LEP and hydrops fetalis: We demonstrated that long-term activation of MC4R using melanotan II (MTII), an MC4R agonist, recapitulates the cardioprotective effect of leptin after MI (Figs. 1a and 1c), and that genetic disruption of MC4R markedly attenuated or abolished leptin’s ability to improve cardiac metabolism and function after MI-induced HF (Fig. 1d) [27].