FNDC5 and obesity due to melanocortin 4 receptor deficiency: This is an important result to be reported, not only because it extends our knowledge about the different sources of irisin production (i.e., muscle/AT) and some mechanisms underlying the balance between WAT (energy storage) and BAT (energy expenditure) and adipocyte metabolism in obesity but also because it indirectly suggests that this adipo-myokine can act as a “signaling factor”, a messenger for interorgan crosstalk communication involving multiple endocrine organs in an orchestrated fashion, including muscle, AT, and bones.