260-OR: Differences in Adipocyte Expandability and Function between Healthy Pregnancies and Pregnancies Complicated by Gestational Diabetes Mellitus and Preeclampsia

In obesity, failure of appropriate adipocyte expansion leads to ectopic fat deposition and systemic insulin resistance. Maternal obesity leads to higher incidence of gestational diabetes mellitus (GDM) and pre-eclampsia (PE), however adipocyte expansion is poorly characterised in pregnancy. This study aimed to compare adipocyte size, adipose tissue (AT) fibrosis, mRNA expression and insulin signaling in third trimester subcutaneous AT (SAT) and visceral AT (VAT) biopsies collected at Caesarean section from non-labouring GDM, PE and BMI- and age-matched healthy normotensive pregnant women (NT). SAT adipocyte diameter did not differ in complicated pregnancies compared to NT, however VAT diameter was higher in GDM (NT (n=30): 66.1±12.4 µm, GDM (n=30): 77.6±11.7 µm, p=0.001) but not PE (NT (n=7): 69.8±11.2 µm, PE (n=7) 72.4±8.9 µm, p=0.65). There was VAT hypertrophy in GDM (NT: 8.7±14.1% vs. GDM: 22.0±21.9% very large adipocytes, p=0.002) but not PE (NT: 13.7±21.3% vs. PE: 16.0±15.4%, p=0.67). Total fibrosis, assessed by picrosirius red staining of paraffin-embedded AT, was lower in GDM (NT (n=19): 45±13% area, GDM (n=12): 22±8%, PE (n=18): 45±12%, p<0.001); whereas pericellular fibrosis was higher in GDM (NT (n=18): 16±7%, GDM (n=12): 23±7%, PE (n=16): 15±4%, p=0.02). Higher HIF1A mRNA expression relative to PPIA was observed in GDM VAT (NT (n=11): 18.1±3.9%, GDM (n=11): 46.4±29.8%, PE (n=10): 25.3±3.6%, p=0.03). Lower insulin-stimulated phosphorylation of Akt was observed in GDM and PE SAT compared to NT by immunoblotting, yet did not reach significance (fold change in phospho-Akt:Akt NT (n=9): 43.1±70.1, GDM (n=7): 10.5±35.4, PE (n=5): 5.8±26.9 (p=0.19). These data suggest AT dysfunction in GDM with a phenotype typical of T2DM, whereas AT dysfunction in PE requires further elucidation.