Castonguay T W, Beaulieu S, Eskay R L, Barden N, Kamara K, Khozin S, Lustberg L, Brown L
Department of Nutrition and Food Science, University of Maryland, College Park, MD 20742, USA.
Physiol Behav. 2002 Nov;77(2-3):417-23. doi: 10.1016/s0031-9384(02)00881-8.
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/3F1 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.
双侧肾上腺切除术（ADX）在几种动物模型中均可预防或减轻肥胖。表达糖皮质激素受体（GCR）反义RNA的小鼠会肥胖。本研究旨在检验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加速率和身体组成的影响。28只携带反义GCR构建体的雄性转基因小鼠和16只雄性B6C/3F1小鼠接受了双侧ADX手术或假手术。在手术时，部分ADX小鼠和所有假手术小鼠在肩胛下区域皮下植入了100毫克胆固醇（CHOL）药丸。其余ADX小鼠以CHOL为载体植入了100毫克1% w/w的ALDO药丸。所有小鼠放回笼中饲养2周。然后将它们断头并采集血液用于皮质酮、ALDO、胰岛素和瘦素的放射免疫测定。取出内脏并准备进行重量分析，包括弹式量热法。ADX导致转基因组和野生型组的胴体脂肪均显著下降。ALDO阻止了两组胴体脂肪的减少。ADX两周后，转基因小鼠与假手术的野生型对照组一样胖，而假手术组和ALDO处理的转基因组都明显更胖。尽管观察到ADX后胴体脂肪可靠地减少，但未发现循环瘦素相应减少。
