Intrauterine Growth Restriction Increases Fetal Hepatic Gluconeogenic Capacity and Reduces Messenger Ribonucleic Acid Translation Initiation and Nutrient Sensing in Fetal Liver and Skeletal Muscle
AUTOR(ES)
Thorn, Stephanie R.
FONTE
The Endocrine Society
RESUMO
Expression of key metabolic genes and proteins involved in mRNA translation, energy sensing, and glucose metabolism in liver and skeletal muscle were investigated in a late-gestation fetal sheep model of placental insufficiency intrauterine growth restriction (PI-IUGR). PI-IUGR fetuses weighed 55% less; had reduced oxygen, glucose, isoleucine, insulin, and IGF-I levels; and had 40% reduction in net branched chain amino acid uptake. In PI-IUGR skeletal muscle, levels of insulin receptor were increased 80%, whereas phosphoinositide-3 kinase (p85) and protein kinase B (AKT2) were reduced by 40%. Expression of eukaryotic initiation factor-4e was reduced 45% in liver, suggesting a unique mechanism limiting translation initiation in PI-IUGR liver. There was either no change (AMP activated kinase, mammalian target of rapamycin) or a paradoxical decrease (protein phosphatase 2A, eukaryotic initiation factor-2α) in activation of major energy and cell stress sensors in PI-IUGR liver and skeletal muscle. A 13- to 20-fold increase in phosphoenolpyruvate carboxykinase and glucose 6 phosphatase mRNA expression in the PI-IUGR liver was-associated with a 3-fold increase in peroxisome proliferator-activated receptor-γ coactivator-1α mRNA and increased phosphorylation of cAMP response element binding protein. Thus PI-IUGR is-associated with reduced branched chain amino acid uptake and growth factors, yet up-regulation of proximal insulin signaling and a marked increase in the gluconeogenic pathway. Lack of activation of several energy and stress sensors in fetal liver and skeletal muscle, despite hypoxia and low energy status, suggests a novel strategy for survival in the PI-IUGR fetus but with potential maladaptive consequences for reduced nutrient sensing and insulin sensitivity in postnatal life.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2703533Documentos Relacionados
- Discrimination between Messenger Ribonucleic Acids by a Mammalian Translation Initiation Factor
- Effects of Maternal Global Nutrient Restriction on Fetal Baboon Hepatic Insulin-Like Growth Factor System Genes and Gene Products
- The transition from fetal growth restriction to accelerated postnatal growth: a potential role for insulin signalling in skeletal muscle
- Characterization and in vitro translation of polyadenylated messenger ribonucleic acid from Neurospora crassa.
- Messenger Ribonucleic Acid Synthesis and Degradation in Escherichia coli During Inhibition of Translation