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Diabetologia
Published in: Diabetologia 11/2016

01-11-2016 | Article

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

Authors: Liping Qiao, Jean-Sebastien Wattez, Samuel Lee, Zhuyu Guo, Jerome Schaack, William W. Hay Jr, Matteo Moretto Zita, Mana Parast, Jianhua Shao

Published in: Diabetologia | Issue 11/2016

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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.
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Literature
1.
Ogden CL, Fryar CD, Flegal KM (2015) Prevalence of obesity among adults and youth: United States, 2011–2014. National Center for Health Statistics Data Brief No. 219. National Center for Health Statistics, Hyattsville, MD, USA
2.
3.
Rooney K, Ozanne SE (2011) Maternal over-nutrition and offspring obesity predisposition: targets for preventative interventions. Int J Obes (Lond) 35:883–890CrossRef
4.
5.
Barker DJ, Thornburg KL (2013) The obstetric origins of health for a lifetime. Clin Obstet Gynecol 56:511–519CrossRefPubMed
6.
Dimasuay KG, Boeuf P, Powell TL, Jansson T (2016) Placental responses to changes in the maternal environment determine fetal growth. Front Physiol 7:12CrossRefPubMedPubMedCentral
7.
Randhawa R, Cohen P (2005) The role of the insulin-like growth factor system in prenatal growth. Mol Genet Metab 86:84–90CrossRefPubMed
8.
Constancia M, Hemberger M, Hughes J et al (2002) Placental-specific IGF-II is a major modulator of placental and fetal growth. Nature 417:945–948CrossRefPubMed
9.
Baker J, Liu JP, Robertson EJ, Efstratiadis A (1993) Role of insulin-like growth factors in embryonic and postnatal growth. Cell 75:73–82CrossRefPubMed
10.
Walenkamp MJ, Losekoot M, Wit JM (2013) Molecular IGF-1 and IGF-1 receptor defects: from genetics to clinical management. Endocr Dev 24:128–137CrossRefPubMed
11.
DeChiara TM, Efstratiadis A, Robertson EJ (1990) A growth-deficiency phenotype in heterozygous mice carrying an insulin-like growth factor II gene disrupted by targeting. Nature 345:78–80CrossRefPubMed
12.
Powell-Braxton L, Hollingshead P, Warburton C et al (1993) IGF-I is required for normal embryonic growth in mice. Genes Dev 7:2609–2617CrossRefPubMed
13.
Ben Lagha N, Seurin D, Le Bouc Y et al (2006) Insulin-like growth factor binding protein (IGFBP-1) involvement in intrauterine growth retardation: study on IGFBP-1 overexpressing transgenic mice. Endocrinology 147:4730–4737CrossRefPubMed
14.
Chard T (1994) Insulin-like growth factors and their binding proteins in normal and abnormal human fetal growth. Growth Regul 4:91–100PubMed
15.
16.
Holly JM, Perks CM (2012) Insulin-like growth factor physiology: what we have learned from human studies. Endocrinol Metab Clin N Am 41:249–263
17.
Crossey PA, Pillai CC, Miell JP (2002) Altered placental development and intrauterine growth restriction in IGF binding protein-1 transgenic mice. J Clin Invest 110:411–418CrossRefPubMedPubMedCentral
18.
Gay E, Seurin D, Babajko S, Doublier S, Cazillis M, Binoux M (1997) Liver-specific expression of human insulin-like growth factor binding protein-1 in transgenic mice: repercussions on reproduction, ante-and perinatal mortality and postnatal growth. Endocrinology 138:2937–2947CrossRefPubMed
19.
Rajkumar K, Barron D, Lewitt MS, Murphy LJ (1995) Growth retardation and hyperglycemia in insulin-like growth factor binding protein-1 transgenic mice. Endocrinology 136:4029–4034CrossRefPubMed
20.
Tosh DN, Fu Q, Callaway CW et al (2010) Epigenetics of programmed obesity: alteration in IUGR rat hepatic IGF1 mRNA expression and histone structure in rapid vs. delayed postnatal catch-up growth. Am J Physiol Gastrointest Liver Physiol 299:G1023–G1029CrossRefPubMedPubMedCentral
21.
22.
Jansson N, Nilsfelt A, Gellerstedt M et al (2008) Maternal hormones linking maternal body mass index and dietary intake to birth weight. Am J Clin Nutr 87:1743–1749PubMed
23.
Aye IL, Powell TL, Jansson T (2013) Review: adiponectin--the missing link between maternal adiposity, placental transport and fetal growth? Placenta 34(Suppl):S40–S45CrossRefPubMed
24.
Rosario FJ, Schumacher MA, Jiang J, Kanai Y, Powell TL, Jansson T (2012) Chronic maternal infusion of full-length adiponectin in pregnant mice down-regulates placental amino acid transporter activity and expression and decreases fetal growth. J Physiol 590:1495–1509CrossRefPubMedPubMedCentral
25.
Catalano PM, Hoegh M, Minium J et al (2006) Adiponectin in human pregnancy: implications for regulation of glucose and lipid metabolism. Diabetologia 49:1677–1685CrossRefPubMed
26.
Soheilykhah S, Mohammadi M, Mojibian M et al (2009) Maternal serum adiponectin concentration in gestational diabetes. Gynecol Endocrinol 25:593–596
27.
