Placental Accumulation of Triacylglycerols in Gestational Diabetes Mellitus and Its Association with Altered Fetal Growth are Related to the Differential Expressions of Proteins of Lipid Metabolism

Author(s):  
Manoharan Balachandiran ◽  
Zachariah Bobby ◽  
Gowri Dorairajan ◽  
Sajini Elizabeth Jacob ◽  
Victorraj Gladwin ◽  
...  

Abstract Introduction Gestational diabetes mellitus (GDM) exhibit altered placental lipid metabolism. The molecular basis of this altered metabolism is not clear. Altered placental expression of proteins of lipogenesis and fatty acid oxidation may be involved in the placental accumulation of triacylglycerols (TG). The present study was aimed at investigating the differential expressions of placental proteins related to lipid metabolism among GDM women in comparison with control pregnant women (CPW) and to correlate them with maternal and fetal lipid parameters as well as altered fetal growth. Materials and Methods Maternal blood, cord blood, and placental samples were collected from GDM and CPW. The biochemical parameters, glucose, lipid profile and free fatty acids (FFA) were measured. The placental TG content was measured. Differential placental expressions of proteins; phosphatidylinositol-3-kinase (PI3K) p85α, PI3K p110α,liver X receptor alpha (LXRα), sterol regulatory element binding protein1(SREBP1), fatty acid synthase (FAS), stearyl CoA desaturase1 (SCD1), lipoprotein lipase (LPL),Peroxisome proliferator-activated receptor (PPAR)α and PPARγ were analysed by western blotting and immunohistochemistry. Results Placental protein expressions of PI3K p110α, LXRα, FAS, SCD1, and LPL were found to be significantly higher, whereas PPARα and PPARγ were lower in GDM women compared with CPW. The placental TG content and cord plasma FFA were increased in GDM women compared with CPW. The placental TG content positively correlated with Ponderal index of GDM new-borns. Conclusion Differential expressions of placental proteins related to lipid metabolism in GDM might have led to placental TG accumulation. This might have contributed to the fetal overgrowth in GDM.

2022 ◽  
Author(s):  
So Young Kim ◽  
Young Joo Lee ◽  
Sung-Min An ◽  
Min Jae Kim ◽  
Jea Sic Jeong ◽  
...  

Abstract Background: The purpose of this study was to investigate lipid metabolism in the placenta of Gestational diabetes mellitus (GDM) individuals and to evaluate its effect on the fetus. Methods: We examined the expression of lipogenesis- and lipolysis-related proteins in the in vitro and in vivo GDM placenta models. Results: The levels of sterol regulatory element binding protein-1c (SREBP-1c) were increased, and fat accumulated more during early hyperglycemia, indicating that lipogenesis was stimulated. When hyperglycemia was further extended, lipolysis was activated due to the phosphorylation of hormone-sensitive lipase (HSL) and expression of adipose triglyceride lipase (ATGL). In the animal model of GDM and in the placenta of GDM patients during the extended stage of GDM, the expression of SREBP-1c decreased and the deposition of fat increased. Similar to the results obtained in the in vitro study, lipolysis was enhanced in the animal and human placenta of extended GDM. Conclusion: These results suggest that fat synthesis may be stimulated by lipogenesis in the placenta when the blood glucose level is high. Subsequently, the accumulated fat can be degraded by lipolysis and more fat and its metabolites can be delivered to the fetus when the GDM condition is extended at the late stage of gestation. Imbalanced fat metabolism in the placenta and fetus of GDM patients can cause metabolic complications in the fetus, including fetal macrosomia, obesity, and type 2 diabetes mellitus.


2021 ◽  
Vol 224 (2) ◽  
pp. S455-S456
Author(s):  
Alexandra Mahdasian-Miller ◽  
Christina Scifres ◽  
David M. Haas ◽  
William A. Grobman ◽  
Robert M. Silver ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Linbo Guan ◽  
Ping Fan ◽  
Xinghui Liu ◽  
Mi Zhou ◽  
Yujie Wu ◽  
...  

BackgroundGALNT2 is a GalNAc transferase that regulates serum lipid fractions, insulin signaling, and lipogenesis. Genetic variants are implicated in the pathogenesis of gestational diabetes mellitus (GDM). The objective of this study was to investigate the association of GALNT2 rs2144300 and rs4846914 single nucleotide polymorphisms (SNPs) with the risk of GDM and related traits.MethodsTwo SNPs were genotyped, and clinical and metabolic parameters were determined in 461 GDM patients and 626 control subjects. Genetic associations with related traits were also analyzed.ResultsThe genotype distributions of the two SNPs in GDM patients were similar to those in normal controls. However, significant differences were noted across the three groups of genotypes with respect to the examined variables in subjects in a BMI-dependent manner. The rs4846914 and rs2144300 SNPs of GALNT2 were significantly associated with systolic blood pressure and/or diastolic blood pressure levels in nonobese GDM patients and atherogenic index (AI) in overweight/obese GDM patients. The rs4846914 SNP was also associated with fetal growth in overweight/obese GDM patients, and apo A1 and pregnancy weight gain in overweight/obese control women (all P<0.05).ConclusionsThe two polymorphisms in the GALNT2 gene are associated with variations in blood pressure, atherogenic index, and fetal growth in GDM, depending on BMI, but not with GDM. Our findings highlight a link between related phenotypes in GDM mothers and their fetuses and the genetic components.


Diabetologia ◽  
2018 ◽  
Vol 61 (12) ◽  
pp. 2528-2538 ◽  
Author(s):  
Lise L. Kurtzhals ◽  
Sidse K. Nørgaard ◽  
Anna L. Secher ◽  
Vibeke L. Nichum ◽  
Helle Ronneby ◽  
...  

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