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Open Access 01-12-2019 | Original Contribution

A proteomics–metabolomics approach indicates changes in hypothalamic glutamate–GABA metabolism of adult female rats submitted to intrauterine growth restriction

Authors: Amanda P. Pedroso, Ana P. S. Dornellas, Adriana P. de Souza, Josias F. Pagotto, Lila M. Oyama, Cláudia M. O. Nascimento, Jelena Klawitter, Uwe Christians, Alexandre K. Tashima, Eliane Beraldi Ribeiro

Published in: European Journal of Nutrition | Issue 8/2019

Abstract

Purpose

Intrauterine growth restriction (IUGR) has been shown to induce the programming of metabolic disturbances and obesity, associated with hypothalamic derangements. The present study aimed at investigating the effects of IUGR on the protein and metabolite profiles of the hypothalamus of adult female rats.

Methods

Wistar rats were mated and either had ad libitum access to food (control group) or received only 50% of the control intake (restricted group) during the whole pregnancy. Both groups ate ad libitum throughout lactation. At 4 months of age, the control and restricted female offspring was euthanized for blood and tissues collection. The hypothalami were processed for data independent acquisition mass spectrometry-based proteomics or targeted mass spectrometry-based metabolomics.

Results

The adult females submitted to IUGR showed increased glycemia and body adiposity, with normal body weight and food intake. IUGR modulated significantly 28 hypothalamic proteins and 7 hypothalamic metabolites. The effects of IUGR on hypothalamic proteins and metabolites included downregulation of glutamine synthetase, glutamate decarboxylase, glutamate dehydrogenase, isocitrate dehydrogenase, α-ketoglutarate, and up-regulation of NADH dehydrogenase and phosphoenolpyruvate. Integrated pathway analysis indicated that IUGR affected GABAergic synapse, glutamate metabolism, and TCA cycle, highly interconnected pathways whose derangement has potentially multiple consequences.

Conclusion

The present findings suggested that the effects of IUGR on GABA/glutamate–glutamine cycle may be involved in the programming of obesity and hyperglycemia in female rats.

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Title: A proteomics–metabolomics approach indicates changes in hypothalamic glutamate–GABA metabolism of adult female rats submitted to intrauterine growth restriction
Authors: Amanda P. Pedroso
Ana P. S. Dornellas
Adriana P. de Souza
Josias F. Pagotto
Lila M. Oyama
Cláudia M. O. Nascimento
Jelena Klawitter
Uwe Christians
Alexandre K. Tashima
Eliane Beraldi Ribeiro
Publication date: 01-12-2019
Publisher: Springer Berlin Heidelberg
Published in: European Journal of Nutrition / Issue 8/2019
Print ISSN: 1436-6207
Electronic ISSN: 1436-6215
DOI: https://doi.org/10.1007/s00394-018-1851-6

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