Prenatal caffeine ingestion induces transgenerational neuroendocrine metabolic programming alteration in second generation rats
Prenatal caffeine ingestion induces transgenerational neuroendocrine metabolic programming alteration in second generation rats
复制标题
产前摄入咖啡因会诱导第二代大鼠发生跨代神经内分泌代谢编程改变。
DOI：
10.1016/j.taap.2013.11.020
复制
发表时间：
2014-02-01
影响因子：
3.8
通讯作者：
Wang, Hui
中科院分区：
文献类型：
--
作者：
Luo, Hanwen;Deng, Zixin;Wang, Hui
我们的前期研究表明，产前摄入咖啡因可导致第一代宫内生长迟缓（IUGR）成年大鼠代谢综合征易感性增加，糖脂代谢表型改变，其机制可能与子宫内下丘脑-垂体-肾上腺（HPA）轴相关的神经内分泌代谢程序改变有关。本研究旨在探讨这种编程改变在成年第二代（F2）的跨代影响。妊娠Wistar大鼠从妊娠第11天开始给予咖啡因（120 mg/kg.d）直至分娩。F2代根据对照组与咖啡因诱导IUGR大鼠的交配情况，设4组。F2在出生后4个月进行为期两周的冰水游泳刺激，并在应激前后采集血样。结果表明，F2代大部分HPA轴活性和糖脂代谢表型发生了改变。特别是，与对照组相比，咖啡因组在慢性应激后皮质酮水平升高。与应激前相比，部分实验组血糖水平升高，甘油三酯水平降低。此外，总胆固醇增加率增加，但高密度脂蛋白胆固醇增加率下降，在大多数咖啡因组后的压力。这些跨代效应的特点部分与性别和父母的差异。总之，这些结果表明，生殖和发育毒性和神经内分泌代谢编程机制，产前摄入咖啡因在大鼠中具有跨代效应，这可能有助于解释F2中代谢综合征和相关疾病的易感性。(C)2013 Elsevier Inc. All rights reserved.
Our previous studies have demonstrated that prenatal caffeine ingestion induces an increased susceptibility to metabolic syndrome with alterations of glucose and lipid metabolic phenotypes in adult first generation (F1) of intrauterine growth retardation (IUGR) rats, and the underlying mechanism is originated from a hypothalamic-pituitary-adrenal (HPA) axis-associated neuroendocrine metabolic programming alteration in utero. This study aims to investigate the transgenerational effects of this programming alteration in adult second generation (F2). Pregnant Wistar rats were administered with caffeine (120 mg/kg.d) from gestational day 11 until delivery. Four groups in F2 were set according to the cross-mating between control and caffeine-induced IUGR rats. F2 were subjected to a fortnight ice water swimming stimulus on postnatal month 4, and blood samples were collected before and after stress. Results showed that the majority of the activities of HPA axis and phenotypes of glucose and lipid metabolism were altered in F2. Particularly, comparing with the control group, caffeine groups had an enhanced corticosterone levels after chronic stress. Compared with before stress, the serum glucose levels were increased in some groups whereas the triglyceride levels were decreased. Furthermore, total cholesterol gain rates were enhanced but the high-density lipoprotein-cholesterol gain rates were decreased in most caffeine groups after stress. These transgenerational effects were characterized partially with gender and parental differences. Taken together, these results indicate that the reproductive and developmental toxicities and the neuroendocrine metabolic programming mechanism by prenatal caffeine ingestion have transgenerational effects in rats, which may help to explain the susceptibility to metabolic syndrome and associated diseases in F2. (C) 2013 Elsevier Inc. All rights reserved.