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

Autor(es)

Pedroso, Amanda P. ^[1] ; Dornellas, Ana P. S. ^[1] ; de Souza, Adriana P. ^[1] ; Pagotto, Josias F. ^[2] ; Oyama, Lila M. ^[1] ; Nascimento, Claudia M. O. ^[1] ; Klawitter, Jelena ^[3] ; Christians, Uwe ^[3] ; Tashima, Alexandre K. ^[2] ; Ribeiro, Eliane Beraldi ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Dept Fisiol, Escola Paulista Med, Rua Botucatu 862, BR-04023062 Sao Paulo, SP - Brazil

^[2] Univ Fed Sao Paulo, Dept Bioquim, Escola Paulista Med, Sao Paulo, SP - Brazil

^[3] Univ Colorado Denver, IC42 Clin Res & Dev, Dept Anesthesiol, Anschutz Med Campus, Aurora, CO - USA

• Tipo de documento: Artigo Científico
• Fonte: EUROPEAN JOURNAL OF NUTRITION; v. 58, n. 8, p. 3059-3068, DEC 2019.
• Citações Web of Science: 1

Resumo

PurposeIntrauterine 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.MethodsWistar 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.ResultsThe 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, alpha -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.ConclusionThe 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. (AU)

• Processo FAPESP: 12/19321-9 - Caracterização proteômica e peptidômica dos venenos de aranhas brasileiras por espectrometria de massas
• Beneficiário: Alexandre Keiji Tashima
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 10/20268-0 - Expressão protéica no hipotálamo e tecido adiposo de ratos machos e fêmeas adultos expostos a desnutrição intrauterina
• Beneficiário: Eliane Beraldi Ribeiro
• Modalidade de apoio: Auxílio à Pesquisa - Regular