Project description:Unlike visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) can play a protective role against the development of insulin resistance and metabolic dysfunction in obesity. These changes are associated with higher induction of pro-inflammatory programs and macrophage infiltration in VAT compared with SAT in obesity. Moreover, our results suggest that subcutaneous adipose tissue macrophages (ATMs) release small extracellular vesicles (sEVs) that can improve insulin sensitivity, opposite to the effect of visceral ATM sEVs in obesity. This functional difference was associated with changes in the proportion of resident ATMs, as well as proinflammatory, recruited ATMs. To study the mechanism by which adipose tissue inflammation and macrophage infiltration are differentially regulated in SAT vs VAT, we performed single cell RNA sequencing (scRNA-seq) analysis in sorted live CD45+ CD11b+ myeloid cells from stromal vascular fraction (SVCs) of SAT and VAT of mice fed normal chow diet, high fat diet, or SVCs of HFD mice after the diet switch from high fat diet to normal chow diet, or treatment with insulin sensitizing, rosiglitazone.