Placental metabolic profiling in gestational diabetes mellitus: An important role of fatty acids

Abstract

Aim Gestational diabetes mellitus (GDM) is the most common metabolic disorder during pregnancy. Accumulating studies have reported metabolites that are significantly associated with the development of GDM. However, studies on the metabolism of placenta, the most important organ of maternal‐fetal energy and material transport, are extremely rare. This study aimed to identify and discuss the relationship between differentially expressed metabolites (DEM) and clinical parameters of the mothers and newborns. Methods In this study, metabolites from 63 placenta tissues (32 GDM and 31 normal controls) were assayed by ultra‐performance liquid chromatography‐high resolution mass spectrometry (UPLC‐HRMS). Results A total of 1297 annotated metabolites were detected, of which 87 significantly different in GDM placenta. Lipids and lipid‐like molecules accounted for 62.1% of DEM as they were significantly enriched via the “biosynthesis of unsaturated fatty acids” and “fatty acid biosynthesis” pathways. Linoleic acid and α‐linolenic acid appeared to be good biomarkers for the prediction and diagnosis of GDM. In addition, the level of PC(14:0/18:0) was negatively correlated with neonatal weight. 14 metabolites significantly different in male and female offspring, with the most increase in female newborns. Conclusion Even if maternal blood glucose level is well controlled, there are still metabolic abnormalities in GDM. Lipids and lipid‐like molecules were the main differential metabolites, especially unsaturated fatty acids.

Sex-Dependent Regulation of Placental Oleic Acid and Palmitic Acid Metabolism by Maternal Glycemia and Associations with Birthweight

“…In the human in vivo study where 13 C-PA was administered alongside other 13 C-fatty acids, GDM was associated with increased total placental 13 C-PA lipid [ 40 ], consistent with our finding of generally positive associations between the amount of placental 13 C-PA lipids with 2 h glycemia. The levels of endogenous placental non-esterified palmitic acid are also increased in GDM compared to controls [ 41 ]. Obesity reportedly had no influence on total 13 C-OA placental lipid production in vitro [ 42 ] and GDM did not associate with any change in 13 C-OA placental lipids in vivo [ 40 ], consistent with our own results showing no association between BMI or glycemia and 13 C-OA placental lipids when sex was not considered.…”

A comparative lipidomic study of the human placenta from women with or without gestational diabetes mellitus

“…[22][23][24][25] Previous studies suggested that placental lipid profiles, for example, TAGs and phospholipids differed between women with or without GDM. 26,27 Thus, a systematic lipidomics analysis would shed light on the molecular basis of GDM and allow us to better understand its etiology. Therefore, we performed a lipidomics analysis to dissect the lipid profile alterations induced by GDM.…”

“…Yang Y et al compared metabolic profiles of placental lipids between women with or without GDM and confirmed that lipids and lipid-like molecules contribute to the main difference in metabolites, especially unsaturated fatty acids. 26 Another study specifically focused on the alterations of GP species in the placenta induced by GDM, and identified PC(16:0/20:4) as the major component to supply arachidonic acid for fetuses. 27 Consistent with these findings, we also found striking abnormalities in placental lipids of GDM patients and the dysregulated lipids were also mainly categorized to GPs such as PE and PC.…”

Dysregulation of Placental Lipid Hydrolysis by High-Fat/High-Cholesterol Feeding and Gestational Diabetes Mellitus in Mice

“…We have recently shown that the intracellular CE hydrolases LAL and HSL are expressed and active in the mouse placenta and that LAL deficiency leads to the disturbance of placental lipid metabolism [ 17 ]. Transcriptomics and metabolomics analyses revealed altered lipid metabolism in placental cells under high glucose conditions [ 18 ] and that placental lipids are the main metabolites with variable abundance in women with GDM [ 19 ]. Moreover, placental FA transporters were found to be upregulated in diabetic women [ 9 , 20 ].…”

“…Notably, the activity of these enzymes relies on posttranslational modifications and their lipolytic activities in GDM placentae are still unknown. In the human placenta, EL is dysregulated in pregnancies complicated by GDM [ 22 ], and placental lipid metabolism is altered due to an abnormal FA profile [ 18 , 19 , 23 , 24 ]. However, activity-based studies on intracellular lipases are still missing [ 25 ].…”