Dynamic Regulation of Lipid Metabolism in the Placenta of in Vitro and in Vivo Models of Gestational Diabetes Mellitus

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.