor
The effects of adrenalectomy and aldosterone replacement in transgenic mice expressing antisense RNA to the type 2 glucocorticoid receptor
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DOI：
10.1016/s0031-9384(02)00881-8
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发表时间：
2002-11-01
影响因子：
2.9
通讯作者：
Brown, L
中科院分区：
文献类型：
--
作者：
Castonguay, TW;Beaulieu, S;Brown, L
双侧肾上腺切除术（ADX）在几种动物模型中预防或减轻肥胖。表达糖皮质激素受体（GCR）反义RNA的小鼠肥胖。本研究旨在探讨ADX和醛固酮（ALDO）替代对携带反义GCR基因构建体的小鼠体重增长率和体成分的影响。将28只携带反义GCR构建体的雄性转基因小鼠和16只雄性B6 C/3FI小鼠进行双侧ADX或假手术。在手术时，一些ADX小鼠和所有假手术小鼠在肩胛下区域皮下植入100 mg胆固醇（CHOL）颗粒。剩余的ADX小鼠植入100 mg 1% w/w ALDO颗粒，使用CHOL作为溶剂。将所有小鼠放回其饲养笼2周。然后将它们断头，收集血液用于皮质酮、ALDO、胰岛素和瘦素放射免疫测定。将尸体取出内脏，准备进行重量分析，包括弹式量热法。ADX导致转基因组和野生型组的胴体脂肪显著下降。ALDO阻止了两组动物的胴体脂肪减少。ADX后两周，转基因小鼠与假手术野生型对照组一样胖，而假手术组和ALDO治疗的转基因组明显更胖。尽管观察到ADX后胴体脂肪的可靠减少，但没有发现循环瘦素的相应减少。
Bilateral adrenalectomy (ADX) either prevents or attenuates obesity in several animal models. Mice that express an antisense RNA to the glucocorticoid receptor (GCR) are obese. The present study was conducted to examine the effects of ADX and aldosterone (ALDO) replacement on the rate of weight gain and body composition of mice bearing an antisense GCR gene construct. Twenty-eight male transgenic mice bearing the antisense GCR construct and 16 male B6C/3FI mice were either bilaterally ADX or given sham operations. At the time of surgery, some of the ADX mice and all of the sham-operated mice were implanted with 100-mg cholesterol (CHOL) pellets inserted subcutaneously in the subscapular region. The remaining ADX mice were implanted with 100-mg 1% w/w ALDO pellets using CHOL as vehicle. All mice were returned to their home cages for 2 weeks. They were then decapitated and the blood was collected for corticosterone, ALDO, insulin, and leptin radioimmunoassay. Carcasses were eviscerated and prepared for gravimetric analyses, including bomb calorimetry. ADX resulted in a significant drop in carcass fat in both transgenic and wildtype groups. ALDO prevented the decrease in carcass fat in both groups. Two weeks after ADX, transgenic mice were as fat as sham-operated wildtype controls, whereas both sham-operated and ALDO-treated transgenic groups were significantly fatter. Despite observing a reliable decrease in carcass fat following ADX, no corresponding decrease in circulating leptin was found. (C) 2002 Published by Elsevier Science Inc.