Postnatal rosiglitazone administration to neonatal rat pups does not alter the young adult metabolic phenotype - PubMed (original) (raw)

Postnatal rosiglitazone administration to neonatal rat pups does not alter the young adult metabolic phenotype

Nghia C Truong et al. Neonatology. 2012.

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.

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Figures

Fig. 1

a Effect of RGZ on glucose tolerance test: at 11 weeks of age, glucose was administered at 1 g/kg body weight intraperitoneally after an overnight fast. Glucose was assayed at time 0 (baseline), 15, 30, 60, 120 and 180 min. There were no significant differences (p > 0.05) in timed serum glucose values in the treated groups compared with controls during the GTT. b Effect of RGZ on insulin tolerance test: at 12 weeks of age, insulin was administered at 1 unit/kg body weight subcutaneously after an overnight fast. Glucose was assayed at time 0 (baseline), 15, 30, 60, 120 and 180 min. There were no significant differences (p > 0.05) in timed serum glucose values between the treated and control groups during the ITT. a, b ⋄ = Control group, □ = RGZ 0.3 mg/kg group, ▵ = RGZ 1 mg/kg group, × = RGZ 3 mg/kg group.

Fig. 2

Effect of RGZ on lung maturation: the newborn rat pups were administered either diluent or RGZ in graded doses in 100-μl volumes once daily intraperitoneally for 7 days, and then lung maturation was assessed at 14 weeks of age by determining the alveolar count and selective markers of alveolar epithelial (choline incorporation into disaturated phosphatidylcholine by lung explants and lamellar body and surfactant protein B and C immunostaining) and mesenchymal (triolein uptake by lung explants and protein levels of PPARγ and ADRP) differentiation. There were no significant differences in the alveolar counts, triolein uptake, choline incorporation into disaturated phosphatidylcholine (a), and markers of alveolar mesenchymal (PPARγ and ADRP, b, representative Western blots and the corresponding density histograms normalized to GAPDH are shown) and epithelial (lamellar body and surfactant protein B and C immunostaining, c, representative images are shown) differentiation between the groups.

Fig. 3

Effect of RGZ on PPARγ and ADRP expression in liver, peritoneal and subcutaneous adipose tissue: the newborn rat pups were administered either diluent or RGZ in graded doses in 100-μl volumes once daily intraperitoneally for 7 days, and then PPARγ and ADRP expression were examined in the whole tissue lysates of the liver (a), peritoneal fat (b) and subcutaneous fat (c). There were no significant differences (p > 0.05) in protein levels of PPARγ or ADRP in the liver, or the peritoneal or subcutaneous fat, normalized to GAPDH, as determined by Western hybridization in the treated groups compared with the controls. Representative Western blots and the corresponding density histograms are shown.

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Postnatal rosiglitazone administration to neonatal rat pups does not alter the young adult metabolic phenotype - PubMed (original) (raw)