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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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References

Raaijmakers, A, Jacobs, L, Rayyan, M, et al. Catch-up growth in the first two years of life in Extremely Low Birth Weight (ELBW) infants is associated with lower body fat in young adolescence. PLoS One. 2017 Mar 1; 12(3), e0173349.CrossRefGoogle ScholarPubMed
Sipola-Leppänen, M, Vääräsmäki, M, Tikanmäki, M, et al. Cardiometabolic risk factors in young adults who were born preterm. Am J Epidemiol. 2015; 181(11), 861873.CrossRefGoogle ScholarPubMed
South, AM, Nixon, PA, Chappell, MC, et al. Renal function and blood pressure are altered in adolescents born preterm. Pediatr Nephrol. 2019 Jan 1; 34(1), 137144.CrossRefGoogle ScholarPubMed
Kopec, G, Shekhawat, PS, Mhanna, MJ. Prevalence of diabetes and obesity in association with prematurity and growth restriction. Diabetes, Metab Syndr Obes. 2017; 10, 285295.CrossRefGoogle ScholarPubMed
Kerkhof, GF, Willemsen, RH, Leunissen, RWJ, Breukhoven, PE, Hokken-Koelega, ACS. Health profile of young adults born preterm: negative effects of rapid weight gain in early life. J Clin Endocrinol Metab. 2012; 97(12), 44984506.CrossRefGoogle ScholarPubMed
Bassiouny, MR, Almarsafawy, H, Abdel-Hady, H, Nasef, N, Hammad, TA, Aly, H. A randomized controlled trial on parenteral nutrition, oxidative stress, and chronic lung diseases in preterm infants. J Pediatr Gastroenterol Nutr. 2009 Mar; 48(3), 363369.CrossRefGoogle ScholarPubMed
Lavoie, JC, Bélanger, S, Spalinger, M, Chessex, P. Admixture of a multivitamin preparation to parenteral nutrition: the major contributor to in vitro generation of peroxides. Pediatrics. 1997; 99(3), E6.CrossRefGoogle ScholarPubMed
Silvers, KM, Darlow, BA, Winterbourn, CC. Lipid peroxide and hydrogen peroxide formation in parenteral nutrition solutions containing multivitamins. J Parenter Enter Nutr. 2001; 25(1), 1417.CrossRefGoogle ScholarPubMed
Mohamed, I, Elremaly, W, Rouleau, T, Lavoie, JC. Oxygen and parenteral nutrition two main oxidants for extremely preterm infants: “It all adds up”. J Neonatal Perinatal Med. 2015; 8(3), 189197.CrossRefGoogle Scholar
Lavoie, JC, Rouleau, T, Tsopmo, A, Friel, J, Chessex, P. Influence of lung oxidant and antioxidant status on alveolarization: role of light-exposed total parenteral nutrition. Free Radic Biol Med. 2008 Sep 1; 45(5), 572577.CrossRefGoogle ScholarPubMed
Saugstad, OD. Oxidative stress in the newborn - A 30-year perspective. Biol Neonate. 2005; 88(3), 228236.CrossRefGoogle ScholarPubMed
Saugstad, OD. Room air resuscitation-two decades of neonatal research. Early Hum Dev. 2005; 81(1), 111116.CrossRefGoogle ScholarPubMed
Yara, S, Levy, E, Elremaly, W, Rouleau, T, Lavoie, JC. Total parenteral nutrition induces sustained hypomethylation of DNA in newborn guinea pigs. Pediatr Res. 2013; 73(5), 592595.CrossRefGoogle ScholarPubMed
Pradhan, M, Estève, PO, Hang, GC, Samaranayke, M, Kim, G Do, Pradhan, S. CXXC domain of human DNMT1 is essential for enzymatic activity. Biochemistry. 2008; 47(38), 1000010009.CrossRefGoogle ScholarPubMed
Lorente-Pozo, S, Parra-Llorca, A, Núñez-Ramiro, A, et al. The oxygen load supplied during delivery room stabilization of preterm infants modifies the DNA methylation profile. J Pediatr [Internet]. 2018; 202, 7076.e2. Available from: https://doi.org/10.1016/j.jpeds.2018.07.009 CrossRefGoogle ScholarPubMed
