Adipose tissue exosomal proteomic profile reveals a role on placenta glucose metabolism in gestational diabetes mellitus

Molecules produced by adipose tissue (AT) function as an endocrine link between maternal AT and fetal growth by regulating placental function in normal and gestational diabetes mellitus (GDM). We hypothesised that AT-derived exosomes from women with GDM carry a specific set of proteins that influences glucose metabolism in placenta. Exosomes were isolated from omental AT-conditioned media from pregnant women with normal glucose tolerance (exo-NGT, n=65) and women with GDM (exo-GDM, n=82). SWATH mass spectrometry (MS) was used to construct a small ion library from AT and exosomal proteins followed by ingenuity pathway analysis (IPA) to determine canonical pathways and biofunctions. The effect of exosomes on human placental cells was determined using a Human Glucose Metabolism RT2 Profiler PCR Array. The number of exosomes (vesicles/μg-tissue/24h) was significantly (1.7-fold) higher in GDM compared to NGT, and the number of exosomes positively correlated with birthweight Z score. IPA of the exosomal proteins revealed differential expression of the proteins targeting sirtuin (sirt) signalling pathway, oxidative phosphorylation (OXPHOS) and mechanistic target of rapamycin (mTOR) signalling pathways in GDM compared to NGT. Exo-GDM increased the expression of genes associated with glycolysis and gluconeogenesis in placental cells compared to the effect of exo-NGT. Our findings are consistent with the possibility that AT exosomes play an important role in mediating the changes in placental function in GDM, which may be responsible for some of the adverse consequences in this pregnancy complication, such as fetal overgrowth.