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

• Main Authors: Matthew D. Barberio, Lora J. Kasselman, Martin P. Playford, Samuel B. Epstein, Heather A. Renna, Madeleine Goldberg, Joshua DeLeon, Iryna Voloshyna, Ashley Barlev, Michael Salama, Sarah C. Ferrante, Evan P. Nadler, Nehal Mehta, Allison B. Reiss, Robert J. Freishtat
• Format: Article
• Language: English
• Published: BMC 2019-07-01
• Series: Journal of Translational Medicine
• Subjects: Extracellular vesicle; microRNAs; Obesity; Cholesterol Efflux
• Online Access: http://link.springer.com/article/10.1186/s12967-019-1980-6

Abstract Background Macrophage 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. Methods We 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/m2) 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. Results Efflux 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 μg/mL vs. 3 μg/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.