Endocrine and Physiological Changes in Response to Chronic Corticosterone: A Potential Model of the Metabolic Syndrome in Mouse
Endocrine and Physiological Changes in Response to Chronic Corticosterone: A Potential Model of the Metabolic Syndrome in Mouse
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DOI：
10.1210/en.2009-1436
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发表时间：
2010-05-01
期刊：
影响因子：
4.8
通讯作者：
McEwen, Bruce S.
中科院分区：
文献类型：
--
作者：
Karatsoreos, Ilia N.;Bhagat, Sarah M.;McEwen, Bruce S.
许多临床和实验研究已经将压力与包括代谢紊乱在内的生理综合征的发展相关的风险因素的变化联系起来。应激反应的不同介质，如皮质酮（CORT），如何影响这些风险的变化仍不清楚。虽然CORT具有有益的短期效应，但长期暴露于CORT可导致其急性保护的生理系统受损。从抑郁症到库欣综合征，在许多不同的疾病中观察到这一重要生理信号的中断。因此，了解慢性高CORT对代谢和生理的影响至关重要。本实验观察了饮水中CORT染毒4周对雄性小鼠生理和行为的影响。我们使用这种方法作为一种非侵入性的方式来改变血浆CORT水平，同时保持正常动物昼夜节律的一些完整性。这种方法优于涉及恒定CORT丸，CORT注射或肾上腺切除术的方法。我们发现，高剂量的CORT（100 μ g/ml）导致体重增加，肥胖增加，血浆瘦素，胰岛素和甘油三酯水平升高，食欲过盛，并减少家庭笼运动的快速和戏剧性的增加。较低剂量的CORT（25 μ g/ml）导致这些措施中的一些中间表型，但对其他没有影响。我们认为，在高CORT动物中观察到的生理变化近似于在患有代谢综合征的个体中观察到的变化，并且它们可能作为高皮质醇血症和应激相关肥胖的模型。（内分泌学151：2117-2127，2010）
Numerous clinical and experimental studies have linked stress to changes in risk factors associated with the development of physiological syndromes, including metabolic disorders. How different mediators of the stress response, such as corticosterone (CORT), influence these changes in risk remains unclear. Although CORT has beneficial short-term effects, long-term CORT exposure can result in damage to the physiological systems it protects acutely. Disruption of this important physiologic signal is observed in numerous disparate disorders, ranging from depression to Cushing's syndrome. Thus, understanding the effects of chronic high CORT on metabolism and physiology is of key importance. We explored the effects of 4-wk exposure to CORT dissolved in the drinking water on the physiology and behavior of male mice. We used this approach as a noninvasive way of altering plasma CORT levels while retaining some integrity in the diurnal rhythm present in normal animals. This approach has advantages over methods involving constant CORT pellets, CORT injections, or adrenalectomy. We found that high doses of CORT (100 mu g/ml) result in rapid and dramatic increases in weight gain, increased adiposity, elevated plasma leptin, insulin and triglyceride levels, hyperphagia, and decreased home-cage locomotion. A lower dose of CORT (25 mu g/ml) resulted in an intermediate phenotype in some of these measures but had no effect on others. We propose that the physiological changes observed in the high-CORT animals approximate changes observed in individuals suffering from the metabolic syndrome, and that they potentially serve as a model for hypercortisolemia and stress-related obesity. (Endocrinology 151: 2117-2127, 2010)