Subcutaneous adipose tissue compensates for the perturbations in circulating one-carbon metabolism in women with gestational diabetes

The prevalence of gestational diabetes mellitus (GDM) is rising and poses important health risks for the mother, developing fetus and offspring, even when maternal glycemic control is well managed. This study aimed to identify the differently expressed metabolites (DEMs) in maternal plasma between GDM pregnancies with good glycemic control and healthy pregnancies, along with the DEMs-related metabolism in adipose tissue. Pregnant women with scheduled caesarean sections were recruited. Venous blood samples were collected on the day prior to delivery for targeted metabolomics analysis focusing on the 200 polar metabolites in central carbon metabolism. Subcutaneous and omental white adipose tissue (sWAT and oWAT) were harvested at delivery. A total of 162 metabolites were quantified, revealing 2 up-regulated (D-glucose 6-phosphate (G6P), succinate) and 8 down-regulated DEMs, which exhibited a fold change of ≥ 1.5 or ≤ 0.67, respectively. Among the down-regulated DEMs, 5 metabolites—pyridoxine, glycine, S-methyl-l-cysteine, methionine, and S-carboxymethyl-l-cysteine—are related to one-carbon metabolism (OCM). In response to perturbation in circulating OCM, boosted methionine cycle, NAD + metabolism, and adipogenesis were observed in sWAT of GDM subjects, with no changes detected in oWAT. None of the 10 DEMs correlates with either blood glucose or insulin, but showed significant correlations with TG, TC, LDL-C and HDL-C. The present study indicates that sWAT compensates for the perturbations in circulating OCM associated with GDM and targeting to the OCM may be an effective strategy to control the long-term metabolic risk of GDM offsprings.