Leptin and Ob-Rb receptor isoform in the human digestive tract during fetal development

Leptin and Ob-Rb receptor isoform in the human digestive tract during fetal development
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DOI:
10.1210/jc.2005-1498
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发表时间:
2005-11-01
影响因子:
5.8
通讯作者:
Lehy, T
Lehy, T
中科院分区:
医学2区
文献类型:
--
作者:
Aparicio, T;Kermorgant, S;Lehy, T

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背景:瘦素,部分由胃产生,是一种参与能量平衡和调节食物摄入的激素。目的:研究人消化道组织中Ob-Rb和胃组织中瘦素的时空分布规律,探讨Ob-Rb和瘦素在胃组织中的分布规律。设计:采用RTPCR、免疫组化、免疫组织化学、免疫组织化学等方法,和Western blot结果:在妊娠7 ~ 9周,所有的羊水组织均表达Ob-Rb(mRNA和/或蛋白)。瘦素蛋白出现在8周的胃粘膜,而瘦素mRNA检测到约11周。羊水中的瘦素水平显着高于在第二个三个月。总体而言,OB-Rb免疫反应性较高,在年轻的胎儿,在此期间相应的形成的胃芽和原始肠隐窝和上皮细胞类型的分化开始,比在最古老的。与对照组相比,添加到10- 12周龄胎儿胃肠道外植体培养基中的瘦素似乎会影响DNA合成,表明瘦素受体功能正在发育。当胎儿开始吞咽时,瘦素在羊水中的强表达,然后在胃粘膜中的强表达,以及粘膜中Ob-Rb的早期存在,表明瘦素的可能作用,在人消化道的发育过程(生长和/或成熟)中,在腔内和旁分泌途径中发挥作用。
Context: Leptin, partially produced by the stomach, is a hormone involved in energy balance and regulation of food intake. It also regulates some digestive functions through its functional receptor Ob-Rb expressed by gastrointestinal epithelial cells.Objective: The objective of the study was to investigate the temporal and spatial appearance of Ob-Rb in the human digestive tract and leptin in the stomach.Design: The esophagus, stomach, and intestine samples of 7- to 24-wk-old human fetuses and adult mucosae were studied by RTPCR, immunohistochemistry, and Western blot. Leptin was measured by RIA in amniotic fluids at 16-33 wk gestation.Results: All mucosae expressed Ob-Rb ( mRNA and/or protein) between 7 and 9 wk gestation. Leptin protein appeared by 8 wk in the gastric mucosa, whereas leptin mRNA was detected around 11 wk. Leptin levels in amniotic fluids were significantly higher during the second than during the third trimester. Overall, Ob-Rb immunoreactivity was higher in young fetuses, during the period corresponding to the formation of gastric buds and primitive intestinal crypts and the beginning of differentiation of epithelial cell types, than in the oldest. Leptin added to culture medium of gastrointestinal explants from 10- to 12-wk-old fetuses appeared to affect DNA synthesis as compared with controls, indicating that leptin receptor functionality was developing.Conclusions: The strong expression of leptin, in amniotic fluid when fetuses begin swallowing then in the gastric mucosa, and the early presence of Ob-Rb in mucosae suggest a possible role for leptin, exerted endoluminally and in a paracrine pathway, in the developmental process ( growth and/or maturation) of the human digestive tract.