Proteomic Profile of Adipose Tissue-Derived Exosomes and Their Potential Role on Placental Glucose Metabolism in Gestational Diabetes Mellitus

Abstract

Emerging studies suggest that adipose tissue derived exosomes involves in regulating insulin action and glucose homeostasis. In this study, we hypothesised the protein content of adipose tissue derived exosomes (exo-AT) differs in normal glucose tolerant (NGT) and gestational diabetes mellitus (GDM) pregnancies which lead to changes in placental glucose metabolism. Human omental adipose tissue was obtained from GDM (n=60) and BMI-matched NGT (n=48) pregnancies at the time of term Caesarean section. Exosomes were isolated from tissue-conditioned media by differential centrifugation and characterised using nanoparticle tracking analysis and SWATH mass spectrometry. The effect of exosomes on human placental cells was evaluated using a Human Glucose Metabolism RT² Profiler PCR Array. The total number of exosomes (number of vesicles/mg adipose tissue/24 hour) were significantly higher in GDM compared to NGT. The number of exosomes positively correlated with maternal BMI and fetal weight. We identified 122 proteins upregulated in the exo-AT from GDM compared to NGT. Ingenuity pathway analysis revealed the upregulated proteins are associated with mitochondrial dysfunction and oxidative phosphorylation (OXPHOS). When compared to NGT exo-AT, GDM exo-AT increased ALDOB, PGK2 and GCK in placental cells. The data obtained in this study suggest that exosomes secreted from adipose tissue regulates placental glucose metabolism in GDM. Improving the communication of exo-AT to placental tissues may serve as an effective intervention strategy to prevent the consequences of GDM such as fetal overgrowth. Disclosure N. Jayabalan: None. V. Ormazabal: None. A. Lai: None. M. Lappas: None.