Maternal obesity and gestational diabetes (GDM) are conditions associated with increased placental glucose uptake and excessive fat accumulation in the fetus causing fetal overgrowth. We have previously shown that adipose tissue from GDM women secrets higher number of exosomes and positively correlates with fetal birthweight. These findings led us to hypothesise that adipose tissue derived exosomes (AT-exo) from GDM women may influence placenta nutrient uptake and be responsible for fetal overgrowth. In this study, we aimed to determine the effect of AT-exo on placental glucose and fatty acid uptake.
Human omental adipose tissue was obtained from women with GDM (n=9 lean; n=6 obese) and BMI-matched normal glucose tolerant (NGT) controls (n=9 lean; n=6 obese) at the time of term Caesarean section. Adipose tissue explants were performed and exosomes were isolated from conditioned media by differential centrifugation and characterised based on size distribution, protein markers and morphology. To determine the effect of AT-exo on placenta, trophoblast cells were isolated from fresh placenta (n= 6 patients). The effect of AT-exo on glucose and fatty acid uptake in human primary placental trophoblast cells was evaluated using 2-NBDG and BODIPY, respectively. Statistical analyses between the groups were conducted using one-way ANOVA and p<0.05 was considered significant.
AT-exo from both lean and obese women with GDM significantly increased placental glucose uptake compared to BMI-matched NGT women. There was no difference in placental glucose uptake between AT-exo obtained from lean or obese women in both NGT or GDM women. Interestingly, AT-exo from obese GDM and NGT women significantly reduced fatty acid uptake compared to AT-exo from lean GDM and NGT women, respectively.
In conclusion, maternal AT-exo involves in regulating placental nutrient uptake, which can have an impact on fetal growth.