Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Placental FTO expression relates to fetal growth

International Journal of Obesity volume 34, pages 1365–1370 (2010)Cite this article

Subjects

Abstract

Objective:

The fat mass and obesity-associated gene (FTO) participates in the control of postnatal weight gain. We assessed whether FTO is expressed in human placenta and whether such expression relates to prenatal weight gain and to the rs9939609 single nucleotide polymorphism (SNP) in FTO.

Design and subjects:

In a birth cohort study, placentas from women (n=147) with an uncomplicated, singleton, term pregnancy were weighed at delivery. Real-time PCR was used to study, in placental tissue, the expression of FTO and of housekeeping genes (TATA box binding protein and succinate dehydrogenase complex, subunit A) and to genotype the rs9939609 SNP in FTO. Weights and lengths of the newborns were measured; circulating insulin and insulin-like growth factor-I (IGF-I) were quantified in cord blood.

Results:

FTO was highly expressed in placenta and was associated with increased fetal weight and length (P<0.001 to P<0.0001). Maternal parity showed an interaction (P<0.001) in the association between placental FTO expression and placental weight. Placental FTO mRNA expression was associated with increased fetal-to-placental weight ratio (P<0.005) in infants from primiparous women, and was associated with increased fetal weight and length and placental weight (P<0.001 to P<0.0001) in infants from nonprimiparous women. These associations were not explained by either cord insulin or IGF-I. Placental FTO expression was unrelated to placental FTO rs9939609 SNP

Conclusion:

FTO is expressed in the human placenta. In a maternal parity-dependent manner, placental FTO may participate either in the control of fetal weight gain or in the partitioning between placental and fetal growth.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Hales CN, Barker DJ . The thrifty phenotype hypothesis. Br Med Bull 2001; 60: 5–20.

    Article  CAS  Google Scholar 

  2. Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 2007; 316: 889–894.

    Article  CAS  Google Scholar 

  3. Dina C, Meyre D, Gallina S, Durand E, Korner A, Jacobson P et al. Variation in FTO contributes to childhood obesity and severe adult obesity. Nat Genet 2007; 39: 724–726.

    Article  CAS  Google Scholar 

  4. Scuteri A, Sanna S, Chen WM, Uda M, Albai G, Strait J et al. Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genet 2007; 3: e115.

    Article  Google Scholar 

  5. Peeters A, Beckers S, Verrijken A, Roevens P, Peeters P, Van Gaal L et al. Variants in the FTO gene are associated with common obesity in the Belgian population. Mol Genet Metab 2008; 93: 481–484.

    Article  CAS  Google Scholar 

  6. Andreasen CH, Stender-Petersen KL, Mogensen MS, Torekov SS, Wegner L, Andersen G et al. Low physical activity accentuates the effect of the FTO rs9939609 polymorphism on body fat accumulation. Diabetes 2008; 57: 95–101.

    Article  CAS  Google Scholar 

  7. Zabena C, Gonzalez-Sanchez JL, Martinez-Larrad MT, Torres-Garcia A, Alvarez-Fernandez-Represa J, Corbaton-Anchuelo A et al. The FTO obesity gene. Genotyping and gene expression analysis in morbidly obese patients. Obes Surg 2009; 19: 87–95.

    Article  Google Scholar 

  8. Stratigopoulos G, Padilla SL, LeDuc CA, Watson E, Hattersley AT, McCarthy MI et al. Regulation of Fto/Ftm gene expression in mice and humans. Am J Physiol Regul Integr Comp Physiol 2008; 294: R1185–R1196.

    Article  CAS  Google Scholar 

  9. Wahlen K, Sjolin E, Hoffstedt J . The common rs9939609 gene variant of the fat mass- and obesity-associated gene FTO is related to fat cell lipolysis. J Lipid Res 2008; 49: 607–611.

    Article  Google Scholar 

  10. Gerken T, Girard CA, Tung YC, Webby CJ, Saudek V, Hewitson KS et al. The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science 2007; 318: 1469–1472.

    Article  CAS  Google Scholar 

  11. Church C, Lee S, Bagg EA, McTaggart JS, Deacon R, Gerken T et al. A mouse model for the metabolic effects of the human fat mass and obesity associated FTO gene. PLoS Genet 2009; 5: e1000599.

