This new findings have following implications: 1) GHS-R signaling in BAT contributes to diet-induced obesity by suppressing thermogenesis; 2) The thermo-beneficial effect of GHS-R deficiency in BAT is diminished in the obese animals, suggesting that GHS-R mediated thermogenic signaling is impaired in obesity; 3) GHS-R antagonists likely activate thermogenesis under normal metabolic state but suppress thermogenesis under obese state, this differential effect must be taken into consideration in assessment of the therapeutic potential of GHS-R antagonism. Here, GHSR is linked to obesity due to melanocortin 4 receptor deficiency.