Although the mechanisms by which obesity inhibits UCP1 expression remain unclear, a role of inflammation has recently been proposed, since integrin alpha 4 (ITGA4)- and VCAM-1 mediated macrophage-adipocyte interactions were found to inhibit UCP1 expression by ERK1/2 and p38 pathway blockade. This evidence concerns the gene MAPK3 and obesity due to melanocortin 4 receptor deficiency.