Ozsurekci, Y, Aykac, K. Oxidative stress related diseases in newborns. Oxid Med Cell Longev. 2016; 2016, 2768365.CrossRefGoogle ScholarPubMed
Chessex, P, Lavoie, JC, Rouleau, T, et al. Photooxidation of parenteral multivitamins induces hepatic steatosis in a neonatal guinea pig model of intravenous nutrition. Pediatr Res. 2002; 52(6), 958963.CrossRefGoogle Scholar
Maghdessian, R, Côté, F, Rouleau, T, Ouadda, ABD, Levy, É, Lavoie, JC. Ascorbylperoxide contaminating parenteral nutrition perturbs the lipid metabolism in newborn guinea pig. J Pharmacol Exp Ther. 2010; 334(1), 278284.CrossRefGoogle ScholarPubMed
Hyde, MJ, Amusquivar, E, Laws, J, et al. Effects of lipid-supplemented total parenteral nutrition on fatty liver disease in a premature neonatal piglet model. Neonatology. 2008; 93(2), 7786.CrossRefGoogle Scholar
Elremaly, W, Mohamed, I, Rouleau, T, Lavoie, JC. Adding glutathione to parenteral nutrition prevents alveolar loss in newborn Guinea pig. Free Radic Biol Med [Internet]. 2015; 87, 274281. Available from: http://dx.doi.org/10.1016/j.freeradbiomed.2015.06.040 CrossRefGoogle ScholarPubMed
Morin, G, Guiraut, C, Perez Marcogliese, M, Mohamed, I, Lavoie, J-C. Glutathione supplementation of parenteral nutrition prevents oxidative stress and sustains protein synthesis in guinea pig model. Nutrients. 2019; 11(9), 2063.CrossRefGoogle ScholarPubMed
Morrison, JL, Botting, KJ, Darby, JRT, et al. Guinea pig models for translation of the developmental origins of health and disease hypothesis into the clinic. J Physiol. 2018; 596(23), 55355569.CrossRefGoogle ScholarPubMed
Elremaly, W, Mohamed, I, Rouleau, T, Lavoie, JC. Impact of glutathione supplementation of parenteral nutrition on hepatic methionine adenosyltransferase activity. Redox Biol [Internet]. 2016; 8, 1823. Available from: http://dx.doi.org/10.1016/j.redox.2015.12.003 CrossRefGoogle ScholarPubMed
McIntyre, TM, Curthoys, NP. Comparison of the hydrolytic and transfer activities of rat renal gamma-glutamyltranspeptidase. J Biol Chem. 1979; 254(14), 64996504.CrossRefGoogle ScholarPubMed
Turcot, V, Rouleau, T, Tsopmo, A, et al. Long-term impact of an antioxidant-deficient neonatal diet on lipid and glucose metabolism. Free Radic Biol Med [Internet]. 2009; 47(3), 275282. Available from: http://dx.doi.org/10.1016/j.freeradbiomed.2009.04.026 CrossRefGoogle ScholarPubMed
Bradford, MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976; 72(1–2), 248254.CrossRefGoogle ScholarPubMed
Xu, M zhi, Zhang, A zhen, Li, X rong, Xu, W, Shen, L wei. Effects of vanadate on the activities of mice glucokinase and hexokinase. J Zhejiang Univ Sci. 2004; 5(10), 12451248.CrossRefGoogle ScholarPubMed
Hamer, MJ, Dickson, AJ. Developmental changes in hepatic fructose 2,6-bisphosphate content and phosphofructokinase-1 activity in the transition of chicks from embryonic to neonatal nutritional environment. Biochem J. 1987; 245(1), 3539.CrossRefGoogle ScholarPubMed
Karadsheh, NS, Uyeda, K, Oliver, RM. Studies on structure of human erythrocyte phosphofructokinase. J Biol Chem. 1977; 252(10), 35153524.CrossRefGoogle ScholarPubMed
Kudo, N, Barr, AJ, Barr, RL, Desai, S, Lopaschuk, GD. High rates of fatty acid oxidation during reperfusion of ischemic hearts are associated with a decrease in malonyl-CoA levels due to an increase in 5’-AMP-activated protein kinase inhibition of acetyl-CoA carboxylase. J Biol Chem. 1995; 270(29), 1751317520.CrossRefGoogle Scholar
