For the first time in the context of obesity, we characterized the sIL-6R+/+ mouse model (21), an approach to simulate ADAM10/17 hyperactivation for the specific target protein IL-6R by a Cre-mediated deletion of the genetic sequence coding for transmembrane and intracellular domains that consequently lead to specific trans-signalling execution. This evidence concerns the gene ADAM10 and obesity due to melanocortin 4 receptor deficiency.