The effect of high glucose on lipid metabolism in the human placenta

Abstract

Diabetes mellitus (DM) during pregnancy can result in fetal overgrowth, likely due to placental dysfunction, which has health consequences for the infant. Here we test our prediction from previous work using a placental cell line that high glucose concentrations affect placental lipid metabolism. Placentas from women with type 1 (n = 13), type 2 (n = 6) or gestational (n = 12) DM, BMI-matched to mothers without DM (n = 18), were analysed for lipase and fatty acid transport proteins and fatty acid and triglyceride content. Explants from uncomplicated pregnancies (n = 6) cultured in physiological or high glucose were similarly analysed. High glucose levels did not alter placental lipase or transporter expression or the profile and abundance of fatty acids, but triglyceride levels were higher (p < 0.05), suggesting reduced β- oxidation. DM did not affect placental protein expression or fatty acid profile. Triglyceride levels of placentas from mothers with pre-existing DM were similar to controls, but higher in obese women with gestational DM. Maternal hyperglycemia may not affect placental fatty acid uptake and transport. However, placental β-oxidation is affected by high glucose and reduced in a subset of women with DM. Abnormal placental lipid metabolism could contribute to increased maternal-fetal lipid transfer and excess fetal growth in some DM pregnancies.

Contribution of gestational diabetes mellitus heterogeneity and prepregnancy body mass index to large‐for‐gestational‐age infants—A retrospective case‐control study

“…In addition, the elevated maternal insulin levels promote placental amino acid transport from the mother to the fetus, which in turn increase the risk of excessive fetal growth in these pregnancies 26 . Moreover, maternal blood lipid metabolism disorders might affect placental lipid transfer, which results in increased maternal‐fetal lipid transport and excessive fetal growth in women with GDM‐resistance 27 . In women with GDM dysfunction, the principal reason for fetal overgrowth was hyperglycemia.…”

Hyperglycemia and gestational diabetes suppress placental glycolysis and mitochondrial function and alter lipid processing

“…Understanding their separate roles is particularly important because they may contribute differently to the pathological compromises made by the placenta among pregnant persons with GDM. At present, hyperglycemia has not been shown to affect fatty acid uptake in pregnancies complicated by pre‐existing diabetes but is positively associated with placental triglyceride levels 20 . The degree to which CTB and SCT are independently affected by high maternal blood glucose levels has not been investigated.…”

LncRNA XIST serves as a diagnostic biomarker in gestational diabetes mellitus and its regulatory effect on trophoblast cell via miR-497-5p/FOXO1 axis

“…The children of GDM patients have a raised future risk of undergoing inflammation reaction, obesity, hypothalamus dysplasia, hyperactivity disorder, and neuropsychiatric morbidity (5)(6)(7)(8). High glucose may induce the dysfunction of the placenta, which in turn affects fetal health and even leads to fetal death (9,10). The normalization and stabilization of placenta and trophoblastic cells were fundamental in the duration of pregnancy for the health of unborn fetuses (11).…”