Differential effects of refeeding on melanocortin-responsive neurons in the hypothalamic paraventricular nucleus
Differential effects of refeeding on melanocortin-responsive neurons in the hypothalamic paraventricular nucleus
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DOI：
10.1210/en.2008-0411
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发表时间：
2008-09-01
期刊：
影响因子：
4.8
通讯作者：
Lechan, Ronald M.
中科院分区：
文献类型：
--
作者：
Sanchez, Edith;Singru, Praful S.;Lechan, Ronald M.
为了探究再进食对下丘脑室旁核（PVN）中促甲状腺激素释放激素（TRH）基因表达恢复的影响及其与弓状核（ARC）中进食相关神经肽的相关性，我们对长时间禁食的斯普拉格 - 道利大鼠研究了再进食2小时后PVN和ARC中的c - fos免疫反应性（IR），以及再进食4、12和24小时后下丘脑TRH、神经肽Y（NPY）和刺鼠相关蛋白（AGRP）的mRNA水平。尽管如ARC中α - 黑素细胞刺激素（α - MSH） - IR神经元和腹侧小细胞亚区PVN神经元的c - fos IR所表明的那样，再进食可使阿黑皮素原神经元迅速重新激活，但在促垂体的TRH神经元中仅有9.7 ± 1.1%存在c - fos IR。再进食开始后4小时和12小时，血清促甲状腺激素（TSH）水平仍然受到抑制，24小时后恢复到进食水平。与进食的动物相比，禁食降低了TRH mRNA水平，并且与TSH相似，再进食后4小时和12小时仍然受到抑制，24小时时恢复正常。禁食大鼠ARC中AGRP和NPY基因表达显著升高，再进食12小时后AGRP mRNA恢复到基线水平，而NPY mRNA即使在24小时时仍然持续升高。这些数据提示，再进食诱导的黑皮质素信号激活对PVN中的靶神经元产生不同作用，早期作用于可能参与饱腹感的神经元，后期作用于参与能量消耗的促垂体TRH神经元，可能由AGRP和NPY的持续升高介导。这种反应可能是一种重要的内稳态机制，允许补充与禁食相关的耗尽的能量储备。
To explore the effect of refeeding on recovery of TRH gene expression in the hypothalamic paraventricular nucleus (PVN) and its correlation with the feeding-related neuropeptides in the arcuate nucleus (ARC), c-fos immunoreactivity (IR) in the PVN and ARC 2 h after refeeding and hypothalamic TRH, neuropeptide Y (NPY) and agouti-related protein (AGRP) mRNA levels 4, 12, and 24 h after refeeding were studied in Sprague-Dawley rats subjected to prolonged fasting. Despite rapid reactivation of proopiomelanocortin neurons by refeeding as demonstrated by c-fos IR in ARC alpha-MSH-IR neurons and ventral parvocellular subdivision PVN neurons, c-fos IR was present in only 9.7 +/- 1.1% hypophysiotropic TRH neurons. Serum TSH levels remained suppressed 4 and 12 h after the start of refeeding, returning to fed levels after 24 h. Fasting reduced TRH mRNA compared with fed animals, and similar to TSH, remained suppressed at 4 and 12 h after refeeding, returning toward normal at 24 h. AGRP and NPY gene expression in the ARC were markedly elevated in fasting rats, AGRP mRNA returning to baseline levels 12 h after refeeding and NPY mRNA remaining persistently elevated even at 24 h. These data raise the possibility that refeeding-induced activation of melanocortin signaling exerts differential actions on its target neurons in the PVN, an early action directed at neurons that may be involved in satiety, and a later action on hypophysiotropic TRH neurons involved in energy expenditure, potentially mediated by sustained elevations in AGRP and NPY. This response may be an important homeostatic mechanism to allow replenishment of depleted energy stores associated with fasting.