Cardiac growth and metabolism of the fetal sheep are not vulnerable to a 10 day increase in fetal glucose and insulin concentrations during late gestation

Abstract

Aims: To evaluate the effects of fetal glucose infusion in late gestation on the mRNA expression and protein abundance of molecules involved in the regulation of cardiac growth and metabolism. Main methods: Either saline or glucose was infused into fetal sheep from 130 to 140 days (d) gestation (term, 150 d). At 140 d gestation, left ventricle tissue samples were collected. Quantitative real-time RT-PCR and Western blot were used to determine the mRNA expression and protein abundance of key signalling molecules within the left ventricle of the fetal heart. Key findings: Although intra-fetal glucose infusion increased fetal plasma glucose and insulin concentrations, there was no change in the expression of molecules within the signalling pathways that regulate proliferation, hypertrophy, apoptosis or fibrosis in the fetal heart. Cardiac Solute carrier family 2 member 1 (SLC2A1) mRNA expression was decreased by glucose infusion. Glucose infusion increased cardiac mRNA expression of both Peroxisome proliferator activated receptor alpha (PPARA) and peroxisome proliferator activated receptor gamma (PPARG). However, there was no change in the mRNA expression of PPAR cofactors or molecules with PPAR response elements. Furthermore, glucose infusion did not impact the protein abundance of the 5 oxidative phosphorylation complexes of the electron transport chain. Significance: Despite a 10-day doubling of fetal plasma glucose and insulin concentrations, the present study suggests that within the fetal left ventricle, the mRNA and protein expression of the signalling molecules involved in cardiac growth, development and metabolism are relatively unaffected.