Acute supplementation of amino acids increases net protein accretion in IUGR fetal sheep.
Placental insufficiency decreases fetal amino acid uptake from the placenta, plasma insulin concentrations, and protein accretion, thus compromising normal fetal growth trajectory. We tested whether acute supplementation of amino acids or insulin into the fetus with intrauterine growth restriction (IUGR) would increase net fetal protein accretion rates. Late-gestation IUGR and control (CON) fetal sheep received acute, 3-h infusions of amino acids (with euinsulinemia), insulin (with euglycemia and euaminoacidemia), or saline. Fetal leucine metabolism was measured under steady-state conditions followed by a fetal muscle biopsy to quantify insulin signaling. In CON, increasing amino acid delivery rates to the fetus by 100% increased leucine oxidation rates by 100%. In IUGR, amino acid infusion completely suppressed fetal protein breakdown rates but increased leucine oxidation rate by only 25%, resulting in increased protein accretion rates by 150%. Acute insulin infusion, however, had very little effect on amino acid delivery rates, fetal leucine disposal rates, or fetal protein accretion rates in CON or IUGR fetuses despite robust signaling of the fetal skeletal muscle insulin-signaling cascade. These results indicate that, when amino acids are given directly into the fetal circulation independently of changes in insulin concentrations, IUGR fetal sheep have suppressed protein breakdown rates, thus increasing net fetal protein accretion.
Perinatal Research Center, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO 80045, USA. laura.brown@ucdenver.edu
Laura D
LD
Brown
Paul J
PJ
Rozance
Stephanie R
SR
Thorn
Jacob E
JE
Friedman
William W
WW
Hay
D000596:Amino Acids / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D002247:Carbon Isotopes / Q000008:administration & dosage / Q000493:pharmacokinetics; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism* / Q000473:pathology; D007328:Insulin / Q000008:administration & dosage; D007930:Leucine / Q000008:administration & dosage / Q000493:pharmacokinetics; D011247:Pregnancy; D014176:Protein Biosynthesis / Q000187:drug effects / Q000502:physiology; D011506:Proteins / Q000378:metabolism*; D059748:Proteolysis / Q000187:drug effects; D011897:Random Allocation; D012756:Sheep; D013997:Time Factors
D000596:Amino Acids; D002247:Carbon Isotopes; D007328:Insulin; D011506:Proteins; D007930:Leucine