Diabetologia

, Volume 59, Issue 11, pp 2417–2425

Knockout maternal adiponectin increases fetal growth in mice: potential role for trophoblast IGFBP-1

  • Liping Qiao
  • Jean-Sebastien Wattez
  • Samuel Lee
  • Zhuyu Guo
  • Jerome Schaack
  • William W. HayJr
  • Matteo Moretto Zita
  • Mana Parast
  • Jianhua Shao
Article

DOI: 10.1007/s00125-016-4061-x

Cite this article as:
Qiao, L., Wattez, JS., Lee, S. et al. Diabetologia (2016) 59: 2417. doi:10.1007/s00125-016-4061-x

Abstract

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 α (PPARα) 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 PPARα 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.

Keywords

Adiponectin Fetus Growth IGF-binding protein Placenta 

Abbreviations

Ad-gfp

Adenoviral vector encoding green fluorescent protein

Ad-Adipoq

Adenoviral vector encoding adiponectin

E

Embryonic day

Fakd

Fetuses from Adipoq−/− dams

Fwtd

Fetuses from wild-type dams

GAPDH

Glyceraldehyde 3-phosphate dehydrogenase

GFP

Green fluorescent protein

IGFBP-1

IGF-binding protein 1

PPARα

Peroxisome proliferator-activated receptor α

qPCR

Quantitative real-time PCR

RT

Room temperature

TG

Triacylglycerol

WT

Wild-type

Supplementary material

125_2016_4061_MOESM1_ESM.pdf (1.1 mb)
ESM(PDF 1142 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Liping Qiao
    • 1
  • Jean-Sebastien Wattez
    • 1
  • Samuel Lee
    • 1
  • Zhuyu Guo
    • 1
  • Jerome Schaack
    • 2
  • William W. HayJr
    • 3
  • Matteo Moretto Zita
    • 4
  • Mana Parast
    • 4
  • Jianhua Shao
    • 1
  1. 1.Department of PediatricsUniversity of California San DiegoLa JollaUSA
  2. 2.Department of MicrobiologyUniversity of Colorado at Denver and Anschutz Medical CenterAuroraUSA
  3. 3.Department of PediatricsUniversity of Colorado School of MedicineAuroraUSA
  4. 4.Department of PathologyUniversity of California San DiegoLa JollaUSA

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