Free Access
Neonatology 2012;101:217–224
(DOI:10.1159/000331772)

Postnatal Rosiglitazone Administration to Neonatal Rat Pups Does Not Alter the Young Adult Metabolic Phenotype

Truong N.C. · Abbasi A. · Sakurai R. · Lee W.N.P. · Torday J.S. · Rehan V.K.
Department of Pediatrics, David Geffen School of Medicine, University of California at Los Angeles, Torrance, Calif., USA
email Corresponding Author


 goto top of outline Key Words

  • Rosiglitazone
  • Lung development
  • Peroxisome proliferator-activated receptor-γ
  • Fetal programming

 goto top of outline Abstract

Background: Rosiglitazone (RGZ), a peroxisome proliferator-activated receptor-γ (PPARγ) agonist, significantly enhances lung maturation without affecting blood biochemical and metabolic profiles in the newborn period. However, whether this exposure to RGZ in neonatal life alters the adult metabolic phenotype is not known. Objective: To determine the effects of early postnatal administration of RGZ on the young adult metabolic phenotype. Methods: Newborn rat pups were administered either saline or RGZ for the first 7 days of life. At 11–14 weeks, glucose and insulin tolerance tests and deuterium labeling were performed. Blood and tissues were analyzed for various metabolic parameters. Results: Overall, there was no effect of early postnatal RGZ administration on young adult body weight, glucose and insulin tolerance, plasma cholesterol and triglyceride profiles, insulin, glucagon, cardiac troponin, fatty acid synthesis, or tissue adipogenic differentiation. Conclusions: Treatment with RGZ in early neonatal life does not alter later developmental metabolic programming or lead to an altered metabolic phenotype in the young adult, further re-enforcing the safety of PPARγ agonists as a novel lung-protective strategy.

