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.