ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: Endocrinology 2017 Aug 1;158(8):2543-2555

Maternal obesity and gestational diabetes (GDM) are associated with a higher risk for maternal, and offspring complications and appear to be mediated at least partly by an aberrant placental morphology and function, with altered nutrient transport capacities. The human placenta adapts to mild maternal diabetes by limiting placental glucose transfer, and consequently protecting the fetus to a certain degree from excessive glucose exposure. In the maternal circulation, fatty acids are primarily transported in lipoproteins, which are not taken up by the placenta in an appreciable extent. Both placental lipoprotein lipase and endothelial lipase hydrolyze maternal plasma lipoprotein, triglycerides and phospholipids, and liberated FA can be taken up by the placenta. Non-esterified fatty acids can cross placental membranes through facilitated diffusion. This process is mediated by a family of transmembrane fatty acid transporters, fatty acid binding proteins, fatty acid translocase (FAT/CD36) and the MFSD2a transporter. Placental lipid content depends on maternal supply. Therefore, maternal dyslipidemia status may be expected to alter lipid composition in placental tissue. GDM alters the placental fatty acid content and the expression of genes involved on fatty acid transfer to the fetus.

To test the hypothesis that placental fatty acid oxidation capacity is impaired and fatty acid esterification is enhanced in obese women, this study assessed the following: (1) acylcarnitine profiles, lipid content, and expression of key components of fatty acid esterification and oxidation pathways in placentas of lean and obese women, and (2) [3 H]-palmitate oxidation and esterification in trophoblasts isolated from placentas of lean and obese women. The key finding was that maternal obesity is associated with an increase in lipid esterification and storage, and a decrease in mitochondrial fatty acid oxidation, which is compensated for by an upregulation of peroxisomal fatty acid oxidation. Altogether, these changes may serve to limit the amount of maternal lipid transferred to the fetus. Consistent with previous reports studies, lipid content was higher in placentas from obese as compared with lean women. PPARg, a lipid-activated transcription factor, regulates the expression of lipid esterification and storage genes in several tissues and this was upregulated in placentas of obese women. Placental fatty acid concentrations may be elevated in obese women due to either increased maternal supply, secondary to maternal insulin resistance and increased lipolysis, or lower placental FA oxidation. It is speculated that elevated fatty acid concentrations within the placenta activate PPARg. In turn, PPARg stimulates the transcription of DGAT1, SCD1, and ACC, key genes involved in lipid esterification and storage. Further studies are necessary to confirm this hypothesis in placental tissue, although others have described such a mechanism in adipose and hepatic tissues in mice and non pregnant subjects.