The decreased plasma levels of Adiponectin that in turn cause a decrease in AdipoRs levels in obesity, lead to insulin resistance and to a status of reduced Adiponectin sensitivity, the so-called “vicious cycle.” Independently of AMPK, Adiponectin stimulates a ceramidase activity associated with its two receptors, enhancing ceramide catabolism and formation of sphingosine-1-phosphate (S1P) (Holland. This evidence concerns the gene ADIPOQ and obesity due to melanocortin 4 receptor deficiency.