No 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.

Associations between exponential childhood growth superimposed on low birth weight and adult onset cardiovascular disease with glucose intolerance/type 2 diabetes mellitus exist in epidemiological investigations. To determine the metabolic adaptations that guard against myocardial failure on subsequent exposure to hypoxia, we compared with controls (CON), the effect of intrauterine (IUGR), postnatal (PNGR), and intrauterine and postnatal (IPGR) calorie and growth restriction (n = 6/group) on myocardial macronutrient transporter (fatty acid and glucose) -mediated uptake in pregestational young female adult rat offspring. A higher myocardial FAT/CD36 protein expression in IUGR, PNGR, and IPGR, with higher FATP1 in IUGR, FATP6 in PNGR, FABP-c in PNGR and IPGR, and no change in GLUT4 of all groups was observed. These adaptive macronutrient transporter protein changes were associated with no change in myocardial [(3)H]bromopalmitate accumulation but a diminution in 2-deoxy-[(14)C]glucose uptake. Examination of the sarcolemmal subfraction revealed higher basal concentrations of FAT/CD36 in PNGR and FATP1 and GLUT4 in IUGR, PNGR, and IPGR vs. CON. Exogenous insulin uniformly further enhanced sarcolemmal association of these macronutrient transporter proteins above that of basal, with the exception of insulin resistance of FATP1 and GLUT4 in IUGR and FAT/CD36 in PNGR. The basal sarcolemmal macronutrient transporter adaptations proved protective against subsequent chronic hypoxic exposure (7 days) only in IUGR and PNGR, with notable deterioration in IPGR and CON of the echocardiographic ejection fraction. We conclude that the IUGR and PNGR pregestational adult female offspring displayed a resistance to insulin-induced translocation of FATP1, GLUT4, or FAT/CD36 to the myocardial sarcolemma due to preexistent higher basal concentrations. This basal adaptation of myocardial macronutrient transporters ensured adequate fatty acid uptake, thereby proving protective against chronic hypoxia-induced myocardial compromise.

No abstract

No abstract