Cerebral Protein Synthesis in the Ovine Fetus Near Term with Amino Acid Infusion and Insulin-Induced Hypoaminoacidemia

Abstract

Background: Studies during early development have shown that the precursor availability of amino acids directly affects protein synthesis both at the whole-body level and for select organ tissues, although this has not been studied for the brain. Objective: We utilized a mixed amino acid infusate and an insulin euglycemic clamp technique in the ovine fetus near term, with increases and decreases in circulating amino acid levels of ∼30 to 40% on average, and determined the impact on cerebral protein synthesis. Methods: Fetal sheep received a 6-hour infusion of Primene® 10% (amino acid infusate group) or a co-infusion of insulin and 10% dextrose (insulin/dextrose infusate group) together with a continuous infusion of L-[1-¹³C]-leucine. Measurements were obtained for fetal plasma leucine enrichment at steady-state and brain tissue intracellular free and protein-bound leucine enrichment at necropsy, followed by the determination of cerebral protein fractional synthetic rates (FSR). Results: Protein FSR for the cerebral cortex averaged ∼58 and ∼39%/day when using the intracellular free and plasma enrichment values for the precursor pool measurements, respectively, providing for maximal and minimal FSR values, and with little difference between the amino acid and insulin/dextrose groups, although significantly higher than respective values for the cerebellum. Conclusion: Accordingly, there was no evidence of a differential effect of increases versus decreases in circulating amino acids on cerebral protein synthesis as studied, which may be attributed to the saturable nature of the blood-brain barrier transporters for amino acids.