Our results indicate that as an effective BAT (as well as beige cell) activator, indirubin may have a protective effect on the prevention and treatment of obesity and related diseases, which involved in the up-regulation of UCP1 expression and enhancing the BAT activity and (or) inducing browning of sWAT, at least in part, via activation of PKA and p38MAPK signaling pathways. Here, UCP1 is linked to obesity due to melanocortin 4 receptor deficiency.