Copyright © 2011 S. Karger AG, Basel


 goto top of outline References
  1. Chen H, Jackson S, Doro M, McGowan S: Perinatal expression of genes that may participate in lipid metabolism by lipid-laden lung fibroblasts. J Lipid Res 1998;39:2483–2492.
  2. Tontonoz P, Hu E, Spiegelman BM: Regulation of adipocyte gene expression and differentiation by peroxisome proliferator activated receptor gamma. Curr Opin Genet Dev 1995;5:571–576.
  3. Simon DM, Arikan MC, Srisuma S, Bhattacharya S, Tsai LW, Ingenito EP, Gonzalez F, Shapiro SD, Mariani TJ: Epithelial cell PPARγ contributes to normal lung maturation. FASEB J 2006;20:1507–1509.
  4. Torday JS, Torres E, Rehan VK: The role of fibroblast transdifferentiation in lung epithelial cell proliferation, differentiation, and repair in vitro. Pediatr Pathol Mol Med 2003;22:189–207.
  5. Wang Y, Santos J, Sakurai R, Shin E, Cerny L, Torday JS, Rehan VK: Peroxisome proliferator-activated receptor gamma agonists enhance lung maturation in a neonatal rat model. Pediatr Res 2009;65:150–155.
  6. Garg M, Thamotharan M, Pan G, Lee PW, Devaskar SU: Early exposure of the pregestational intrauterine and postnatal growth-restricted female offspring to a peroxisome proliferator-activated receptor-γ agonist. Am J Physiol Endocrinol Metab 2010;298:E489–E498.
  7. Effect of corticosteroids for fetal maturation on perinatal outcomes. NIH Consensus Development Panel on the Effect of Corticosteroids for Fetal Maturation on Perinatal Outcomes. JAMA 1995;273:413–418.
  8. Ballard PL, Ballard RA, Granberg JP, Sniderman S, Gluckman PD, Kaplan SL, Grumbach MM: Fetal sex and prenatal betamethasone therapy. J Pediatr 1980;97:451–454.
  9. Wapner RJ, Sorokin Y, Mele L, Johnson F, Dudley DJ, Spong CY, Peaceman AM, Leveno KJ, Malone F, Caritis SN, Mercer B, Harper M, Rouse DJ, Thorp JM, Ramin S, Carpenter MW, Gabbe SG: Long-term outcomes after repeat doses of antenatal corticosteroids. N Engl J Med 2007;357:1190–1198.
  10. Willet KE, Jobe AH, Ikegami M, Newnham J, Sly PD: Antenatal retinoic acid does not alter alveolization or postnatal lung function in preterm sheep. Eur Respir J 2000;16:101–107.
  11. Lee WN, Bassilian S, Ajie HO, Schoeller DA, Edmond J, Bergner EA, Byerley LO: In vivo measurement of fatty acids and cholesterol synthesis using D2O and mass isotopomer analysis. Am J Physiol 1994;266:E699–E708.
  12. Rehan VK, Wang Y, Sugano S, Santos J, Patel S, Sakurai R, Boros LG, Lee WP, Torday JS: In utero nicotine exposure alters fetal rat lung alveolar type II cell proliferation, differentiation, and metabolism. Am J Physiol Lung Cell Mol Physiol 2007;292:L323–L333.
  13. Tontonoz P, Spiegelman BM: Fat and beyond: the diverse biology of PPARγ. Annu Rev Biochem 2008;77:289–312.
  14. Roberts D, Dalziel S: Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev 2006;3:CD004454.
  15. Cerny L, Torday JS, Rehan VK: Prevention and treatment of bronchopulmonary dysplasia: contemporary status and future outlook. Lung 2008;186:75–89.
  16. Khan MA, St Peter JV, Xue JL: A prospective, randomized comparison of the metabolic effects of pioglitazone or rosiglitazone in patients with type 2 diabetes who were previously treated with troglitazone. Diabetes Care 2002;25:708–711.
  17. Olansky L, Marchetti A, Lau H: Multicenter retrospective assessment of thiazolidinedione monotherapy and combination therapy in patients with type 2 diabetes: comparative subgroup analyses of glycemic control and blood lipid levels. Clin Ther 2003;25(suppl B):B64–B80.
  18. Komajda M, McMurray JJ, Beck-Nielsen H, Gomis R, Hanefeld M, Pocock SJ, Curtis PS, Jones NP, Home PD: Heart failure events with rosiglitazone in type 2 diabetes: data from the RECORD clinical trial. Eur Heart J 2010;31:824–831.
  19. Nissen SE, Wolski K: Rosiglitazone revisited: an updated meta-analysis of risk for myocardial infarction and cardiovascular mortality. Arch Intern Med 2010;170:1191–1201.
  20. Grundy SM: Metabolic syndrome pandemic. Arterioscler Thromb Vasc Biol 2008;28:629–636.
  21. Standiford TJ, Keshamouni VG, Reddy RC: Peroxisome proliferator-activated receptor-γ as a regulator of lung inflammation and repair. Proc Am Thorac Soc 2005;2:226–231.
  22. Genovese T, Cuzzocrea S, Di Paola R, Mazzon E, Mastruzzo C, Catalano P, Sortino M, Crimi N, Caputi AP, Thiemermann C, Vancheri C: Effect of rosiglitazone and 15-deoxy-δ12,14-prostaglandin J2 on bleomycin-induced lung injury. Eur Respir J 2005;25:225–234.
  23. Liu D, Zeng BX, Zhang SH, Yao SL: Rosiglitazone, an agonist of peroxisome proliferator-activated receptor gamma, reduces pulmonary inflammatory response in a rat model of endotoxemia. Inflamm Res 2005;54:464–470.
  24. Wayman NS, Hattori Y, McDonald MC, Mota-Filipe H, Cuzzocrea S, Pisano B, Chatterjee PK, Thiemermann C: Ligands of the peroxisome proliferator-activated receptors (PPAR-gamma and PPAR-α) reduce myocardial infarct size. FASEB J 2002;16:1027–1040.
  25. Dasgupta C, Sakurai R, Wang Y, Guo P, Ambalavanan N, Torday JS, Rehan VK: Hyperoxia-induced neonatal rat lung injury involves activation of TGF-β and Wnt signaling and is protected by rosiglitazone. Am J Physiol Lung Cell Mol Physiol 2009;296:L1031–L1041.

 goto top of outline Author Contacts

Virender K. Rehan, MD, Department of Pediatrics
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
David Geffen School of Medicine at UCLA
1124 West Carson Street, Torrance, CA 90502 (USA)
Tel. +1 310 222 1965, E-Mail vrehan@labiomed.org


 goto top of outline Article Information

Received: March 5, 2011
Accepted after revision: July 27, 2011
Published online: November 10, 2011
Number of Print Pages : 8
Number of Figures : 3, Number of Tables : 2, Number of References : 25


 goto top of outline Publication Details

Neonatology (Fetal and Neonatal Research)

Vol. 101, No. 3, Year 2012 (Cover Date: March 2012)

Journal Editor: Halliday H.L. (Belfast), Speer C.P. (Würzburg)
ISSN: 1661-7800 (Print), eISSN: 1661-7819 (Online)

For additional information: http://www.karger.com/NEO


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