Neonatal exposure to oxidants induces later in life a metabolic response associated to a phenotype of energy deficiency in an animal model of total parenteral nutrition.
Failure to protect total parenteral nutrition (TPN) from ambient light exacerbates the generation of peroxides, which affects blood glucose and plasma triacylglyceride (TG) in neonates. Based on the concept that the origin of adult diseases can be traced back to perinatal life, it was hypothesized that neonatal exposure to peroxides may affect energy availability later in life. Three-day-old guinea pigs, fitted with a jugular catheter, were fed regular chow (sham) +/- i.v. 350 microM H2O2 (sham + H2O2) or nourished with light-protected TPN [TPN(-)L, 209 +/- 9 microM peroxides] or light-exposed TPN [TPN(+)L, 365 +/- 15 microM peroxides]. After 4 d, infusions were stopped and animals fed chow. Spontaneous ambulatory movements, fasting blood glucose, glucose tolerance, TG, hepatic activities of glucokinase, phosphofructokinase (key enzymes of glycolysis), and acetyl-CoA carboxylase (key enzymes of lipogenesis) were determined at 12-14 wk and compared by ANOVA (p < 0.05). Relative to sham, the animals from sham + H2O2, TPN(-)L and TPN(+)L groups had lower plasma TG explained for 36% by low phosphofructokinase activity; they had lower glucose tolerance, lower body weight, and lower physical activity. In conclusion, neonatal exposure to oxidant molecules such as peroxides has important consequences later in life on lipid and glucose metabolism leading to a phenotype of energy deficiency.
Kleiber
Niina
N
Department of Pediatrics, CHU Sainte-Justine, University of Montréal, 3175 Chemin de la Côte Ste-Catherine, Montréal, Québec, Canada.
Chessex
Philippe
P
Rouleau
Thérèse
T
Nuyt
Anne-Monique
AM
Perreault
Maude
M
Lavoie
Jean-Claude
JC
D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose / Q000378:metabolism; D016022:Case-Control Studies; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D005941:Glucokinase / Q000378:metabolism; D006168:Guinea Pigs; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D023421:Models, Animal; D009068:Movement / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D010289:Parenteral Nutrition, Total / Q000009:adverse effects*; D010545:Peroxides / Q000009:adverse effects*; D025221:Phosphofructokinases / Q000378:metabolism
D001786:Blood Glucose; D010545:Peroxides; D025221:Phosphofructokinases; D005941:Glucokinase; D000103:Acetyl-CoA Carboxylase