Early and persistent up-regulation of hypothalamic orexigenic peptides in rat offspring born to dams fed a high-carbohydrate supplement during gestation

Early and persistent up-regulation of hypothalamic orexigenic peptides in rat offspring born to dams fed a high-carbohydrate supplement during gestation
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DOI:
10.1016/j.brainres.2012.08.021
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发表时间:
2012-10-05
期刊:
影响因子:
2.9
通讯作者:
Mercer, Julian G.
Mercer, Julian G.
中科院分区:
医学3区
文献类型:
--
作者:
Beck, Bernard;Richy, Sebastien;Mercer, Julian G.

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母体在妊娠期摄入的饮食可以深刻地改变下丘脑神经肽的产生和活动,参与喂养和体重调节。在这项研究中,我们开始在大鼠模型中模拟孕妇经常观察到的喂养习惯的改变。饲喂有限制的正常饲粮,并有机会通过高脂肪(HF)或高碳水化合物(HC)饲粮来完成其能量需求。在3周龄(断奶)和20周龄时测定后代的生长和下丘脑喂养肽。断奶时,HC幼崽的体重低于HF幼崽或随意饲喂对照饲粮的对照(Ca)幼崽。HC犬弓形核中神经肽Y (NPY)和AgRP mRNA的表达明显高于Ca和HF犬。到20周龄时,体重差异消失,NPY和AgRP基因表达没有差异,尽管HC大鼠的POMC表达低于HF大鼠。这个年龄HC大鼠室旁核NPY和食欲素肽浓度高于Ca和HF大鼠。在HC大鼠中,NPY和orexin的释放区和合成区之间的肽浓度也有较大的正梯度。HC大鼠早期摄氧肽的上调可能是对低体重的代偿性调节。这种持续过度活跃的摄氧驱动可能对成年期的致肥环境产生有害的代谢影响。(C) 2012 Elsevier B.V.版权所有
Maternal diet ingested during gestation can profoundly alter production and action of hypothalamic neuropeptides involved in feeding and body weight regulation. In this study, we set out to simulate, in a rat model, modifications to feeding habit often observed in pregnant women. Gestating dams were fed a restricted normal diet with the opportunity to complete their energy requirements with either a high-fat (HF) or a high-carbohydrate (HC) diet. Growth and hypothalamic feeding peptides were measured in the offspring at 3 (weaning) and 20 weeks of age. At weaning, body weight was lower in HC pups than in HF pups or control (Ca) pups born to dams fed control diet ad libitum. Expression of neuropeptide Y (NPY) and AgRP mRNA in the arcuate nucleus were increased in HC pups vs Ca and HF pups. By 20 weeks of age, body weight differentials had disappeared, and there was no differences in NPY and AgRP gene expression, although POMC expression was lower in HC rats than in HF rats. NPY and orexin peptide concentrations in the paraventricular nucleus at this age were higher in HC rats than in Ca and HF rats. In HC rats, there was also a greater positive gradient of peptide concentration between the zone of release and the zone of synthesis for NPY and orexin. The early up-regulation of orexigenic peptides in HC rats may be a compensatory adjustment to low body weight. This persisting overactive orexigenic drive might have deleterious metabolic effects in an obesogenic environment at adulthood. (C) 2012 Elsevier B.V. All rights reserved.