This may be in the heart of our inability to turn MCH into a valid pharmacological target to treat obesity or psychiatric disorders (Méndez-Andino and Wos, 2007; Högberg et al., 2012), as the desirable effects of MCHR1 antagonism are overshadowed by unwanted side effects. Here, MCHR1 is linked to obesity due to melanocortin 4 receptor deficiency.