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

Truong, Nghia; Abbasi, Afshan; Sakurai, Reiko; Lee, W.N. Paul; Torday, John S.; Rehan, Virender K.

doi:10.1159/000331772

Cited by 6 publications

(7 citation statements)

References 46 publications

(26 reference statements)

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“…cardiovascular effects with RGZ, and bladder cancer with PGZ ( 14 – 17 , 26 ). In line with our prior studies, where we have shown that RGZ given parenterally, either antenatally or postnatally, doesn’t affect either cardiac troponin or any of the other metabolic parameters examined, such as the blood lipid profile and glucose and insulin tolerance tests ( 3 , 11 – 13 ), in this study too, plasma cardiac troponin levels were undetectable in both control and hyperoxia-exposed animals with or without PGZ treatment.…”

Section: Discussionsupporting

confidence: 92%

Nebulized PPARγ agonists: a novel approach to augment neonatal lung maturation and injury repair in rats

et al. 2014

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BACKGROUNDBy stimulating lipofibroblast maturation, parenterally administered PPARγ agonists promote lung homeostasis and injury repair in the neonatal lung. In this study, we determined whether PPARγ agonists could be delivered effectively via nebulization to neonates, and whether this approach would also protect against hyperoxia-induced lung injury.METHODSOne-day old Sprague-Dawley rat pups were administered PPARγ agonists rosiglitazone (RGZ, 3 mg/kg), pioglitazone (PGZ, 3 mg/kg), or the diluent, via nebulization every 24h; animals were exposed to 21% or 95% O2 for up to 72h. Twenty-four and 72h following initial nebulization, the pups were sacrificed for lung tissue and blood collection to determine markers of lung maturation, injury repair, and RGZ and PGZ plasma levels.RESULTSNebulized RGZ and PGZ enhanced lung maturation in both males and females, as evidenced by the increased expression of markers of alveolar epithelial and mesenchymal maturation. This approach also protected against hyperoxia-induced lung injury, since hyperoxia-induced changes in bronchoalveolar lavage cell and protein contents and lung injury markers were all blocked by nebulized PGZ.CONCLUSIONSNebulized PPARγ agonist administration promotes lung maturation and prevents neonatal hyperoxia-induced lung injury in both males and females.

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Section: Discussionsupporting

confidence: 92%

Nebulized PPARγ agonists: a novel approach to augment neonatal lung maturation and injury repair in rats

et al. 2014

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“…Since hypoxia and hyperoxia have similar consequences for the TGF-β/WNT/β-catenin/PPARγ pathways, this requires a fine tuning of oxygen use in very premature infants. Numerous studies have shown PPARγ agonists have a beneficial effect on lung maturation and may provide a potentially safe lung therapy (53, 54, 115, 146, 147, 157, 196, 197). Nebulized PPARγ agonists may represent a potential strategy for improving postnatal lung maturation, both by inhibition of the TGF-β/WNT/β-catenin pathway and by preventing neonatal hyperoxia-induced lung injury in premature BPD infants, thereby reducing morbidity and mortality.…”

Section: Resultsmentioning

confidence: 99%

“…In an animal model, the systemic administration of RGZ, either antenatally or postnatally, enhances lung maturation and can prevent hyperoxia-induced acute neonatal lung injury. This strongly suggests that PPARγ agonists could potentially play an important role in preventing and/or treating BPD (53, 115, 146, 147).…”

Section: Pparγ Agonists and Bpdmentioning

confidence: 99%

Bronchopulmonary Dysplasia: Crosstalk Between PPARγ, WNT/β-Catenin and TGF-β Pathways; The Potential Therapeutic Role of PPARγ Agonists

Lecarpentier¹,

Gourrier²,

Gobert³

et al. 2019

Front. Pediatr.

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Bronchopulmonary dysplasia (BPD) is a serious pulmonary disease which occurs in preterm infants. Mortality remains high due to a lack of effective treatment, despite significant progress in neonatal resuscitation. In BPD, a persistently high level of canonical WNT/β-catenin pathway activity at the canalicular stage disturbs the pulmonary maturation at the saccular and alveolar stages. The excessive thickness of the alveolar wall impairs the normal diffusion of oxygen and carbon dioxide, leading to hypoxia. Transforming growth factor (TGF-β) up-regulates canonical WNT signaling and inhibits the peroxysome proliferator activated receptor gamma (PPARγ). This profile is observed in BPD, especially in animal models. Following a premature birth, hypoxia activates the canonical WNT/TGF-β axis at the expense of PPARγ. This gives rise to the differentiation of fibroblasts into myofibroblasts, which can lead to pulmonary fibrosis that impairs the respiratory function after birth, during childhood and even adulthood. Potential therapeutic treatment could target the inhibition of the canonical WNT/TGF-β pathway and the stimulation of PPARγ activity, in particular by the administration of nebulized PPARγ agonists.

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“…Recent studies have also shown that PPAR γ agonists such as rosiglitazone (RGZ) significantly enhance lung maturation when administered antenatally. Its efficacy in enhancing pulmonary maturation and neonatal and long-term safety following postnatal administration has also been demonstrated recently [ 5 , 6 ]. In those studies, lack of any significant impact on the neonatal and long-term metabolic profile of the exposed offspring was demonstrated [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

“…Its efficacy in enhancing pulmonary maturation and neonatal and long-term safety following postnatal administration has also been demonstrated recently [ 5 , 6 ]. In those studies, lack of any significant impact on the neonatal and long-term metabolic profile of the exposed offspring was demonstrated [ 5 , 6 ]. However, data on the long-term effects of RGZ are sparse, and to date no study has examined the effects of RGZ on the metabolic profile of adult rats when administered prenatally.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2012

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Prenatally administered rosiglitazone (RGZ) is effective in enhancing lung maturity; however, its long-term safety remains unknown. This study aimed to determine the effects of prenatally administered RGZ on the metabolic phenotype of adult rats. Methods. Pregnant Sprague-Dawley rat dams were administered either placebo or RGZ at embryonic days 18 and 19. Between 12 and 20 weeks of age, the rats underwent glucose and insulin tolerance tests and de novo fatty acid synthesis assays. The lungs, liver, skeletal muscle, and fat tissue were processed by Western hybridization for peroxisome proliferator-activated receptor (PPAR)γ, adipose differentiation-related protein (ADRP), and surfactant proteins B (SPB) and C (SPC). Plasma was assayed for triglycerides, cholesterol, insulin, glucagon, and troponin-I levels. Lungs were also morphometrically analyzed. Results. Insulin and glucose challenges, de novo fatty acid synthesis, and all serum assays revealed no differences among all groups. Western hybridization for PPARγ, ADRP, SPB, and SPC in lung, liver, muscle, and fat tissue showed equal levels. Histologic analyses showed a similar number of alveoli and septal thickness in all experimental groups. Conclusions. When administered prenatally, RGZ does not affect long-term fetal programming and may be safe for enhancing fetal lung maturation.

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

Cited by 6 publications

References 46 publications

Nebulized PPARγ agonists: a novel approach to augment neonatal lung maturation and injury repair in rats

Nebulized PPARγ agonists: a novel approach to augment neonatal lung maturation and injury repair in rats

Bronchopulmonary Dysplasia: Crosstalk Between PPARγ, WNT/β-Catenin and TGF-β Pathways; The Potential Therapeutic Role of PPARγ Agonists

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

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