Fetal metabolic response to maternal fasting in the rat.

To determine the fetal response to altered maternal fuel supply, the effects of prolonged maternal fasting, begun 24-96 h before term, were examined and compared with values from normally fed term animals. Fetal weight decreased only after 48 h of maternal fasting. Prolonged maternal fasting was associated with low blood glucose, high blood ketone bodies, and decreased gluconeogenic substrate in the fetus. Plasma insulin was decreased, whereas plasma glucagon was increased in the fetus of fasted mothers. Infusion of [2-3H]glucose into the mother to constant specific activity gave a ratio of maternal to fetal glucose activity of 1.0 in fed and 1.56 in fasted mothers. Fetal liver from fasted mothers showed both increase in activity of key gluconeogenic enzymes (glucose-6-phosphatase and phosphoenolpyruvate carboxykinase) and increased conversion in vitro of lactate, alanine, serine, and glycerol in glucose by liver slices. It is inferred that maternal fasting induces fetal substrate alterations and hormonal changes appropriate to premature appearance of hepatic gluconeogenesis. The priority for endogenous fuel provision in this state leads to impaired fetal growth.