MDR knockout in male mice increased macrophage and T cell subpopulations and inflammatory markers specifically in visceral adipose tissue.
The lncRNA Dleu2 and miRNA15/16 cluster regulates intrinsic differences between visceral and subcutaneous adipose tissue at the progenitor stage, influencing macrophage polarization and insulin signaling.
Introduction and Objective: Obesity and diabetes have reached epidemic proportions over the past decade. However, the mechanisms underlying the depot-specific white adipose tissue associations with metabolic risks are not fully understood. Here, we investigated the role of a complex lncRNA Dleu2 which hosts miRNA15/16 cluster Dleu2 and miRNA15/16 together called minimal deleted region (MDR), in the depot-specific adipose tissue function. Methods: We performed a single-cell RNA sequencing of stromal vascular fraction from visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) of six-week-old WT and MDR knockout (MDR KO) male mice. Results: Cluster analysis using scGEATool, an ideal algorithm prototyping tool developed by us to facilitate scRNA-seq data analyses under Matlab settings, showed increased macrophage and T cells subpopulation in MDR KO-VAT and SAT compared to their WTs. Additionally, M1 macrophage population was significantly upregulated along with significantly decreased M2 macrophage in MDR KO-VAT. Subsequently, we observed significantly high TNF, IL1β, and IFNϒ expression only in MDR KO-VAT. We also observed a significant reduction in IRS2 and IGF1R expression in MDR KO-VAT with a non-significant decreasing trend in MDR KO-SAT, indicating dysregulated insulin signaling. Interestingly, we identified that stemness was significantly reduced only in MDR KO-VAT suggesting differential stem cell-mediated metabolic dysregulation. We are currently confirming our above findings as well as cellular interaction and pseudotime analysis using R Studio. Conclusion: Our data underscores lncRNA-miRNA cluster regulated intrinsic differences between VAT and SAT at progenitor stage which sets the foundation for an early therapeutic approach that is urgent and an unmet clinical need. Disclosure N. Shree: None. S. Gupta: None. J. Cai: None. M. Choudhury: None. Funding The Morris L. Lichtenstein, Jr. Foundation (M2000270)
SHREE et al. (Fri,) conducted a other in Obesity and diabetes. MDR knockout vs. Wild-type (WT) was evaluated on Adipose tissue cellular heterogeneity and gene expression. MDR knockout in male mice increased macrophage and T cell subpopulations and inflammatory markers specifically in visceral adipose tissue.