Furthermore, we demonstrated that the anti-obesity of hAMSCs-CM might be related to their multiple molecular mechanisms which were involved in activating AKT/GLUT4-mediated glucose metabolism, enhancing UCP1/PPARα-mediated energy expenditure, and increasing STAT3-ARG1-mediated M2 macrophage polarization during the development of obesity. Here, ARG1 is linked to obesity due to melanocortin 4 receptor deficiency.