Resident macrophages in the adipose tissue produce cytokines, such as tumour growth factor (TGF)-β and tumour necrosis factor (TNF)-α, that also up-regulate PAI-1[37,38], indicating that the increase in PAI-1 occurs parallel to the obesity-induced development of T2DM. This evidence concerns the gene TGFB1 and obesity due to melanocortin 4 receptor deficiency.