The mice lacking IL-21 or mice with specific deletion of STAT3 in T cells fed with HFD showed an increase of VAT Treg cells and an improvement of adipose inflammation and insulin sensitivity, suggesting an important role for IL-21 and STAT3 signaling in regulating VAT Treg cells in obesity (63, 66). This evidence concerns the gene IL21 and obesity due to melanocortin 4 receptor deficiency.