Laemmli, UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970; 227(5259), 680685.CrossRefGoogle ScholarPubMed
Blanchard, CZ, Waldrop, GL. Overexpression and kinetic characterization of the carboxyltransferase component of acetyl-CoA carboxylase. J Biol Chem. 1998; 273(30), 1914019145.CrossRefGoogle ScholarPubMed
Rao, RK, Clayton, LW. Regulation of protein phosphatase 2A by hydrogen peroxide and glutathionylation. Biochem Biophys Res Commun. 2002; 293(1), 610616.CrossRefGoogle ScholarPubMed
Kleiber, N, Chessex, P, Rouleau, T, Nuyt, AM, Perreault, M, Lavoie, JC. 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. Pediatr Res. 2010; 68(3), 188192.CrossRefGoogle Scholar
Tippett, PS, Neet, KE. Interconversions between different sulfhydryl-related kinetic states in glucokinase. Arch Biochem Biophys [Internet]. 1983 Apr 1 [cited 2019 Nov 22]; 222(1), 285298. Available from: http://www.ncbi.nlm.nih.gov/pubmed/6838225 CrossRefGoogle ScholarPubMed
Tiedge, M, Richter, T, Lenzen, S. Importance of cysteine residues for the stability and catalytic activity of human pancreatic beta cell glucokinase. Arch Biochem Biophys. 2000; 375(2), 251260.CrossRefGoogle ScholarPubMed
Winterbourn, CC. The biological chemistry of hydrogen peroxide [Internet]. 1st ed. Vol. 528, Methods in Enzymology. Elsevier Inc., 2013; pp. 325. Available from http://dx.doi.org/10.1016/B978-0-12-405881-1.00001-X Google ScholarPubMed
Gilbert, HF. Biological disulfides: the third messenger? Modulation of phosphofructokinase activity by thiol/disulfide exchange. J Biol Chem [Internet]. 1982 Oct 25 [cited 2019 Nov 22]; 257(20), 1208612091. Available from: http://www.ncbi.nlm.nih.gov/pubmed/6214556 CrossRefGoogle ScholarPubMed
Brigelius, R, Muckel, C, Akerboom, TPM, Sies, H. Identification and quantitation of glutathione in hepatic protein mixed disulfides and its relationship to glutathione disulfide. Biochem Pharmacol. 1983 Sep 1; 32(17), 25292534.CrossRefGoogle ScholarPubMed
Knafo, L, Chessex, P, Rouleau, T, Lavoie, JC. Association between hydrogen peroxide-dependent byproducts of ascorbic acid and increased hepatic acetyl-CoA carboxylase activity. Clin Chem. 2005; 51(8), 14621471.CrossRefGoogle ScholarPubMed
O’Doherty, RM, Lehman, DL, Telemaque-Potts, S, Newgard, CB. Metabolic impact of glucokinase overexpression in liver: lowering of blood glucose in fed rats is accompanied by hyperlipidemia. Diabetes [Internet]. 1999 Oct 1 [cited 2020 Feb 28]; 48(10), 20222027. Available from: http://diabetes.diabetesjournals.org/cgi/doi/10.2337/diabetes.48.10.2022 CrossRefGoogle ScholarPubMed
Lavoie, JC, Chessex, P, Rouleau, T, Migneault, D, Comte, B. Light-induced byproducts of Vitamin C in multivitamin solutions. Clin Chem. 2004; 50(1), 135140.CrossRefGoogle ScholarPubMed
Lavoie, JC, Chessex, P, Rouleau, T, Tsopmo, A, Friel, J. Shielding parenteral multivitamins from light increases vitamin A and E concentration in lung of newborn guinea pigs. Clin Nutr. 2007; 26(3), 341347.CrossRefGoogle Scholar
Blaschke, K, Ebata, KT, Karimi, MM, et al. Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells. Nature. 2013; 500(7461), 222226.CrossRefGoogle Scholar
Yin, R, Mao, SQ, Zhao, B, et al. Ascorbic acid enhances tet-mediated 5-methylcytosine oxidation and promotes DNA demethylation in mammals. J Am Chem Soc. 2013; 135(28), 1039610403.CrossRefGoogle ScholarPubMed
