Importantly, the AC5/SIRT1 regulation is unique to AC5, since our data show that AC5 KO is resistant to obesity [6], but AC6 KO did not affect body weight and SIRT1 expression [3] (Figure 3), and AC3 KO actually induced obesity [125]. This evidence concerns the gene ADCY3 and obesity due to melanocortin 4 receptor deficiency.