    Article  Google Scholar 

  12. Fredriksson R, Hagglund M, Olszewski PK, Stephansson O, Jacobsson JA, Olszewska AM et al. The obesity gene, FTO, is of ancient origin, up-regulated during food deprivation and expressed in neurons of feeding-related nuclei of the brain. Endocrinology 2008; 149: 2062–2071.

    Article  CAS  Google Scholar 

  13. Speakman JR, Rance KA, Johnstone AM . Polymorphisms of the FTO gene are associated with variation in energy intake, but not energy expenditure. Obesity (Silver Spring) 2008; 16: 1961–1965.

    Article  CAS  Google Scholar 

  14. Timpson NJ, Emmett PM, Frayling TM, Rogers I, Hattersley AT, McCarthy MI et al. The fat mass- and obesity-associated locus and dietary intake in children. Am J Clin Nutr 2008; 88: 971–978.

    Article  CAS  Google Scholar 

  15. Wardle J, Carnell S, Haworth CM, Farooqi IS, O’Rahilly S, Plomin R . Obesity associated genetic variation in FTO is associated with diminished satiety. J Clin Endocrinol Metab 2008; 93: 3640–3643.

    Article  CAS  Google Scholar 

  16. Cecil JE, Tavendale R, Watt P, Hetherington MM, Palmer CN . An obesity-associated FTO gene variant and increased energy intake in children. N Engl J Med 2008; 359: 2558–2566.

    Article  CAS  Google Scholar 

  17. den Hoed M, Westerterp-Plantenga MS, Bouwman FG, Mariman EC, Westerterp KR . Postprandial responses in hunger and satiety are associated with the rs9939609 single nucleotide polymorphism in FTO. Am J Clin Nutr 2009; 90: 1426–1432.

    Article  CAS  Google Scholar 

  18. Olszewski PK, Fredriksson R, Olszewska AM, Stephansson O, Alsio J, Radomska KJ et al. Hypothalamic FTO is associated with the regulation of energy intake not feeding reward. BMC Neurosci 2009; 10: 129.

    Article  Google Scholar 

  19. Tanofsky-Kraff M, Han JC, Anandalingam K, Shomaker LB, Columbo KM, Wolkoff LE et al. The FTO gene rs9939609 obesity-risk allele and loss of control over eating. Am J Clin Nutr 2009; 90: 1483–1488.

    Article  CAS  Google Scholar 

  20. Tews D, Fischer-Posovszky P, Wabitsch M . FTO—friend or foe? Horm Metab Res 2010; 42: 75–80.

    Article  CAS  Google Scholar 

  21. Tung YC, Ayuso E, Shan X, Bosch F, O’Rahilly S, Coll AP et al. Hypothalamic-specific manipulation of Fto, the ortholog of the human obesity gene FTO, affects food intake in rats. PLoS One 2010; 5: e8771.

    Article  Google Scholar 

  22. Fischer J, Koch L, Emmerling C, Vierkotten J, Peters T, Bruning JC et al. Inactivation of the Fto gene protects from obesity. Nature 2009; 458: 894–898.

    Article  CAS  Google Scholar 

  23. Hakanen M, Raitakari OT, Lehtimaki T, Peltonen N, Pahkala K, Sillanmaki L et al. FTO genotype is associated with body mass index after the age of seven years but not with energy intake or leisure-time physical activity. J Clin Endocrinol Metab 2009; 94: 1281–1287.

    Article  CAS  Google Scholar 

  24. Jacobsson JA, Danielsson P, Svensson V, Klovins J, Gyllensten U, Marcus C et al. Major gender difference in association of FTO gene variant among severely obese children with obesity and obesity related phenotypes. Biochem Biophys Res Commun 2008; 368: 476–482.

    Article  CAS  Google Scholar 

  25. Lopez-Bermejo A, Petry CJ, Diaz M, Sebastiani G, de Zegher F, Dunger DB et al. The association between the FTO gene and fat mass in humans develops by the postnatal age of two weeks. J Clin Endocrinol Metab 2008; 93: 1501–1505.

    Article  CAS  Google Scholar 

  26. Randhawa R, Cohen P . The role of the insulin-like growth factor system in prenatal growth. Mol Genet Metab 2005; 86: 84–90.

