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Neonatal parenteral nutrition affects the metabolic flow of glucose in newborn and adult male Hartley guinea pigs’ liver

Published online by Cambridge University Press:  03 August 2020

Vitor Teixeira
Affiliation:
Department of Nutrition, Université de Montréal, 2405 Chemin de la Côte-Sainte-Catherine, Montréal, QCH3T 1A8, Canada
Clémence Guiraut
Affiliation:
Department of Nutrition, Université de Montréal, 2405 Chemin de la Côte-Sainte-Catherine, Montréal, QCH3T 1A8, Canada
Ibrahim Mohamed
Affiliation:
Department of Pediatrics-Neonatology, CHU Sainte-Justine, Université de Montréal, 3175 Chemin de la Côte-Sainte-Catherine, Montréal, QCH3T 1C5, Canada
Jean-Claude Lavoie*
Affiliation:
Department of Nutrition, Université de Montréal, 2405 Chemin de la Côte-Sainte-Catherine, Montréal, QCH3T 1A8, Canada Department of Pediatrics-Neonatology, CHU Sainte-Justine, Université de Montréal, 3175 Chemin de la Côte-Sainte-Catherine, Montréal, QCH3T 1C5, Canada
*
Address for correspondence: Jean-Claude Lavoie, PhD, Research Centre, CHU Sainte-Justine, 3175 Chemin de la Côte Ste-Catherine, Montreal, QC, H3T 1C5, Canada. Email: jean-claude.lavoie@umontreal.ca

Abstract

Extremely premature birth is associated with a permanent disruption of energy metabolism. The underlying mechanisms are poorly understood. The oxidative stress induced by parenteral nutrition (PN) during the first week of life is suspected to reprogram energy metabolism in the liver. Full-term male Hartley guinea pigs (to isolate PN from prematurity) receiving PN enriched or not with glutathione (to isolate PN effects from PN-induced oxidative stress effects) or an Oral Nutrition (ON) during the first week of life were used. At 1 week (neonatal) and 16 weeks (adult), measurements of liver glutathione (GSH and GSSG) and activities of three key enzymes of energy metabolism (glucokinase (GCK), phosphofructokinase (PFK), and acetyl-CoA carboxylase (ACC)) were performed. Differences between groups were reported if p ≤ 0.05 (Analysis of Variance). At 1 week, compared to ON, PN induced higher GSSG (oxidative stress), higher GCK activity, and lower PFK and ACC activity, the glutathione supplement prevented all PN effects. At 16 weeks, early PN induced lower GSSG (reductive stress) and lower GCK activity, which was prevented by added glutathione, and higher ACC activity independent of glutathione supplement. ACC was negatively associated (r2 = 0.33) with GSSG. Increased nicotinamide adenine dinucleotide phosphate levels confirmed the glucose-6-phosphate accumulation at 1 week, whereas our protocol failed to document lipid accumulation at 16 weeks. In adult male guinea pigs, neonatal exposure to PN affected glutathione metabolism leading to reductive stress (lower GSSG) and an altered metabolic flow of glucose. Partial prevention with glutathione supplementation suggests that, in addition to peroxides, other factors of PN are involved.

Type
Original Article
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2020

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