Dallman Mary F, Akana Susan F, Pecoraro Norman C, Warne James P, la Fleur Susanne E, Foster Michelle T
Department of Physiology, UCSF, San Francisco, CA 94143-0444, USA.
Curr Alzheimer Res. 2007 Apr;4(2):199-204. doi: 10.2174/156720507780362236.
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.
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备，以用于挽救生命的糖异生过程。它们作用于大脑，刺激搜寻行为、美味进食和与情绪相关的记忆，并且作用于身体，动员储存的外周能量，并将其导向为肝脏提供底物的中央储存库。我们在大鼠身上的研究表明，皮质酮以剂量相关的方式刺激对美味食物（蔗糖、糖精和猪油）的搜寻和摄取。肾上腺切除的大鼠体重增加缓慢，脂肪含量低，交感神经和下丘脑-垂体-肾上腺轴的输出增加，行为也发生改变。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%的蔗糖溶液饮用（除生理盐水外）时，肾上腺切除的所有常见效应在没有皮质酮的情况下也得到了纠正。我们假设存在一种代谢反馈系统，可降低应激反应性。虽然我们尚未确定与饮用蔗糖相关的信号，但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。当大鼠随意进食猪油和蔗糖时，脂肪储备增加，CRF、促肾上腺皮质激素（ACTH）和皮质酮的反应降低。在应激期间，普通食物的摄入量减少，但猪油和蔗糖的摄入量不变。我们目前的工作模型表明，美味信号和来自脂肪储备的神经信号作用于大脑，以降低中枢应激反应系统的活性。一项临床研究的相关结果支持了糖皮质激素的微小变化在2型糖尿病中的重要作用。
