Glucocorticoids, the etiology of obesity and the metabolic syndrome
Glucocorticoids, the etiology of obesity and the metabolic syndrome
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DOI：
10.2174/156720507780362236
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发表时间：
2007-04-01
影响因子：
2.1
通讯作者：
Foster, Michelle T.
中科院分区：
文献类型：
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作者：
Dallman, Mary F.;Akana, Susan F.;Foster, Michelle T.
在哺乳动物中，糖皮质激素的作用似乎已经进化到维持和增强能量储存，以用于挽救生命的再生。它们作用于大脑以刺激搜索行为、可口的进食和情感相关的记忆，它们作用于身体以调动储存的外周能量并将其引导到服务于肝脏基质需求的中央仓库。我们在大鼠中的研究表明，皮质酮以剂量相关的方式刺激寻找和摄入可口的食物（蔗糖、糖精和猪油）。肾上腺切除大鼠体重增加不佳，脂肪含量低，交感神经和下丘脑-垂体-肾上腺流出增加，行为改变。用皮质酮替代可逆转这些效应。令人惊讶的是，当给这些大鼠提供30%的蔗糖饮用时，除了盐水之外，肾上腺切除术的所有常见影响都在没有皮质酮的情况下得到纠正。我们假设有一个代谢反馈系统，降低应激反应。虽然我们还没有确定与蔗糖饮用相关的信号，肠系膜脂肪的重量与下丘脑促肾上腺皮质激素释放因子（CRF）呈负相关。当大鼠随意食用猪油和蔗糖时，脂肪储存增加，CRF、ACTH和皮质酮反应降低。在压力下，食物的摄入量减少，但猪油和蔗糖的摄入量不会减少。我们目前的工作模型表明，来自脂肪储存的适口性信号和神经信号作用于大脑，以减少中枢应激反应系统的活动。临床研究的相关结果支持糖皮质激素的微小变化在2型糖尿病中的强大作用。
In mammals, glucocorticoid actions appear to have evolved to maintain and enhance energy stores to be used for life-saving gluconeogenesis. They act on the brain to stimulate search behaviors, palatable feeding and emotionally relevant memories, and they act on the body to mobilize stored peripheral energy and direct it to central depots that serve the substrate needs of the liver. Our work in rats shows that searching and intake of palatable foods (sucrose, saccharin and lard) are stimulated by corticosterone in a dose-related fashion. Adrenalectomized rats gain weight poorly, have low fat content, increased sympathetic neural and hypothalamo-pituitary-adrenal outflow, and altered behaviors. Replacement with corticosterone reverses these effects. Surprisingly, when such rats are provided with 30% sucrose to drink, in addition to saline, all of the usual effects of adrenalectomy are corrected without corticosterone. We hypothesize that there is a metabolic feedback system that decreases stress-responsiveness. Although we have not yet identified the signal associated with sucrose drinking, the weight of mesenteric fat correlates inversely with hypothalamic corticotropin-releasing factor (CRF). When rats eat lard and sucrose ad libitum, fat stores increase and CRF, ACTH and corticosterone responses are reduced. During stress, chow intake decreases but intake of lard and sucrose does not. Our current working model suggests that palatability signals and neural signals from fat stores act on brain to reduce activity in the central stress response system. Correlative results from a clinical study support the powerful role of small changes in glucocorticoids in type 2 diabetes.