    Article  CAS  Google Scholar 

  27. Lezcano-Carrascosa A, Fernández-García JM, Ferrández-Longás A, López-Siguero JP, Sánchez-González E (eds). Cross-Sectional Study of Growth and Development, 1st edn. Pfizer, S.A: Barcelona, Spain, 2008.

    Google Scholar 

  28. Ong KK, Preece MA, Emmett PM, Ahmed ML, Dunger DB . Size at birth and early childhood growth in relation to maternal smoking, parity and infant breast-feeding: longitudinal birth cohort study and analysis. Pediatr Res 2002; 52: 863–867.

    Article  Google Scholar 

  29. Grunnet LG, Nilsson E, Ling C, Hansen T, Pedersen O, Groop L et al. Regulation and function of FTO mRNA expression in human skeletal muscle and subcutaneous adipose tissue. Diabetes 2009; 58: 2402–2408.

    Article  CAS  Google Scholar 

  30. Clifton IJ, McDonough MA, Ehrismann D, Kershaw NJ, Granatino N, Schofield CJ . Structural studies on 2-oxoglutarate oxygenases and related double-stranded beta-helix fold proteins. J Inorg Biochem 2006; 100: 644–669.

    Article  CAS  Google Scholar 

  31. Sebert SP, Hyatt MA, Chan LL, Yiallourides M, Fainberg HP, Patel N et al. Influence of prenatal nutrition and obesity on tissue specific fat mass and obesity-associated (FTO) gene expression. Reproduction 2010; 139: 265–274.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We are grateful to all families who took part in the study. Supported by Grant No. 07/0404 (to AL-B) from the National Institute of Health Carlos III (Fund for Health Research FIS, Spain). JB is an investigator of the Fund Sara Borrell from the National Institute of Health Carlos III, Spain. FdZ is a clinical investigator of the Fund for Scientific Research (Flanders, Belgium). LI and MD are clinical investigators of CIBERDEM (Center for Network Biomedical Research in Diabetes and Related Metabolic Diseases), from the National Institute of Health Carlos III, Spain. AL-B is an investigator of the Fund for Scientific Research I3 (Ministry of Science and Innovation, Spain).

Author information

Authors and Affiliations

  1. Department of Pediatrics, Dr Josep Trueta Hospital, Girona, Spain

    J Bassols, A Prats-Puig & A López-Bermejo

  2. Girona Institute for Biomedical Research, Girona, Spain

    J Bassols, A Prats-Puig & A López-Bermejo

  3. Department of Pediatrics, Salut Empordà Foundation, Figueres, Spain

    M Vázquez-Ruíz, M-M García-González, R Fàbrega & C Colomer-Virosta

  4. Department of Obstetrics and Gynecology, Salut Empordà Foundation, Figueres, Spain

    M Martínez-Pascual, P Avellí & R Martínez-Martínez

  5. Clinical Laboratory, Salut Empordà Foundation, Figueres, Spain

    P Soriano-Rodríguez

  6. Department of Pediatric Endocrinology, Sant Joan de Déu Children's Hospital, Esplugues, Barcelona, Spain

    M Díaz & L Ibánez

  7. CIBERDEM (Center for Network Biomedical Research in Diabetes and Related Metabolic Diseases), ISCIII, Madrid, Spain

    M Díaz & L Ibánez

  8. Department of Woman and Child, University of Leuven, Leuven, Belgium

    F de Zegher

Authors
  1. J Bassols
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A Prats-Puig
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M Vázquez-Ruíz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M-M García-González
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M Martínez-Pascual
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. P Avellí
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. R Martínez-Martínez
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. R Fàbrega
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. C Colomer-Virosta
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. P Soriano-Rodríguez
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. M Díaz
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. F de Zegher
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. L Ibánez
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. A López-Bermejo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A López-Bermejo.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bassols, J., Prats-Puig, A., Vázquez-Ruíz, M. et al. Placental FTO expression relates to fetal growth. Int J Obes 34, 1365–1370 (2010). https://doi.org/10.1038/ijo.2010.62

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ijo.2010.62

Keywords

This article is cited by

Search

Advanced search

Quick links