Programmed alterations in hypothalamic neuronal orexigenic responses to ghrelin following gestational nutrient restriction
Programmed alterations in hypothalamic neuronal orexigenic responses to ghrelin following gestational nutrient restriction
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DOI：
10.1177/1933719108316982
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发表时间：
2008-09-01
影响因子：
2.9
通讯作者：
Ross, Michael G.
中科院分区：
文献类型：
--
作者：
Jia, Yousheng;Nguyen, Tri;Ross, Michael G.
宫内生长受限（IUGR）的后代表现出食欲增加和成年肥胖的倾向。虽然新生儿追赶性生长的速度可能决定成人肥胖的编程，但对食欲途径被修改的机制知之甚少。Ghrelin是一种促食欲肽，作用于下丘脑弓状核（ARC）和腹内侧核（VMH）。为了检查IUGR的潜在编程效应，在先前在怀孕期间（FR/AdLib [随意]）以及怀孕和哺乳期间（FR/FR）受到母体食物限制（FR）的成年后代的脑切片中研究了ghrelin对ARC和VMH神经元的作用。与FR/AdLib和对照后代相比，FR/FR后代在ARC和VMH中表现出基线神经元放电频率增加。FR/AdLib幼鼠表现出贪食和肥胖，ghrelin兴奋更多，抑制更少的ARC神经元相比，无论是FR/FR或控制。这些结果提供了证据的编程食欲/食欲的机制取决于营养水平在怀孕期间和新生儿时期。
Intrauterine growth restricted (IUGR) offspring exhibit increased appetite and a propensity to adult obesity. Although the rate of newborn catch-up growth may determine the programming of adult obesity, there is little understanding of mechanisms by which orexigenic pathways are modified. Ghrelin is an orexigenic peptide that acts in the hypothalamic arcuate (ARC) and ventromedial (VMH) nuclei. To examine potential programming effects of IUGR, ghrelin's actions on ARC and VMH neurons were studied in brain slices of adult offspring previously subjected to maternal food restriction (FR) during pregnancy (FR/AdLib [ad libitum]) and both pregnancy and lactation (FR/FR). FR/FR offspring demonstrated increased baseline neuronal firing frequency in both ARC and VMH when compared with both FR/AdLib and control offspring. Among FR/AdLib pups that exhibit hyperphagia and obesity, ghrelin excited more and inhibited fewer ARC neurons when compared with either FR/FR or controls. These results provide evidence of programming of orexigenic/anorexigenic mechanisms depending on the nutrient levels during pregnancy and newborn peroids.