Global knockout of the PKA regulatory subunits RIIβ (Prkar2b) (32), RIIα (Prkar2a) (33, 34), and the catalytic subunit beta (Prkacb) (35) in mice all caused distinct forms of diet-induced obesity resistance that conveyed a range of sex-dependent phenotypic characteristics. Here, PRKAR2B is linked to obesity due to melanocortin 4 receptor deficiency.