PPARGC1A and Insulin resistance: Our observed reduction in maternal hepatic Hnf4α suggest perhaps that elevated maternal insulin levels, due to mDIO, may be acting through Pgc1α / Hnf4α pathways to reduce transcription of gluconeogenic target genes including Pepck. Although we did not observe changes in Pgc1α transcript levels, compromised activity of PGC-1α and HNF4 α have been associated with the development of insulin resistance and Type 2 diabetes76–78.