MC4R and Hyperinsulinemia: Indeed, the knockout of either SF-1 or any one of several components of the melanocortin system (e.g., β-endorphin, melanocortin-4 receptors) leads to hyperphagia, obesity, hyperleptinemia and hyperinsulinemia (Majdic et al., 2002; Appleyard et al., 2003; Cone, 2006).