Human placental lipid content and lipid metabolic enzyme abundance in obesity and across gestation

Abstract

Changes in placental lipid metabolism influence the delivery of lipids critical for fetal development and fetal requirements for lipids change across gestation. We hypothesized that placental lipid content and metabolic enzyme protein levels increase across gestation and are elevated in obesity. Placentas (4-40 weeks gestation) were collected from control (body mass index, BMI 18.5-24.9, n=37) and obese (BMI>30, n=19) pregnant women. Trophoblast villous tissue was homogenized and subjected to LC-MS/MS for phospholipid and triacylglycerol (TAG) analysis and western blot for protein quantification. The placental content of TAG species and 9 of 35 identified phosphatidylcholines (PC) were significantly higher (P<0.05) in first trimester (28-79%, 10-47%, respectively). Further, two TAG and three PC differed by maternal BMI and were significantly increased (P<0.05) in the obese group in first trimester (72-87%, 88-119%, respectively). Placental protein abundance of GPAT3 and AGPAT2, involved in de novo synthesis of PC and TAG, were higher (P<0.05) in the first trimester (66% and 74%, respectively). The protein abundance of the PC remodeling enzyme PLA2G4c was also higher (63%) in first trimester (P<0.05). In conclusion, the placental content of many phospholipid and TAG species and the protein level of associated synthesis enzymes are higher in first trimester human placenta. The high PC content may be related to the rapid membrane expansion in early pregnancy and the low placental oxygen tension may promote the accumulation of tissue TAGs in first trimester. Maternal obesity had only limited impact on placental lipid content and metabolic enzyme protein abundance.

Fetal sex differences in placental LCPUFA ether and plasmalogen phosphatidylethanolamine and phosphatidylcholine contents in pregnancies complicated by obesity

“…After electrophoresis and transfer onto a PVDF membrane (Bio-Rad Laboratories Inc.), we stained for total protein using Amido Black Stain (Sigma-Aldrich). Incubation of primary antibody LysoPhosphatidylCholine Acyl Transferase 4 (LPCAT4), PhosphoLipase A 2 Group IVC (PLA 2 G4C or iPLA 2 ) and 1-acylglycerol-3-phosphate O-acyltransferase 4 (AGPAT4) was carried out overnight at 4 °C (details on primary antibodies are provided in Additional file 1 : Table S2), and secondary antibody (peroxidase labeled anti-Rabbit IgG, diluted 1:3000, Cell Signaling Technology (Danvers, MA)) for 1 h at room temperature as previously depicted [ 35 ]. Immunolabeling was made visible with SuperSignal West Pico Plus detection solution (Thermo Scientific) in a G:Box ChemiXL1.4 (SynGene, Cambridge, UK).…”

“…One study has observed increased plasma ether PC containing DHA (PC O-16:0_22:6) in healthy women at 26–28 weeks of pregnancy compared to postnatal 4–5 years after delivery [ 18 ]. We have recently identified some ether linked phospholipid species in human placenta across gestation and found PE containing LCPUFA, such as PE O-16:1_22:6 and PE O-16:1_20:4, are enhanced in the third trimester compared to the first and second trimesters [ 35 ]. These data suggest a potential implication of those phospholipids in the placental LCPUFA metabolism and transfer to the fetus.…”

The importance of placental lipid metabolism across gestation in obese and non-obese pregnancies

“…In this issue of Clinical Science , Bidne et al have been able to surmount this challenge to examine human placentas and cord blood ranging from 4 to 40 weeks gestation [ 23 ]. Their study builds upon previous work detailing placental nutrient transporters across gestation [ 24 ] by quantifying lipid fractions, transporters, and metabolic pathways in first, second, and third trimester placenta, then comparing these levels between obese and non-obese pregnant women.…”

“…Acyl-transferase enzymes like glycerol-3-phosphate acyltransferase (GPAT) and 1-acylglycerol-3-phosphate-O-acyltransferases (AGPAT2 and AGPAT4) in the Kennedy Pathway and phospholipase A2 (PLA2G4c) and lysophosphatidylcholine acyltransferase (LPCAT4) in the Lands’ cycle remodel the fatty acid species being transported to the fetus. These elements of lipid metabolism in the placenta can be studied over gestation as well as between control and obese pregnancies to determine the mechanisms driving this important element of fuel transport, as demonstrated by Bidne et al [ 23 ] in this issue of Clinical Science . Created with BioRender.com.…”

“…As the fields of reproductive health and developmental origins of health and disease look to the placenta for answers regarding the role of fuels in driving pregnancy and fetal outcomes [1], it will be essential to overcome gaps in knowledge about adaptations in placental lipid metabolism across critical windows of and lysophosphatidylcholine acyltransferase (LPCAT4) in the Lands' cycle remodel the fatty acid species being transported to the fetus. These elements of lipid metabolism in the placenta can be studied over gestation as well as between control and obese pregnancies to determine the mechanisms driving this important element of fuel transport, as demonstrated by Bidne et al [23] in this issue of Clinical Science. Created with BioRender.com.…”