Prenatal nicotine exposure-induced intrauterine programming alteration increases the susceptibility of high-fat diet-induced non-alcoholic simple fatty liver in female adult offspring rats
Prenatal nicotine exposure-induced intrauterine programming alteration increases the susceptibility of high-fat diet-induced non-alcoholic simple fatty liver in female adult offspring rats
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产前尼古丁暴露引起的宫内编程改变增加了雌性成年子代大鼠对高脂饮食引起的非酒精性单纯性脂肪肝的易感性
DOI：
10.1039/c4tx00092g
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Xu D;Bai J;Zhang L;Shen L;Wang LL;Liu ZF;Xia LP;Wang H
以往的研究表明，胎儿宫内发育迟缓(IUGR)胎儿对成人代谢综合征(MS)有较高的易感性。非酒精性单纯性脂肪肝(NAFL)被认为是MS的肝脏表现。在本研究中，我们评估了孕期尼古丁暴露诱导的成年雌性IUGR子代大鼠NAFL的易感性，并进一步探讨了这一现象的潜在宫内编程机制。用尼古丁(2 mg kg−1d−1)建立胎鼠宫内发育迟缓模型，取正常饲料和高脂饲料喂养的雌性胎儿和成年雌性子代的肝组织。尼古丁暴露组的雌性成年后代在高脂肪饮食下表现出较低的出生体重和出生后追赶生长，以及严重的NAFL。此外，随着血清甘油三酯水平的升高，参与肝脏胰岛素样生长因子1(IGF1)途径、糖异生和脂肪合成的基因表达增加，脂肪输出的基因表达减少。尼古丁暴露组的女性胎儿表现出肝脏IGF1途径下调，糖异生、脂肪合成增加和脂肪输出减少的模式也与成年胎儿相似。本研究证实了孕期尼古丁暴露增加雌性子代大鼠对高脂饮食诱导的NAFL易感性的宫内起源，这很可能是由两个宫内编程调节的。即第一个糖皮质激素-IGF1轴规划诱导出生后追赶生长，加重糖脂代谢紊乱，导致成人NAFL易感性增加；而第二个肝脏糖脂代谢规划促进肝脏脂肪生成，减少脂质氧化和输出，促进NAFL。
Previous studies have indicated that the intrauterine growth retardation (IUGR) fetus is faced with a high susceptibility to adult metabolic syndrome (MS). Non-alcoholic simple fatty liver (NAFL) is considered to be the hepatic manifestation of MS. In the present study, we evaluated the susceptibility of high-fat diet-induced NAFL in female adult IUGR offspring rats, induced by prenatal nicotine exposure, and we further explored the underlying intrauterine programming mechanism for this phenomenon. The IUGR rat model was established by prenatal exposure to nicotine (2 mg kg−1 d−1), the liver tissues from female fetuses and female adult offspring fed with normal or high-fat diets were collected. The female adult offspring in the nicotine-exposed group showed low birth weights and postnatal catch-up growth, as well as severe NAFL under high-fat diets. Moreover, increased gene expression involved in the hepatic insulin-like growth factor 1 (IGF1) pathway, gluconeogenesis and lipid synthesis, and decreased gene expression of lipid output accompanied with elevated serum triglyceride levels, was observed. The female fetuses in the nicotine-exposed group showed down-regulated hepatic IGF1 pathways, and also exhibited similar patterns of increased gluconeogenesis, lipid synthesis and decreased lipid output to those in the adults. The present study demonstrates the intrauterine origin of increased susceptibility to high-fat diet-induced NAFL in female offspring rats by prenatal nicotine exposure, which is most likely mediated by “two intrauterine programming”. That is, the first glucocorticoid-IGF1 axis programming induces postnatal catch-up growth, aggravates glucose and lipid metabolic disorders, and leads to an increased susceptibility to adult NAFL, while the second hepatic glucose and lipid metabolic programming enhances hepatic lipogenesis and reduces lipid oxidation and output, promoting NAFL.
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影响因子：
10.9
作者：
Pinney, Sara E.;Simmons, Rebecca A.
通讯作者：
Simmons, Rebecca A.
影响因子：
3.8
作者：
Wang T;Chen M;Liu L;Cheng H;Yan YE;Feng YH;Wang H
通讯作者：
Wang H
DOI：
10.1210/jcem.87.6.8673
发表时间：
2002
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
--
作者：
N. Arends;L. Johnston;A. Hokken-Koelega;C. Van Duijn;M. D. de Ridder;M. Savage;A. Clark
通讯作者：
N. Arends;L. Johnston;A. Hokken-Koelega;C. Van Duijn;M. D. de Ridder;M. Savage;A. Clark
影响因子：
0.7
作者：
G. Farrell;C. Larter
通讯作者：
G. Farrell;C. Larter
影响因子：
7.7
作者：
Li Zhang;Dan Xu;Ben-jian Zhang;Yan-song Liu;Fenglong Chu;Yuming Guo;Jun Gong;Xun Zheng
通讯作者：
Li Zhang;Dan Xu;Ben-jian Zhang;Yan-song Liu;Fenglong Chu;Yuming Guo;Jun Gong;Xun Zheng