Altered Bioenergetic Profile in Umbilical Cord and Amniotic Mesenchymal Stem Cells from Newborns of Obese Women

Laura Iaffaldano, Carmela Nardelli, Francesca D'Alessio, Valeria D'Argenio, Marcella Nunziato, Lucia Mauriello, Claudio Procaccini, Giuseppe Maria Maruotti, Pasquale Martinelli, Giuseppe Matarese, Lucio Pastore, Luigi Del Vecchio, Giuseppe Labruna, Lucia Sacchetti

Research output: Contribution to journalArticle

Abstract

Nutritional imbalance and metabolic alterations associated with maternal obesity during pregnancy predispose offspring to obesity and/or to type 2 diabetes, but the mechanisms underlying these effects are still obscure. In this context, we evaluated whether the two main energy-producing pathways (glycolysis and mitochondrial oxidative phosphorylation) are impaired in obesity during pregnancy thus contributing to metabolic intrauterine alterations. Specifically, we studied metabolic abnormalities in the intrauterine life of newborns using stem cells isolated from amnion and umbilical cord (hA- and hUC-MSCs). We isolated, at delivery, neonatal hUC-MSCs from 13 obese (Ob) and 10 normal weight control (Co) women (prepregnancy body mass index >30 and <25 kg/m2, respectively) and hA-MSCs from a subgroup of 3 Ob and 3 Co women. The hUC-MSC immunophenotype was characterized by flow cytometry. The extracellular acidification rate and oxygen consumption rate, which are indicators of glycolysis and mitochondrial respiration, respectively, were measured using the Seahorse XFe96 analyzer. Basal glycolysis (Co: 27.5 ± 2.9; Ob: 21.3 ± 2.3 mpH/min) and glycolytic capacity (Co: 65.3 ± 1.2; Ob: 55.0 ± 0.3 mpH/min) were significantly lower in Ob-hUC-MSCs versus Co-hUC-MSCs (P < 0.05 and P < 0.0001, respectively). Mitochondrial basal respiration (Co: 46.9 ± 0.7; Ob: 32.6 ± 0.8 pmol/min), ATP-linked respiration (Co: 29.3 ± 1.9; Ob: 20.1 ± 0.3 pmol/min), and maximal respiration (Co: 75.2 ± 5.3; Ob: 50.5 ± 4.1 pmol/min) were significantly (P < 0.0001) lower in Ob-hUC-MSCs versus Co-hUC-MSCs. Similarly, bioenergetic profiles of the subgroup of Ob-hA-MSCs differed from those of Co-hA-MSCs. These results demonstrate that the bioenergetic performance of Ob-h-MSCs is lower in basal conditions and in conditions of increased energy demand compared with Co-h-MSCs. In conclusion, we describe a new mechanism whereby obesity alters intrauterine metabolism. This process could concur to predispose offspring to metabolic diseases in adult life.

Original languageEnglish
Pages (from-to)199-206
Number of pages8
JournalStem Cells and Development
Volume27
Issue number3
DOIs
Publication statusE-pub ahead of print - Dec 5 2017

Keywords

  • amniotic stem cells
  • MSC
  • placenta

ASJC Scopus subject areas

  • Hematology
  • Developmental Biology
  • Cell Biology

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    Iaffaldano, L., Nardelli, C., D'Alessio, F., D'Argenio, V., Nunziato, M., Mauriello, L., Procaccini, C., Maruotti, G. M., Martinelli, P., Matarese, G., Pastore, L., Del Vecchio, L., Labruna, G., & Sacchetti, L. (2017). Altered Bioenergetic Profile in Umbilical Cord and Amniotic Mesenchymal Stem Cells from Newborns of Obese Women. Stem Cells and Development, 27(3), 199-206. https://doi.org/10.1089/scd.2017.0198