1. Cholesterol efflux alterations in adolescent obesity: role of adipose-derived extracellular vesical microRNAs.
- Author
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Barberio MD, Kasselman LJ, Playford MP, Epstein SB, Renna HA, Goldberg M, DeLeon J, Voloshyna I, Barlev A, Salama M, Ferrante SC, Nadler EP, Mehta N, Reiss AB, and Freishtat RJ
- Subjects
- Adolescent, Biological Transport, Circulating MicroRNA blood, Circulating MicroRNA genetics, Female, Humans, Lipoproteins blood, Macrophages metabolism, Male, MicroRNAs genetics, Pediatric Obesity blood, THP-1 Cells, Adipose Tissue metabolism, Cholesterol metabolism, Extracellular Vesicles genetics, MicroRNAs metabolism, Pediatric Obesity genetics
- 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/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., 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.- Published
- 2019
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