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

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. Electronic supplementary material The online version of this article (10.1186/s12967-019-1980-6) contains supplementary material, which is available to authorized users.

Anti-ApoA-1 IgGs in Familial Hypercholesterolemia Display Paradoxical Associations with Lipid Profile and Promote Foam Cell Formation

“…We used a validated model of THP-1 monocytes cultured in RPMI 1640 medium supplemented with 10% FBS at 37 • C in 5% CO 2 [35]. To perform the experiments for passive diffusion, cells were seeded in 24-well plates at a density of 5 × 10 5 cells/well in the presence of 100 ng/mL PMA for 72 h to allow differentiation into macrophages.…”

“…Given the decrease in membrane free cholesterol induced by anti-ApoA-1 IgG in response to the ACAT redistribution within intracellular pools, we expected these antibodies to decrease passive diffusion due to the decrease in the free cholesterol gradient. For this purpose, we used a validated model of human macrophage derived from THP-1 monocytic cell line [35] as our human primary macrophage model was not validated for such kind of experiments. Cells were treated for 24 h with anti-ApoA 1 IgGs or control IgGs in the absence of serum but in presence of 0.2% albumin to avoid any active ABCA1-, ABCG1-or SR-B1-mediated cholesterol efflux.…”

MicroRNAs as the Promising Markers of Comorbidities in Childhood Obesity – A Systematic Review

“…Main characteristics of selected articles can be found in Table 2. Cholesterol efflux alterations in adolescent obesity: role of adiposederived extracellular vesical microRNAs [19] Barberio et al…”

The Art of Intercellular Wireless Communications: Exosomes in Heart Disease and Therapy

“…Recent studies suggest that adipocytes also secrete exosomes that play a critical role in obesity mediated metabolic disorders (Ying et al, 2017; Zhao et al, 2018). Interestingly, the majority of circulating exosomes are derived from adipose tissue and their content is determined by the health of the adipose tissue (Barberio et al, 2019). Adipose tissue biology is primarily regulated by the transcription factor PPAR-gamma and its agonists have been used for insulin sensitization in diabetic patients.…”