Placental lipid transport and content in response to maternal overweight and gestational diabetes mellitus in human term placenta.

Background And Aims: Placental lipid transport is altered in women with high prepregnancy body mass index (pre-BMI) or gestational diabetes (GDM), which consequently affects foetal growth. However, the interaction of maternal overweight (OW) and GDM on placental lipid metabolism and possible adaptations are less studied. We aimed to examine whether maternal OW or GDM is the main factor disrupting placental lipid processing in human term placenta.

Methods And Results: A total of 152 lean (18.5 ≤ pre-BMI ≤ 23.9 kg/m) and OW (24 ≤ pre-BMI ≤ 27.9 kg/m) pregnant women with or without GDM with a scheduled delivery by caesarean section were recruited. Maternal venous blood samples were used to measure metabolic parameters during pregnancy. Term placentas and cord blood were collected at delivery to determine placental lipid metabolism and foetal circulating lipid levels. Maternal OW significantly increased the placental mRNA expression of genes involved in lipid metabolism (FAT/CD36, FATP1, FATP4, FATP6, and PPAR-α), elevated placental lipid content (triglyceride, cholesterol), enhanced placental mTORC1-rpS6 and ERK1/2 signalling, increased cord blood insulin levels and birth weight. Neonatal birth weight was positively correlated with maternal pre-BMI, placental ERK1/2 signalling and cord blood insulin. There was an interaction between OW and GDM in regulating key placental fuel transport and storage gene expression (LPL, FATP6, FABP7, PPAR-α, PPAR-β, PPAR-γ, IR-β, GLUT1, SNAT2, SNAT4, and LAT1).

Conclusion: Maternal OW mainly affects placental lipid metabolism, which may contribute to foetal overgrowth and may impact long-term offspring health. GDM plays a less significant role in affecting placental lipid transfer and other mechanisms may be involved.