期刊
DIABETOLOGIA
卷 59, 期 11, 页码 2417-2425出版社
SPRINGER
DOI: 10.1007/s00125-016-4061-x
关键词
Adiponectin; Fetus; Growth; IGF-binding protein; Placenta
资金
- National Institute of Health [HD069634, DK095132]
- American Diabetes Association [1-16-IBS-272]
Aims/hypothesis The main objective of this study was to investigate whether maternal adiponectin regulates fetal growth through the endocrine system in the fetal compartment. Methods Adiponectin knockout (Adipoq(-/-)) mice and in vivo adenovirus-mediated reconstitution were used to study the regulatory effect of maternal adiponectin on fetal growth. Primary human trophoblast cells were treated with adiponectin and a specific peroxisome proliferator-activated receptor alpha (PPAR alpha) agonist or antagonist to study the underlying mechanism through which adiponectin regulates fetal growth. Results The body weight of fetuses from Adipoq(-/-) dams was significantly greater than that of wild-type dams at both embryonic day (E) 14.5 and E18.5. Adenoviral vector-mediated maternal adiponectin reconstitution attenuated the increased fetal body weight induced by maternal adiponectin deficiency. Significantly increased blood glucose, triacylglycerol and NEFA levels were observed in Adipoq(-/-) dams, suggesting that nutrient supply contributes to maternal adiponectin-regulated fetal growth. Although fetal blood IGF-1 concentrations were comparable in fetuses from Adipoq(-/-) and wild-type dams, remarkably low levels of IGF-binding protein 1 (IGFBP-1) were observed in the serum of fetuses from Adipoq(-/-) dams. IGFBP-1 was identified in the trophoblast cells of human and mouse placentas. Maternal fasting robustly increased IGFBP-1 levels in mouse placentas, while reducing fetal weight. Significantly low IGFBP-1 levels were found in placentas of Adipoq(-/-) dams. Adiponectin treatment increased IGFBP-1 levels in primary cultured human trophoblast cells, while the PPAR alpha antagonist, MK886, abolished this stimulatory effect. Conclusions/interpretation These results indicate that, in addition to nutrient supply, maternal adiponectin inhibits fetal growth by increasing IGFBP-1 expression in trophoblast cells.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据