Induction of obesity and hyperleptinemia by central glucocorticoid infusion in the rat
Induction of obesity and hyperleptinemia by central glucocorticoid infusion in the rat
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DOI：
10.2337/diabetes.48.2.365
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发表时间：
1999-02-01
期刊：
影响因子：
7.7
通讯作者：
Rohner-Jeanrenaud, F
中科院分区：
文献类型：
--
作者：
Zakrzewska, KE;Cusin, I;Rohner-Jeanrenaud, F
已经声称，有利于动物或人肥胖的发展或维持的因素可能包括糖皮质激素产生的增加或下丘脑-垂体-肾上腺轴的高反应性。在正常大鼠中，糖皮质激素已被证明是神经肽Y的慢性脑室内输注所必需的，以产生肥胖和相关异常。相反，糖皮质激素抑制瘦素的减肥作用。糖皮质激素的这种双重作用可能发生在中枢神经系统内，因为神经肽Y和瘦素都在下丘脑内起作用。本研究的目的是确定脑室内给予糖皮质激素（地塞米松）对正常大鼠体重稳态和下丘脑神经肽Y和促肾上腺皮质激素释放激素水平的影响。连续中枢糖皮质激素输注3天导致相对于盐水输注对照组的食物摄入量和体重显著持续增加。输注消除内源性皮质酮输出，并产生高胰岛素血症、高脂血症和高瘦素血症，这是肥胖综合征的三种显著异常。中枢糖皮质激素输注也使棕色脂肪组织中解偶联蛋白（UCP）-1和UCP-3以及肌肉中UCP-3的表达显著降低。最后，慢性中枢糖皮质激素给药增加了下丘脑神经肽Y的水平，降低了促肾上腺皮质激素释放激素的水平。当外周给予相同剂量的糖皮质激素时，它导致食物摄入量和体重减少，与下丘脑神经肽Y水平的降低保持一致。这些结果表明，糖皮质激素诱导的肥胖综合征在啮齿类动物的作用集中，而不是外周。
It has been claimed that factors favoring the development or maintenance of animal or human obesity may include increases in glucocorticoid production or hyperresponsiveness of the hypothalamic-pituitary-adrenal axis. In normal rats, glucocorticoids have been shown to be necessary for chronic intracerebroventricular infusion of neuropeptide Y to produce obesity and related abnormalities. Conversely, glucocorticoids inhibited the body weight-lowering effect of leptin. Such dual action of glucocorticoids may occur within the central nervous system, since both neuropeptide Y and leptin act within the hypothalamus. The aim of this study was to determine the effects of glucocorticoids (dexamethasone) given intracerebroventricularly to normal rats on body weight homeostasis and hypothalamic levels of neuropeptide Y and corticotropin-releasing hormone. Continuous central glucocorticoid infusion for 3 days resulted in marked sustained increases in food intake and body weight relative to saline-infused controls. The infusion abolished endogenous corticosterone output and produced hyperinsulinemia, hypertriglyceridemia, and hyperleptinemia, three salient abnormalities of obesity syndromes. Central glucocorticoid infusion also produced a marked decrease in the expression of uncoupling protein (UCP)-1 and UCP-3 in brown adipose tissue and UCP-3 in muscle. Finally, chronic central glucocorticoid administration increased the hypothalamic levels of neuropeptide Y and decreased those of corticotropin-releasing hormone. When the same dose of glucocorticoids was administered peripherally, it resulted in decreases in food intake and body weight, in keeping with the decrease in hypothalamic neuropeptide Y levels. These results suggest that glucocorticoids induce an obesity syndrome in rodents by acting centrally and not peripherally.