Increased Formation of Triglyceride from Oleate in Perfused Livers from Pregnant Rats*

Abstract

Livers from normal ad libitum fed nonpregnant rats, from rats on days 10, 15, and 20 of gestation, and from rats 4 days post partum were isolated and perfused in vitro with a medium maintained at 0.3 mM oleic acid. Hepatic uptake of oleic acid and output of triglyceride, ketone bodies, and glucose were measured. Uptake of oleic acid was unaffected by pregnancy or lactation. The outputs of triglyceride per g liver were similar regardless of the stage of gestation or lactation. However, since on days 15 and 20 of gestation, livers were 27.3 ± 4.6% and 39.9 ± 6.7% heavier, respectively, than the controls, total hepatic output of triglyceride was increased compared to that in livers from nonpregnant rats. To evaluate metabolic changes appropriately and to circumvent the effect of increased liver weight induced by pregnancy, the data were recalculated as micromoles of triglyceride secreted per μmol FFA taken up. Expressed in this manner, it became clear that hepatic metabolism of FFA was altered and the output of triglyceride by livers from 15- and 20-day pregnant rats was increased, but the output by livers from rats pregnant for 10 days or from lactating rats was not different from that in controls. In contrast, ketogenesis was diminished by pregnancy and lactation. The diminution of ketone body production became evident as gestation proceeded, whether expressed per g liver, per liver, or per μmol FFA taken up. During pregnancy, plasma triglyceride concentration increased but was restored to control values 4 days post partum. In contrast, plasma total cholesterol and FFA were elevated significantly on day 20 of pregnancy and remained so post partum. The hepatic triglyceride concentration in vivo was not affected by pregnancy or lactation. However, during perfusion, livers from rats pregnant for 15 and 20 days accumulated more triglyceride than controls, while accumulation of triglyceride in livers from rats pregnant for 10 days or from lactating rats was not different from that in controls. The output of glucose by perfused livers from 15- or 20-day pregnant rats and lactating rats was decreased whether expressed per g liver or per total liver. It is suggested that the increased secretion of hepatic triglyceride observed during late gestation may result from the increased synthesis of triglyceride, the decreased oxidation of FFA, or both, and could account, in part, for the hypertriglyceridemia of pregnancy.