Nau, PN, Van Natta, T, Ralphe, JC, et al. Metabolic adaptation of the fetal and postnatal ovine heart: regulatory role of hypoxia-inducible factors and nuclear respiratory Factor-1. Pediatr Res [Internet]. 2002 Aug [cited 2020 Feb 28]; 52(2), 269278. Available from: http://www.nature.com/doifinder/10.1203/00006450-200208000-00021 CrossRefGoogle ScholarPubMed
Duee, PH, Pegorier, JP, El Manoubi, L. Hepatic triglyceride hydrolysis and development of ketogenesis in rabbits. Am J Physiol - Endocrinol Metab. 1985; 12(5), E478E484.CrossRefGoogle Scholar
Bohmer, T, Havel, RJ, Long, JA. Physiological fatty liver and hyperlipemia in the fetal guinea pig: chemical and ultrastructural characterization. J Lipid Res [Internet]. 1972 May [cited 2020 Feb 28]; 13(3), 371382. Available from: http://www.ncbi.nlm.nih.gov/pubmed/4337157 CrossRefGoogle ScholarPubMed
Bohmer, T, Havel, RJ. Genesis of fatty liver and hyperlipemia in the fetal guinea pig. J Lipid Res [Internet]. 1975 Nov [cited 2020 Feb 28]; 16(6), 454460. Available from: http://www.ncbi.nlm.nih.gov/pubmed/1194788 CrossRefGoogle ScholarPubMed
Logothetopoulos, J, Ridout, JH, Lucas, CC. Fatty livers in fetal and newborn rabbits. Can J Physiol Pharmacol. 1966; 44(1), 173175.CrossRefGoogle ScholarPubMed
Chesta, J, Srai, SKS, Burroughs, AK, Scheuer, PJ, Epstein, O. Copper overload in the developing guinea pig liver: a histological, histochemical and biochemical study. Liver. 1989; 9(4), 198204.CrossRefGoogle ScholarPubMed
Du Bois, AM. The embryonic liver. In The Liver [Internet]. Elsevier. 1963; pp. 139. Available from: https://linkinghub.elsevier.com/retrieve/pii/B9781483228242500078 Google Scholar
Lu, CJH, Redmond, D, Baggs, RB, Schecter, A, Gasiewicz, TA. Growth and hepatic composition in the guinea pig after long-term parenteral hyperalimentation. Am J Physiol - Regul Integr Comp Physiol. 1986; 251(2), R388R397.CrossRefGoogle ScholarPubMed
Ahmad, I, Nemet, D, Eliakim, A, et al. Body composition and its components in preterm and term newborns: a cross-sectional, multimodal investigation. Am J Hum Biol [Internet]. 2010 Jan; 22(1), 6975. Available from: http://doi.wiley.com/10.1002/ajhb.20955 CrossRefGoogle ScholarPubMed
Nuyt, AM, Lavoie, JC, Mohamed, I, Paquette, K, Luu, TM. Adult consequences of extremely preterm birth: cardiovascular and metabolic diseases risk factors, mechanisms, and prevention avenues. Clin Perinatol. 2017; 44(2), 315332.CrossRefGoogle ScholarPubMed
Helbock, HJ, Motchnik, PA, Ames, BN. Toxic hydroperoxides in intravenous lipid emulsions used in preterm infants. Pediatrics. 1993; 91(1 I), 8387.Google ScholarPubMed
Rosa, MJ, Lee, AG, Wright, RJ. Evidence establishing a link between prenatal and early-life stress and asthma development. Curr Opin Allergy Clin Immunol. 2018; 18(2), 148158.CrossRefGoogle ScholarPubMed
Metrustry, SJ, Karhunen, V, Edwards, MH, et al. Metabolomic signatures of low birthweight: pathways to insulin resistance and oxidative stress. Gardner DS, editor. PLoS One [Internet]. 2018 Mar 22 [cited 2020 Feb 28]; 13(3), e0194316. Available from: https://dx.plos.org/10.1371/journal.pone.0194316 CrossRefGoogle ScholarPubMed
Lavoie, JC, Tremblay, A. Sex-specificity of oxidative stress in newborns leading to a personalized antioxidant nutritive strategy. Antioxidants. 2018; 7(4), 111.CrossRefGoogle ScholarPubMed
Lavoie, JC, Chessex, P. Gender and maturation affect glutathione status in human neonatal tissues. Free Radic Biol Med. 1997; 23(4), 648657.CrossRefGoogle ScholarPubMed