title: Maternal undernutrition around the time of conception and embryo number each impact on the abundance of key regulators of cardiac growth and metabolism in the fetal sheep heart.
abstract: Poor maternal nutrition before and during pregnancy is associated with an increased risk of cardiovascular disease in later life. To determine the impact of maternal undernutrition during the periconceptional (PCUN: -45 days to 6 days) and preimplantation (PIUN: 0-6 days) periods on cardiac growth and metabolism, we have quantified the mRNA and protein abundance of key regulators of cardiac growth and metabolism in the left ventricle of the sheep fetus in late gestation. The cardiac protein abundance of AMP-activated protein kinase (AMPK), phospho-acetyl CoA carboxykinase (ACC) and pyruvate dehydrogenase kinase-4 (PDK-4) were decreased, whereas ACC was increased in singletons in the PCUN and PIUN groups. In twins, however, cardiac ACC was decreased in the PCUN and PIUN groups, and carnitine palmitoyltransferase-1 (CPT-1) was increased in the PIUN group. In singletons, the cardiac abundance of insulin receptor β (IRβ) was decreased in the PCUN group, and phosphoinositide-dependent protein kinase-1 (PDPK-1) was decreased in the PCUN and PIUN groups. In twins, however, the cardiac abundance of IRβ and phospho-Akt substrate 160kDa (pAS160) were increased in the PIUN group. The cardiac abundance of insulin-like growth factor-2 receptor (IGF-2R), protein kinase C alpha (PKCα) and mammalian target of rapamycin (mTOR) were decreased in PCUN and PIUN singletons and extracellular-signal-regulated kinase (ERK) was also decreased in the PIUN singletons. In contrast, in twins, cardiac abundance of IGF-2R and PKCα were increased in the PCUN and PIUN groups, phospho-ribosomal protein S6 (pRPS6) was increased in the PCUN group, and ERK and eukaryotic initiation factor 4E (eIF4E) were also increased in the PIUN fetuses. In conclusion, maternal undernutrition limited to around the time of conception is sufficient to alter the abundance of key factors regulating cardiac growth and metabolism and this may increase the propensity for cardiovascular diseases in later life.
authors: 1 Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia.
authors: S
authors: S
authors: Lie
authors: 1 Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia.
authors: S M
authors: SM
authors: Sim
authors: 1 Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia.
authors: I C
authors: IC
authors: McMillen
authors: 1 Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia.
authors: O
authors: O
authors: Williams-Wyss
authors: 1 Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia.
authors: S M
authors: SM
authors: MacLaughlin
authors: 3 South Australian Research and Development Institute, Turretfield Research Centre, Rosedale, SA, Australia.
authors: D O
authors: DO
authors: Kleemann
authors: 3 South Australian Research and Development Institute, Turretfield Research Centre, Rosedale, SA, Australia.
authors: S K
authors: SK
authors: Walker
authors: 4 Discipline of Obstetrics and Gynaecology, University of Adelaide, Adelaide, SA, Australia.
authors: C T
authors: CT
authors: Roberts
authors: 1 Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia.
authors: J L
authors: JL
authors: Morrison