22-LB: MiRNA Profiling of Exosomes Derived from Perivascular Adipocyte Tissue in Type 2 Diabetic Mice

Background: Exosomes (EXs), a major type of extracellular vesicles, are emerging as a novel type of intercellular communicators. MicroRNAs (miRs) are one of the major executors of EXs. The previous study shows that lean and obesity adipocyte tissue EXs could elicit different effects in response to insulin sensitivity, the underlying mechanism is related to their carried miRs. Given EX cargoes and function vary on their cellular status, we speculate the miR profiling of EXs derived from the perivascular adipose tissue (PVAT) is altered in diabetic conditions. Methods: EXs were isolated from the PVAT tissue of type 2 diabetic db/db and control db/c mice. EX size and concentration were analyzed by nanoparticle tracking analysis. The miR profiling of PVAT-EXs was analyzed by mmu-miR miRome profiling kit. The miRs of interest were further validated by qRT-PCR. Results: 1) The PVAT-EXs level was higher in diabetic db/db mice than that in non-diabetic db/c mice; 2) In db/db mice, exosomal miRs profile was changed. The exosomal miRs, miR-223, miR-181a, miR-146a, miR-34a, and miR-210, were either down-regulated or up-regulated > 3-fold when comparing that in db/c mice. Among these candidate miRs, miR-181a, miR-223, miR-210, and miR-146a might be involved in modulating adipose tissue inflammation and/or vascular function. MiR-34a could participate in white adipose tissue browning, macrophage polarization, and glucose tolerance. Conclusion: Our data have demonstrated that the miR profiling of PVAT-derived EXs is changed in type 2 diabetic conditions, which suggests the functions of these EXs might be altered in diabetic conditions. Disclosure S. Chen: None. V. Polaki: None. J. Bihl: None. J. Wang: None.