Increasing the cAMP level with the PDE4 inhibitor rolipram (Park et al., 2012) or roflumilast (Tikoo et al., 2014, Wouters et al., 2012) also activates AMPK and Sirt1 and protects against obesity and type 2 diabetes in mice and humans. The gene discussed is PRKAA2; the disease is obesity due to melanocortin 4 receptor deficiency.