Premature Appearance of Gluconeogenesis and Fatty Acid Oxidation in the Liver of the Postterm Rabbit Fetus

Abstract

ABSTRACT: The metabolic consequences of a prolonged gestation (35 vs 32 days) have been studied in the rabbit fetus. Gestation was prolonged by daily subcutaneous injections of progesterone (1.5 mg · kg⁻¹) from day 28 to 34. In control animals, progesterone was injected from day 25 or 28 to day 31 of gestation. When the capacities for gluconeogenesis and fatty acid oxidation, measured on isolated hepatocytes, are normally low in the term control fetus and increase only within the first 24 h after birth, these capacities appear high in the postmature fetus. The rate of glucose production from lactate is 4-fold higher in the postmature fetus than in the normal term fetus. The rate of ketone body production from oleate is also 5-fold higher in the postmature fetus, which results from a switch on of the partition of oleate into esterification and oxidation: 8% of [1–¹⁴C]oleate is oxidized in term fetus hepatocytes, but 34% in postmature fetus hepatocytes. As a similar rate of lipogenesis takes place in both stages, this metabolic change could be explained by a 5-fold lower sensitivity of carnitine palmitoyltransferase I to the inhibition by malonyl-coenzyme A. Postmaturity decreases plasma insulin concentrations by 45% and increases plasma glucagon concentrations by 50% which, in turn, induces a 3-fold decrease in the plasma insulin:glucagon molar ratio. As previously shown in fasted or diabetic adult rat, this hormonal change might be a likely candidate for an enhancement of gluconeogenic and ketogenic capacity in the liver of the postterm rabbit fetus.