Gene expression of visceral adipose regulatory T cells from mice with specific deletion of insulin receptor in the cells

Visceral adipose tissue (VAT) regulatory T cells (Tregs) control inflammation and metabolism. Diet-induced obesity causes hyperinsulinemia and diminishes VAT Treg number and function, but whether these two phenomena were mechanistically linked was unknown. We hypothesized that excessive insulin signaling in obesity negatively impact VAT Tregs. Using Treg-specific insulin receptor deletion (Foxp3-cre;Insr-fl/fl) mice, we compared the gene expression of VAT Tregs from control and knockout mice in obesity and aging, two models of hyperinsulinemia. We found that genes associated with Treg functions were altered in Tregs lacking insulin receptor. Control (Foxp3-cre) and Treg-specific insulin receptor deletion (Foxp3-cre;Insr-fl/fl) male mice were fed either a high-fat diet (HFD) or normal chow diet (NCD) for 13 weeks, starting at 3 weeks old, to reach obesity and hyperinsulinemia. Alternatively, control and knockout mice were aged on NCD for 52 weeks to reach ageing-associated hyperinsulinemia. VAT Tregs were then isolated by fluorescence-activated cell sorting, and analyzed by a custom Nanostring mRNA panel.