Intracerebroventricular C75 decreases meal frequency and reduces AgRP gene expression in rats
Intracerebroventricular C75 decreases meal frequency and reduces AgRP gene expression in rats
复制标题
DOI：
10.1152/ajpregu.00041.2006
复制
发表时间：
2006-07-01
影响因子：
2.8
通讯作者：
McFadden, Jill M.
中科院分区：
文献类型：
--
作者：
Aja, Susan;Bi, Sheng;McFadden, Jill M.
3-羧基-4-烷基-2-亚甲基丁内酯(C75)是一种脂肪酸合成酶抑制剂和肉碱棕榈酰基转移酶-1的刺激物，在系统或中枢给药时，可减少啮齿动物的摄食量和体重。细胞内的分子机制涉及细胞能量状态的改变，以启动摄食和体重减轻。然而，位于这些初始步骤下游的效应器尚未完全确定。目前的实验表征了单次向大鼠侧脑通气孔注射C75后吞噬减少和体重减轻的时间过程，并继续识别特定的进食模式变化和与进食相关的下丘脑神经肽基因表达的变化。C75可依赖地减少食物摄入量和体重剂量。虽然主要影响发生在第一天，但与车辆控制相关的体重减轻持续了好几天。C75不影响全身运动活动。C75在延迟6小时后开始减少摄食。吞噬功能低下的主要原因是在6-12小时内进食次数减少，但对进餐大小没有显著影响，这表明中枢C75降低了开始进餐的动力。在22小时和6小时，当C75开始抑制摄食时，C75可阻止预期的低吞噬诱导的弓状核AgRP基因表达的增加。总体而言，数据表明，导致黑素皮质素信号改变的基因表达变化对于脑室内C75的低吞噬反应是重要的。
3-Carboxy4- alkyl-2-methylenebutyrolactone (C75), an inhibitor of fatty acid synthase and stimulator of carnitine palmitoyltransferase-1, reduces food intake and body weight in rodents when given systemically or centrally. Intracellular molecular mechanisms involving changes in cellular energy status are proposed to initiate the feeding and body weight reductions. However, effectors that lie downstream of these initial steps are not yet fully identified. Present experiments characterize the time courses of hypophagia and weight loss after single injections of C75 into the lateral cerebroventicle in rats and go on to identify specific meal pattern changes and coinciding alterations in gene expression for feeding-related hypothalamic neuropeptides. C75 reduced chow intake and body weight dose dependently. Although the principal effects occurred on the first day, weight losses relative to vehicle control were maintained over multiple days. C75 did not affect generalized locomotor activity. C75 began to reduce feeding after a 6-h delay. The hypophagia was due primarily to decreased meal number during 6-12 h without a significant effect on meal size, suggesting that central C75 reduced the drive to initiate meals. C75 prevented the anticipated hypophagia-induced increases in mRNA for AgRP in the arcuate nucleus at 22 h and at 6 h when C75 begins to suppress feeding. Overall, the data suggest that gene expression changes leading to altered melanocortin signaling are important for the hypophagic response to intracerebroventricular C75.