Lipoprotein Metabolism in Pregnancy, Fat Transport to the Fetus, and the Effects of Diabetes

Abstract

The objective of this paper is to review the extent and mechanisms of lipoprotein alterations in pregnancy, present new data relating to placental lipid transport in. normal humans and diabetic animals and consider possible effects on fetal growth and development in normal and diabetic pregnancy. The concentration of all lipoprotein fractions increases during pregnancy. VLDL cholesterol and triglyceride increase 2.5-fold over prepregnancy levels and LDL cholesterol increases 1.6-fold, all with peak levels at term. HDL cholesterol is maximally increased in midgestation by 1.45-fold and subsequently declines to 1.15-fold at term. The mechanisms of these lipoprotein changes have not been studied in humans but the hypertriglyceridemia in animal models is related to enhanced VLDL entry into the circulation. In addition, diminished adipose tissue lipoprotein lipase (LPL) activity in late gestation may cause a rerouting of triglyceride fatty acids to other tissues such as muscle and uterus for oxidation, rather than storage, since triglyceride transport is not reduced in pregnancy. All of these changes appear to be sex hormone mediated. In diabetic pregnancies, the available data indicate that triglyceride concentrations are increased and HDL cholesterol concentrations are decreased with reference to lipoproteins in nondiabetic pregnant women. Previously unpublished data show that a transplacental FFA gradient exists across the umbilical circulation in the direction of the fetus and is proportional to the maternal FFA concentration. No gradient is seen for triglyceride or total plasma cholesterol. However, transport of unmeasured amounts of triglyceride fatty acids may still occur via placental LPL and be exaggerated in diabetes where LPL declines in adipose tissue but not in placenta. The mechanism of transplacental cholesterol transport remains to be defined. Preliminary studies suggest that it depends on HDL as well as LDL since both can provide cholesterol for placental progesterone synthesis. In addition, fetal weight and length are associated with maternal apoproteins A-I and A-II, both major apoproteins of HDL. By lowering HDL in pregnancy, diabetes mellitus could negatively affect these relationships. In conclusion, sex hormone mediated modifications of lipoprotein physiology are described in pregnancy which may enhance triglyceride fatty acid transport to muscle for oxidation and LDL and HDL cholesterol delivery to growing maternal and fetal tissues, a process that diabetes could globally disrupt.

Study of serum lipid profile in pregnancy induced hypertension

“…The VLDL-C level, as reported by some researchers, might rise upto 2.5 folds at term over the pre-pregnancy level (15,16). VLDL level further increase in PIH as evidenced in the present study in corroboration with those of other workers (9,10,15), perhaps due to increased VLDL lipoproteins which accumulate over the maternal vascular endothelium, particularly those of uterine and renal vessels (17).…”

Effect of Pregnancy on the Lipid Profile in Egyptian Women

“…In present study, serum VLDL-C level rose significantly (P<0.05) in the third trimester of pregnancy in comparison to non-pregnant women, which is perhaps due to hypertriglyceridemia leading to enhanced entry of VLDL that carries endogenous triglyceride into circulation. These results are in accordance with Teichmann et al, (17) &Knopp et al, (18) and Potter and Netel, (19) whom reported that VLDL-C might rise up to 2.5 folds at term over the pre-pregnancy level.…”

Long-term effect of maternal obesity on pancreatic beta cells of offspring: reduced beta cell adaptation to high glucose and high-fat diet challenges in adult female mouse offspring

“…Obesity is associated with abnormalities of lipid metabolism [30]. Maternal non-estirified fatty acids can cross the placenta, and placental lipoprotein lipase hydrolyses triglycerides to fatty acids that can cross the placenta [31,32]. Thus, increased serum levels of maternal fatty acids and triglycerides may increase fatty acid transfer to the fetus.…”