| First Author | Qiao L | Year | 2016 |
| Journal | Diabetologia | Volume | 59 |
| Issue | 11 | Pages | 2417-2425 |
| PubMed ID | 27495989 | Mgi Jnum | J:237044 |
| Mgi Id | MGI:5810809 | Doi | 10.1007/s00125-016-4061-x |
| Citation | Qiao L, et al. (2016) Knockout maternal adiponectin increases fetal growth in mice: potential role for trophoblast IGFBP-1. Diabetologia 59(11):2417-25 |
| abstractText | 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 (PPARalpha) 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 PPARalpha 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. |
