Metabolic responses to protein restriction during pregnancy in rat and translation initiation factors in the mother and fetus.

ABSTRACT

A low-protein diet during pregnancy in the rat results in intrauterine growth restricted (IUGR) fetuses. The adaptive responses of the mother to low-protein diet and the mechanisms of IUGR in this model are not understood. In the present study, we report the maternal metabolic responses to protein restriction and their impact on growth, carcass composition, and translation initiation in the fetus. Pregnant Sprague-Dawley rats were pair-fed either a 6% protein (LP, n = 7) or a 24% protein (NP, n = 7) diet from conception until delivery. Plasma amino acids and urea levels and rate of oxygen consumption were measured sequentially through pregnancy. Translation initiation factors eIF2alpha, Ser51 phosphorylated eIF2alpha, eIF4E, phosphorylated eIF4E, and 4E-BP1 were quantified in the maternal and fetal muscle and liver. Protein restriction resulted in higher rate of oxygen consumption (p < 0.01), lower plasma branched chain amino acid (p < 0.05) in the mother, and lower plasma histidine levels (p < 0.05) in the fetus. Plasma urea nitrogen was lower in the LP group throughout gestation. The phosphorylated 4E-BP1 (gamma form) in the maternal liver was 4-fold higher in the LP group. The phosphorylated eIF2alpha was higher in the livers of IUGR fetuses. We speculate that the lower plasma branched chain amino acids in the mother during early pregnancy may be due to a lower rate of protein turnover in the LP group. The mechanism of increased energy consumption due to protein restriction remains unclear. The data on translation initiation factors suggest a higher rate of protein synthesis in the maternal liver and a lower rate in the fetal liver in response to protein restriction.