Browsing by Author "Montelongo, Adela"

Cholesteryl ester transfer protein (CETP) activity was measured in a d > 1.21 kg/L plasma fraction collected from healthy women at different times during gestation, postpartum, and in control women. CETP activity was highest in the second trimester of gestation, declined at the third trimester, and was lowest at postpartum. Only the value at the second trimester was significantly different from that of control women. This trend differed from that of circulating lipoproteins: very low-density lipoprotein (VLDL)-lipids, including triglycerides and cholesterol, increased progressively from the first to the third trimester, and then declined at postpartum. Low-density lipoprotein (LDL)cholesterol levels, like VLDL levels, rose during gestation but then remained elevated at postpartum. High-density lipoprotein (HDL)-cholesterol as well as HDL-phospholipids and apolipoprotein A-1, peaked in the second trimester, remaining elevated in the third trimester and then fell at postpartum. Finally, HDL-triglyceride increased markedly from the first to the second trimester, rose somewhat higher during the third trimester, and declined at postpartum. When all the samples from pregnant women were considered together, CETP activity correlated significantly with HDL-triglyceride levels and the changes in CETP activity during gestation and postpartum paralleled those of the HDL-triglyceride/VLDL-triglyceride ratio. These results suggest that CETP contributes to the exaggerated accumulation of triglycerides in HDL that begins in the second trimester of human gestation.

The purpose of this review is to consider the alterations occurring in lipoprotein metabolism in human pregnancy and in selected animal models and to attempt to understand the reasons for these changes and the possible significance for maternal physiology and fetal growth and development. The effects of diabetes mellitus on the system will be briefly considered.

Plasma lipoproteins were studied longitudinally at the 1st, 2nd, and 3rd trimester of gestation and at postpartum and postlactation in 12 age-matched PGDM women, 9 GDM women, and 12 healthy control subjects. FPG and HbA1c were higher in every case in PGDM women than in control subjects, whereas in GDM patients, glucose was augmented only after parturition. FFA and p-hydroxybutyrate levels were higher in both PGDM and GDM patients than in control subjects during gestation but not after parturition. Total TGs and VLDL, LDL, and HDL TGs increased with gestational time in the three groups and declined at postpartum, and although total cholesterol and VLDL, LDL, and HDL cholesterol followed a similar trend their rise was less pronounced, and the decline after parturition was slower than that of the TGs in the three groups, with no difference among them. The VLDL TG/cholesterol ratio declined in the three groups at the 3rd gestational trimester, whereas in both LDL and HDL, the TG/cholesterol ratio, but not the cholesterol/phospholipid ratio, increased during gestation in the three groups, indicating a specific enrichment of TGs in these particles. The increase in apoA-I and apoB with gestation was parallel to the respective changes In HDL and LDL cholesterol and, again, no difference was observed between the three groups. Plasma levels of p-estradiol, progesterone, and prolactin increased sharply with gestation and declined at postpartum in the three groups, but absolute values of p-estradiol and prolactin, at the three trimesters of gestation, were lower in PGDM patients, but progesterone levels were lower than controls in GDM women only at the 3rd trimester. The logarithm for each of these hormones correlated linearly with VLDL, LDL, and HDL TGs, and the highest correlation coefficient value corresponded to the regression between p-estradiol and HDL TGs. Because estrogens are known to increase VLDL production, decrease hepatic lipase activity, and increase HDL TG levels, we propose that the decreased estradiol levels In our diabetic patients impede an exaggerated rise of circulating llpoproteins above the normal range. We also propose that the development or lack of development of a dyslipidemic condition in diabetic pregnancy depends on the balance between the metabolic control and the level of sex hormones.

To understand the mechanism responsible for maternal hyperlipidemia, 25 healthy pregnant women were studied longitudinally during the three trimesters of gestation and at post-partum, and 11 were studied again at post-lactation. Triglyceride and cholesterol levels increased with gestation in all the lipoprotein fractions. However, the greatest change appeared in low density (LDL) and high density (HDL) lipoproteins, both of which showed an increase in their triglyceride/ cholesterol ratio. The proportional distribution of HDL subfractions showed that the HDL2b fraction was the only one that increased with gestation, whereas both HDL.sa and HDLsb had the greatest decrease. Cholesteryl ester transfer protein activity increased during the second trimester of gestation. While postheparin lipoprotein lipase activity decreased during the third trimester, postheparin hepatic lipase activity progressively decreased from the first trimester. The 17J3-estradiol, progesterone, and prolactin hormones progressively increased from the first trimester of gestation. The lipoprotein-triglyceride values correlated linearly and negatively with the logarithm of either postheparin lipase activities, HDlrtriglycerides showing the highest correlation coefficient when plotted against the hepatic lipase values (r = -0.757). It appeared that the highest correlation between any of the HDL subclasses and the activity of the enzymes was for hepatic lipase activity versus HDL2b (r = -0.456) or HDLsa (r = 0.519). A significant lineal correlation also appeared between the postheparin hepatic lipase activity and the logarithm of any of the sex hormones studied, the highest value corresponding to estradiol (r = -0.783). Ill Therefore, during gestation, the effect of estrogen in enhancing very low density lipoprotein (VLDL) production and decreasing hepatic lipase activity plays a key role in the accumulation of triglycerides in lipoproteins of density higher than VLDL.

During the first two thirds of gestation, coinciding with a minimal accretion by the conceptus, the mother is in an anabolic state which is supported by her hyperphagia and the more efficient conservation of exogenous nutri~nts whenever she eats. During this phase maternal fat depots are accumulated thanks to the enhancement in adipose tissue lipogenic and glycerolgenic activity. In the latter part of gestation, on the contrary, the rapid fetal growth is sustained by the intense transfer of nutrients from maternal circulation. Glucose is quantitatively the most abundant of the different substrates that cross the placenta and despite enhanced maternal gluconeogenesis this transfer is the cause of the maternal tendency to hypoglucemia. This causes a switch to a net catabolic state which is specially evident in the net breakdown of fat depots. Enhanced release of adipose tissue lipolytiL- products, FFA and glycerol. facilitates the liver synthesis of triglycerides and their later release into circulation associated to VLDL. Glycerol is also used as an important ,, luconeogenic substrate and FFAs are hroken d~wn through 13-oxidation for ketone body synthesis. These pathwa/s become heightened when food is withheld and actively contribute to the availability of fuels to the fetus which becomes partially preserved from maternal metabolic insult. Enhanced liver production of VLDL triglycerides and decreased extrahepatic lipoprotein lipase contribute to exaggerated maternal hypertriglyceridemia which, besides being a floating metabolic reserve for emergency conditions such as starvation, constitutes an essential substrate for milk synthesis around parturition in preparation for lactation.