Changes in PGC-1α-Dependent Mitochondrial Biogenesis Are Associated with Inflexible Hepatic Energy Metabolism in the Offspring Born to Dexamethasone-Treated Mothers

In the present study we investigated participation of hepatic peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α) in metabolic programming newborn rats exposed utero to dexamethasone (DEX). On 21st day life, fasted offspring born DEX-treated mothers displayed increased conversion pyruvate into glucose with simultaneous upregulation PEPCK (phosphoenolpyruvate carboxykinase) and G6Pase (glucose-6-phosphatase). Increased oxidative phosphorylation, higher ATP/ADP ratio mitochondrial biogenesis lower levels were also found progeny mothers. other hand, 21-day-old had triglycerides (TAG) CPT-1 activity when subjected short-term fasting. At mechanistic level, DEX exhibited PGC-1α protein content miR-29a-c expression. was concurrent association HNF-4α NRF1 reduced PPARα The data presented herein reveal that changes transcription machinery neonatal liver leads an inflexible response Such is hallmarked by phosphorylation impaired FFA oxidation TAG accumulation.