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Fructose only in pregnancy provokes hyperinsulinemia, hypoadiponectinemia, and impaired insulin signaling in adult male, but not female, progeny

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Abstract

Purpose

Fructose intake from added sugars correlates with the epidemic rise in metabolic syndrome and cardiovascular diseases. However, consumption of beverages containing fructose is allowed during gestation. Recently, we found that an intake of fructose (10 % wt/vol) throughout gestation produces impaired fetal leptin signaling and hepatic steatosis. Therefore, we have investigated whether fructose intake during pregnancy produces subsequent changes in the progeny, when adult.

Methods

Fed 261-day-old male and female descendants from fructose-fed, control or glucose-fed mothers were used. Plasma was used to analyze glucose, insulin, leptin, and adiponectin. Hepatic expression of proteins related to insulin signaling was determined.

Results

Fructose intake throughout pregnancy did not produce alterations in the body weight of the progeny. Adult male progeny of fructose-fed mothers had elevated levels of insulin without a parallel increase in phosphorylation of protein kinase B. However, they displayed an augmented serine phosphorylation of insulin receptor substrate-2, indicating reduced insulin signal transduction. In agreement, adiponectin levels, which have been positively related to insulin sensitivity, were lower in male descendants from fructose-fed mothers than in the other two groups. Furthermore, mRNA levels for insulin-responsive genes were not affected (phosphoenolpyruvate carboxykinase, glucose-6-phosphatase) or they were decreased (sterol response element-binding protein-1c) in the livers of male progeny from fructose-supplemented rats. On the contrary, adult female rats from fructose-fed mothers did not exhibit any of these disturbances.

Conclusion

Maternal fructose, but not glucose, intake confined to the prenatal stage provokes impaired insulin signal transduction, hyperinsulinemia, and hypoadiponectinemia in adult male, but not female, progeny.

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Acknowledgments

The authors thank Jose M. Garrido for his help in handling the rats and Brian Crilly for his editorial help. This work was supported by grants from the Instituto de Salud Carlos III-Subdirección General de Evaluación y Fomento de la Investigación (PI-09/02192), European Community FEDER funds, SAF2013-42982-R and from the Generalitat of Catalonia (2013SGR0066), as well as the Fundación Universitaria San Pablo-CEU (PC 09/2012). Silvia Rodrigo is a FUSP-CEU fellowship.

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Authors and Affiliations

  1. Facultad de Farmacia, Universidad San Pablo-CEU, Urbanización Montepríncipe, 28668, Boadilla del Monte, Madrid, Spain

    Lourdes Rodríguez, María I. Panadero, Paola Otero, Silvia Rodrigo & Carlos Bocos

  2. Facultad de Farmacia, Universidad de Barcelona, CIBERobn, Barcelona, Spain

    Núria Roglans & Juan C. Laguna

  3. CQS Lab, Madrid, Spain

    Juan J. Álvarez-Millán

Authors
  1. Lourdes Rodríguez
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  2. María I. Panadero
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  3. Núria Roglans
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  4. Paola Otero
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  5. Silvia Rodrigo
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  6. Juan J. Álvarez-Millán
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  7. Juan C. Laguna
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  8. Carlos Bocos
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Correspondence to Carlos Bocos.

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Rodríguez, L., Panadero, M.I., Roglans, N. et al. Fructose only in pregnancy provokes hyperinsulinemia, hypoadiponectinemia, and impaired insulin signaling in adult male, but not female, progeny. Eur J Nutr 55, 665–674 (2016). https://doi.org/10.1007/s00394-015-0886-1

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