Going into labor and beyond: phospholipase A2 in pregnancy.

The phospholipase A2 (PLA2) family is a very diverse group of enzymes, all serving in the cleavage of phospholipids, thereby releasing high amounts of arachidonic acid (AA) and lysophospholipids. AA serves as a substrate for prostaglandin production, which is of special importance in pregnancy for the onset of parturition. Novel research demonstrates that PLA2 action affects the immune response of the mother toward the child and is therefore probably implied in the tolerance of the fetus and prevention of miscarriage. This review presents data on the biochemical and enzymatic properties of PLA2 during gestation with a special emphasis on its role for the placental function and development of the fetus. We also critically discuss the possible pathophysiological significance of PLA2 alterations and its possible functional consequences. These alterations are often associated with pregnancy pathologies such as preeclampsia and villitis or pregnancy complications such as obesity and diabetes in the mother as well as preterm onset of labor.

Gestational diabetes mellitus modulates neonatal high-density lipoprotein composition and its functional heterogeneity.

Gestational diabetes mellitus (GDM) is related to neonatal macrosomia and an increased risk of vascular events. We hypothesized that GDM exerts qualitative effects on neonatal high-density lipoprotein (HDL). HDL was isolated from control (n=11) and GDM maternal/neonatal donors (n=9) and subjected to shotgun proteomics. Differences in HDL mobility were assessed by FPLC and native gel-electrophoresis. Paraoxonase (PON1) activity, cholesterol ester-transfer protein (CETP) mass and activity, phospholipid, triglyceride and cholesterol concentrations were quantified with commercial kits. Total anti-oxidative capacity and cholesterol efflux capability of HDLs were measured. Four proteins involved in lipid metabolism, inflammation and innate immunity were differentially expressed between controls and GDM neonates. ApoM (decreased, p<0.05) and SAA1 (increased, p<0.05) showed the same differences on both, maternal and neonatal GDM HDL. Lower PON1 protein expression was corroborated by lower activity (p<0.05) which in turn was associated with attenuated anti-oxidant capacity of GDM HDL. Protein changes were accompanied by increased levels of triglycerides and decreased levels of cholesterol esters, respectively. The observed differences in GDM HDL lipid moiety may be related to CETP mass and activity alterations. The rate of cholesterol efflux from term trophoblasts to maternal and from placental endothelial cells to neonatal GDM HDL was impaired (p<0.05). In conclusion, GDM causes changes in HDL composition and is intimately associated with impaired cholesterol efflux capability as well as diminished anti-oxidative particle properties. Remodeling of neonatal GDM HDL in utero supports the hypothesis that maternal conditions in pregnancy impact neonatal lipoprotein metabolism.

Enzymes involved in hepatic acylglycerol metabolism in the chicken.

In laying hens, massive hepatic mobilization of fatty acids is required for the synthesis of oocyte-targeted very-low density lipoproteins (VLDL). The current study aims at identification of enzymes that hydrolyze hepatic acylglycerol stores regulated in a fashion compatible with supporting enhanced VLDL synthesis. We show that unlike mammals, chickens express adipose triglyceride lipase (ATGL) also in liver, where it is upregulated by fasting, while the enzyme patatin-like phospholipase domain-containing lipase 3 (PNPLA3) is suppressed. For the first time in any system, we show that hepatic arylacetamide deacetylase (AADA) is upregulated by fasting, and that its affinity for an insoluble carboxylester substrate is compatible with an in-vivo function similar to that of ATGL. Unknown heretofore, hepatic expression of chicken AADA is estrogen-responsive, and is induced to the same degree as the stimulation of VLDL-production by estrogen. These observations support roles of chicken ATGL, PNPLA3, and AADA in acylglycerol metabolism related to the high rates of VLDL synthesis that are essential for reproduction.