Ketone body metabolism during pregnancy in the rabbit

The aim of this study was to test the effect of lipid store mobilization on changes in ketone body metabolism in pregnant rabbits. Related blood parameters were studied in pregnant animals fed either ad libitum or submitted between days 21 of gestation and parturition first to 50% food restriction for 4 days and then to a complete fast. Ketogenesis from oleate, butyrate and endogenous substrates was measured on days 0, 8, 18 and 28 of gestation in isolated liver cells prepared from females fasted for 48 h. In the does fed ad libitum, the concentration of non-esterified fatty acids (NEFA) was higher than in non-pregnant animals and then increased about 2-fold in the last week before term. Total ketone body concentrations increased slightly but significantly from day 27 until term. In the same period, glycemia decreased significantly. No variations were observed in lactate, alanine and total amino acid concentrations. Food restriction on days 21 to 24 induced a quick rise in the plasma concentrations of NEFA, ketone bodies and glycerol. Further fasting resulted in the development of hyperketonemia which was more than 3 times that observed during prolonged fasting in non-pregnant rabbits. There was no further increase in plasma NEFA level after day 27 of gestation. Food restriction and fasting decreased only the plasma level of total amino acids but had no significant effect on plasma concentrations of lactate and alanine. In isolated liver cells, a marked and significant increase in the rate of ketogenesis from oleate, butyrate and endogenous substrates was noted on day 28 of gestation in comparison with the preceding periods. It is concluded that ketonemia was enhanced in late gestation, particularly with restricted feeding or in fasted animals; this enhancement was partly related to the increase of plasma NEFA concentrations and partly to the enhancement of hepatic ketogenesis in the mothers. The fact that the rate of hepatic ketogenesis was increased equally with butyrate and oleate indicated that it could not be explained by a modification of acylcarnitine transferase activity as butyrate directly crosses the mitochondrial membrane without using this pathway.