Prolonged infusion of amino acids increases leucine oxidation in fetal sheep

Am J Physiol Endocrinol Metab. 2012 Jun 15;302(12):E1483-92. doi: 10.1152/ajpendo.00026.2012. Epub 2012 Mar 27.

Abstract

Maternal high-protein supplements designed to increase birth weight have not been successful. We recently showed that maternal amino acid infusion into pregnant sheep resulted in competitive inhibition of amino acid transport across the placenta and did not increase fetal protein accretion rates. To bypass placental transport, singleton fetal sheep were intravenously infused with an amino acid mixture (AA, n = 8) or saline [control (Con), n = 10] for ∼12 days during late gestation. Fetal leucine oxidation rate increased in the AA group (3.1 ± 0.5 vs. 1.4 ± 0.6 μmol·min(-1)·kg(-1), P < 0.05). Fetal protein accretion (2.6 ± 0.5 and 2.2 ± 0.6 μmol·min(-1)·kg(-1) in AA and Con, respectively), synthesis (6.2 ± 0.8 and 7.0 ± 0.9 μmol·min(-1)·kg(-1) in AA and Con, respectively), and degradation (3.6 ± 0.6 and 4.5 ± 1.0 μmol·min(-1)·kg(-1) in AA and Con, respectively) rates were similar between groups. Net fetal glucose uptake decreased in the AA group (2.8 ± 0.4 vs. 3.9 ± 0.1 mg·kg(-1)·min(-1), P < 0.05). The glucose-O(2) quotient also decreased over time in the AA group (P < 0.05). Fetal insulin and IGF-I concentrations did not change. Fetal glucagon increased in the AA group (119 ± 24 vs. 59 ± 9 pg/ml, P < 0.05), and norepinephrine (NE) also tended to increase in the AA group (785 ± 181 vs. 419 ± 76 pg/ml, P = 0.06). Net fetal glucose uptake rates were inversely proportional to fetal glucagon (r(2) = 0.38, P < 0.05), cortisol (r(2) = 0.31, P < 0.05), and NE (r(2) = 0.59, P < 0.05) concentrations. Expressions of components in the mammalian target of rapamycin signaling pathway in fetal skeletal muscle were similar between groups. In summary, prolonged infusion of amino acids directly into normally growing fetal sheep increased leucine oxidation. Amino acid-stimulated increases in fetal glucagon, cortisol, and NE may contribute to a shift in substrate oxidation by the fetus from glucose to amino acids.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid-Base Equilibrium / physiology
  • Amino Acids / blood
  • Amino Acids / pharmacology*
  • Animals
  • Blood Gas Analysis
  • Blotting, Western
  • Carbon Dioxide / blood
  • Female
  • Fetus / metabolism*
  • Glucose / metabolism
  • Glucose-6-Phosphatase / metabolism
  • Hormones / blood
  • Infusions, Intravenous
  • Kinetics
  • Lactic Acid / metabolism
  • Leucine / metabolism*
  • Organ Size / physiology
  • Oxidation-Reduction
  • Phosphoenolpyruvate Carboxykinase (ATP) / genetics
  • Pregnancy
  • Pulmonary Gas Exchange
  • Real-Time Polymerase Chain Reaction
  • Sheep / metabolism*
  • Tissue Distribution

Substances

  • Amino Acids
  • Hormones
  • Carbon Dioxide
  • Lactic Acid
  • Glucose-6-Phosphatase
  • Phosphoenolpyruvate Carboxykinase (ATP)
  • Leucine
  • Glucose