Continuing efforts to delineate tissue specific mechanisms of GLP-1 action are necessary in order to identify novel translational alternatives and foster the development of new GLP-1-based therapeutic agents harnessing different aspects of GLP-1 biology with therapeutic potential not only for T2D and obesity, but also for heart, liver, kidney, lung and brain related disorders. Here, GLP1R is linked to obesity due to melanocortin 4 receptor deficiency.