Cholesterol efflux alterations in adolescent obesity: role of adipose-derived extracellular vesical microRNAs

BackgroundMacrophage cholesterol efflux capacity has been identified as a predictor for cardiovascular disease. We assessed the relationship between adipocyte-derived extracellular vesicle microRNAs and macrophage cholesterol efflux capacity.MethodsWe assessed an adolescent cohort (n=93, Age, median (IQR)=17 (3)year, Female=71, Male=22) throughout the BMI continuum (BMI=45.2 (13.2) kg/m(2)) for: (1) cholesterol efflux capacity and lipoprotein profiles; (2) adipocyte-derived extracellular vesicle microRNAs in serum; (3) the role of visceral adipose tissue extracellular vesicle in regulation of cholesterol efflux and cholesterol efflux gene expression in THP-1 macrophages in vitro.ResultsEfflux capacity was significantly associated with HDL (r=0.30, p=0.01) and LDL (r=0.33, p=0.005) particle size. Multivariate-analysis identified six microRNAs associated (p<0.05) with cholesterol efflux capacity: miR-3129-5p (Beta=0.695), miR-20b (0.430), miR9-5p (0.111), miR-320d (-0.190), miR301a-5p (0.042), miR-155-5p (0.004). In response to increasing concentrations (1 mu g/mL vs. 3 mu g/mL) of VAT extracellular vesicle, cholesterol efflux (66%10% vs. 49%+/- 2%; p<0.01) and expression of ABCA1 (FC=1.9 +/- 0.8 vs 0.5 +/- 0.2; p<0.001), CD36 (0.7 +/- 0.4 vs. 2.1 +/- 0.8, p=0.02), CYP27A1 (1.4 +/- 0.4 vs. 0.9 +/- 0.5; p<0.05), and LXRA (1.8 +/- 1.1 vs. 0.5 +/- 0.2; p<0.05) was altered in THP-1 cells in vitro.Conclusion Adipocyte-derived extracellular vesicle microRNAs may, in part, be involved macrophage cholesterol efflux regulation.