Ovine fetal protein metabolism during decreased glucose delivery

During decreased fetal glucose delivery, endogenous substrates increasingly support metabolic rate. If oxidation of fetal amino acid stores (i.e., protein) is to provide such substrate, either protein synthesis must decrease or protein breakdown must increase. Both of these changes would diminish fetal protein accretion, an important component of fetal growth. This study was performed, therefore, to find if decreased glucose delivery alters fetal leucine metabolism. Catheters were placed in six sheep fetuses under maternal general anesthesia, and, after 6 days recovery, fetal leucine metabolism was measured by infusion of [1-14C]leucine before and after fetal glucose delivery was decreased by infusing insulin to the ewe. Later (2 days) the experiment was repeated in reverse order. Decreased fetal glucose delivery was associated with a 19% decrease in the rate of fetal leucine disposal (P < 0.001), a 42% decrease in the rate of exogenous leucine uptake (P < 0.01), and no change in the rate of fetal leucine decarboxylation. The use of leucine for protein synthesis by the fetus fell by 23% (P < 0.001), whereas the rate of protein breakdown did not change. Consequently, during decreased fetal glucose delivery, leucine accretion into fetal proteins was 28% (P < 0.02) of the control rate. In summary, fetal oxidation of amino acids derived from increased protein breakdown is not the source of endogenous substrate needed by the fetus with restricted glucose availability. Fetal protein synthesis did decrease, however, diminishing the accretion of leucine into protein.