Chan TF, Yuan SS, Chen HS et al (2004) Correlations between umbilical and maternal serum adiponectin levels and neonatal birthweights. Acta Obstet Gynecol Scand 83:165–169CrossRefPubMed
28.
Nawrocki AR, Rajala MW, Tomas E et al (2006) Mice lacking adiponectin show decreased hepatic insulin sensitivity and reduced responsiveness to peroxisome proliferator-activated receptor gamma agonists. J Biol Chem 281:2654–2660CrossRefPubMed
29.
Qiao L, MacLean PS, Schaack J et al (2005) C/EBPalpha regulates human adiponectin gene transcription through an intronic enhancer. Diabetes 54:1744–1754CrossRefPubMed
30.
Li Y, Moretto-Zita M, Soncin F et al (2013) BMP4-directed trophoblast differentiation of human embryonic stem cells is mediated through a ΔNp63+ cytotrophoblast stem cell state. Development 140:3965–3976CrossRefPubMedPubMedCentral
31.
32.
Qiao L, Zou C, van der Westhuyzen DR, Shao J (2008) Adiponectin reduces plasma triglyceride by increasing VLDL triglyceride catabolism. Diabetes 57:1824–1833CrossRefPubMedPubMedCentral
33.
34.
Qiao L, Yoo HS, Bosco C et al (2014) Adiponectin reduces thermogenesis by inhibiting brown adipose tissue activation in mice. Diabetologia 57:1027–1036CrossRefPubMedPubMedCentral
35.
Milner RD, Hill DJ (1984) Fetal growth control: the role of insulin and related peptides. Clin Endocrinol (Oxf) 21:415–433CrossRef
36.
van Kleffens M, Groffen CA, Dits NF et al (1999) Generation of antisera to mouse insulin-like growth factor binding proteins (IGFBP)-1 to-6: comparison of IGFBP protein and messenger ribonucleic acid localization in the mouse embryo. Endocrinology 140:5944–5952CrossRefPubMed
37.
Carter AM, Nygard K, Mazzuca DM, Han VK (2006) The expression of insulin-like growth factor and insulin-like growth factor binding protein mRNAs in mouse placenta. Placenta 27:278–290CrossRefPubMed
38.
Wang Q, Fujii H, Knipp GT (2002) Expression of PPAR and RXR isoforms in the developing rat and human term placentas. Placenta 23:661–671CrossRefPubMed
39.
Wieser F, Waite L, Depoix C, Taylor RN (2008) PPAR action in human placental development and pregnancy and its complications. PPAR Res 2008:527048CrossRefPubMed
40.
Degenhardt T, Matilainen M, Herzig KH, Dunlop TW, Carlberg C (2006) The insulin-like growth factor-binding protein 1 gene is a primary target of peroxisome proliferator-activated receptors. J Biol Chem 281:39607–39619CrossRefPubMed
41.
van der Meer DL, Degenhardt T, Vaisanen S et al (2010) Profiling of promoter occupancy by PPARalpha in human hepatoma cells via ChIP-chip analysis. Nucleic Acids Res 38:2839–2850CrossRefPubMedPubMedCentral
42.
Aye IL, Gao X, Weintraub ST, Jansson T, Powell TL (2014) Adiponectin inhibits insulin function in primary trophoblasts by PPARalpha-mediated ceramide synthesis. Mol Endocrinol 28:512–524CrossRefPubMedPubMedCentral
43.
Jones HN, Jansson T, Powell TL (2010) Full-length adiponectin attenuates insulin signaling and inhibits insulin-stimulated amino acid transport in human primary trophoblast cells. Diabetes 59:1161–1170CrossRefPubMedPubMedCentral
44.
Aye IL, Rosario FJ, Powell TL, Jansson T (2015) Adiponectin supplementation in pregnant mice prevents the adverse effects of maternal obesity on placental function and fetal growth. Proc Natl Acad Sci U S A 112:12858–12863CrossRefPubMedPubMedCentral
45.
Sivan E, Mazaki-Tovi S, Pariente C et al (2003) Adiponectin in human cord blood: relation to fetal birth weight and gender. J Clin Endocrinol Metab 88:5656–5660CrossRefPubMed
46.
Giudice LC, de Zegher F, Gargosky SE et al (1995) Insulin-like growth factors and their binding proteins in the term and preterm human fetus and neonate with normal and extremes of intrauterine growth. J Clin Endocrinol Metab 80:1548–1555PubMed
47.
Lappas M (2015) Insulin-like growth factor-binding protein 1 and 7 concentrations are lower in obese pregnant women, women with gestational diabetes and their fetuses. J Perinatology 35:32–38
48.
Klauwer D, Blum WF, Hanitsch S, Rascher W, Lee PD, Kiess W (1997) IGF-I, IGF-II, free IGF-I and IGFBP-1,-2 and-3 levels in venous cord blood: relationship to birthweight, length and gestational age in healthy newborns. Acta Paediatr 86:826–833
49.
Hung TY, Lin CC, Hwang YS, Lin SJ, Chou YY, Tsai WH (2008) Relationship between umbilical cord blood insulin-like growth factors and anthropometry in term newborns. Acta paediatr Taiwan 49:19–23
Metadata
Title
Knockout maternal adiponectin increases fetal growth in mice: potential role for trophoblast IGFBP-1
Authors
Liping Qiao
Jean-Sebastien Wattez
Samuel Lee
Zhuyu Guo
Jerome Schaack
William W. Hay Jr
Matteo Moretto Zita
Mana Parast
Jianhua Shao
Publication date
01-11-2016
Publisher
Springer Berlin Heidelberg
Published in
Diabetologia / Issue 11/2016
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-016-4061-x

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