Fetal Growth Restriction and High Fat Diet Decrease PPARg Expression in Newborn Rat Lung

Uteroplacental insufficiency (UPI) is a common cause of fetal growth restriction (FGR). FGR is associated with early events that impair lung development. The transcription factor PPARg is essential for normal lung development and function. High fat diet (HFD) also impairs lung development and function. PPARg is decreased in the lung by FGR. However, the effects of maternal HFD with or without FGR on offspring lung PPARg are unknown.  We hypothesize that FGR and/or maternal HFD will decrease PPARg protein in newborn rat lungs.  UPI was induced by bilateral uterine artery ligation at E19 of gestation to produce FGR pups. Maternal rat were fed Standard Rat Chow or HFD. PPARg protein isoforms (PPARg1 & PPARg2) were quantified Western Blotting.  Results are mean percent of gender-matched control ± SD.  In female rat pups, PPARg2 protein levels was decreased by FGR (72±24%, p=0.16) and HFD (37±32%, p=.03). In combination, FGR and HFD reduced PPARg2 levels even further (13±13%, p=0.01). In male rat pups, PPARg2 protein levels was decreased by FGR (40±19, p=0.01) and HFD (72±43%, p=0.35). In combination, FGR and HFD reduced PPARg2 levels even further (38±22%, p=0.04).  In conclusion, FGR and HFD, as well as the combination, reduces PPARg2 expression in newborn rat lung. Therefore, we speculate that maternal HFD further impairs lung development via alterations in PPARg expression in FGR infants. Understanding the role of lung development and function at the molecular level is necessary to improve long-term pulmonary health in FGR infants.